A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Clinical Trial With KH176

SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)

Time Frame: Baseline, 1, 2, 4, 6, 8, 12, 24 hours, 7 day follow up

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group

Time Frame: Baseline (pre-dose Day 1), 24 h postdose, FU (7 days after last dosing)

Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD

Time Frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)

Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Pharmacodynamics of KH176

Time Frame: Day 1, day 7

Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group)

Time Frame: Baseline (pre-dose Day1), 24h post dose, FU (7 days after last dosing)

Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days after last dosing)

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD

Time Frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

MAD: Change From Baseline in ECG Results by Time Point: QTcF

Time Frame: Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple-dose part. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Relationship to Study Drug and Severity of Treatment-emergent Adverse Events

Time Frame: 4 months

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h, FU (7 days post-dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value ateach timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD

Time Frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated time points for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each time point are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group

Time Frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group

Time Frame: Baseline (pre-dose Day1), Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Phospholipidosis

Time Frame: Day 1, Day 7

Change from Day 1 to Day 7 in di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP) and normalized di-22:6-BMP (urine) - MAD

MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)

Time Frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.

Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD

Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD

Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group

Time Frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)

Time Frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.

SAD: Change From Baseline in ECG Results by Time Point: QRS Interval

Time Frame: Pre-dose, Day 1, Day 7

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.

SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval

Time Frame: Pre-dose, Day1, Day 7

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.

Maximum Concentration (Cmax) of KH176: SAD Group

Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group

Time Frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Cmax was obtained directly from the concentration-time data.

Maximum Concentration (Cmax) of KH176: MAD

Time Frame: pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group

Time Frame: pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group

Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

SAD: Change From Baseline in ECG Results by Time Point: PQ Interval

Time Frame: Pre-dose, Day 1, Day 7

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.

Terminal Elimination Half-life (T1/2) of KH183: SAD

Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.

Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD

Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.

Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group

Time Frame: pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

KH183: Percentage of Administered Dose Excreted in Urine: SAD

Time Frame: 24 hours post-dose

Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

KH183: Percentage of Administered Dose Excreted in Urine: MAD

Time Frame: Post dose Day 7

Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD

Time Frame: Day 7 Post dose

Urine concentrations of KH176 and KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)

Time Frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the PQ interval the average of the 3 recordings will be taken as baseline.

MAD: Change From Baseline in ECG Results by Time Point: QT Interval

Time Frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.

Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group

Time Frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. tmax was obtained directly from the concentration-time data.

Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group

Time Frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Accumulation factor was calculated as follows: AUCtau day 7/ AUCtau day 1.

Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD

Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.

KH176: Percentage of Administered Dose Excreted in Urine: SAD

Time Frame: 24 hours post-dose

Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD

Time Frame: 24 hours post-dose

Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group

Time Frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

SAD: Change From Baseline in ECG Results by Time Point: QT Interval

Time Frame: Pre-dose, Day 1, Day 7

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.

Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group

Time Frame: Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. Racc was calculated as follows: AUCtau day 7/ AUCtau day 1.

Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group:

Time Frame: Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group

Time Frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD

Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.

KH176: Percentage of Administered Dose Excreted in Urine: MAD

Time Frame: Day 7 post dose

Urine concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD

Time Frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.