A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Emicizumab in Healthy Chinese Volunteers

Phase 1

Completed

Conditions: Hemophilia A
Healthy Volunteers

Interventions: Drug: Emicizumab

Registration Number: NCT03380780

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This single-center, open-label study will evaluate the pharmacokinetics, safety, and tolerability of emicizumab following a single subcutaneous (SC) administration to healthy Chinese subjects.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 16

Inclusion Criteria

Healthy Chinese male subjects, aged 20-45 years inclusive at the time of screening
Chinese subjects must have Chinese parents and grandparents, all of whom were born in China
A body mass index (BMI) between 19 and 24 kilograms per height in meters squared (kg/m^2), inclusive
Able to participate and willing to give written informed consent and to comply with the study requirements

Exclusion Criteria

Any history or presence of a clinically significant disorder, or any other condition or disease which in the judgement of the investigator would place the subject at undue risk; interfere with absorption, distribution, metabolism, and excretion of emicizumab; or interfere with the ability of the subject to complete the study
Major illness within 1 month prior to dosing, and/or any condition which could relapse during or immediately after the study
Use of any prescribed or over-the-counter (OTC) medication or herbal medicine taken within 14 days prior to dosing or within 5 times the elimination half-life of the medication prior to dosing (whichever is longer), with some exceptions
Any significant donation/loss of blood or plasma (greater than 450 milliliters) within the 3 months prior to dosing
Regular smoker with consumption of more than 10 cigarettes per day or the equivalent amount of tobacco
Participation within a clinical study with an investigational drug or device within the last 3 months prior to dosing
Any clinically relevant history of hypersensitivity or allergic reactions, either spontaneous or following drug administration or exposure to foods or environmental agents
Previous or concomitant thromboembolic disease such as deep vein thrombosis (DVT) or signs of thromboembolic disease, or family history of thromboembolic disorder such as serious DVT
At high risk for thrombotic microangiopathy (e.g., have a previous medical or family history of thrombotic microangiopathy), in the investigator's judgment
Previous or concomitant autoimmune or connective tissue disease
History of tuberculosis or active tuberculosis with positive test result at screening
Any other reason that, in the judgment of the investigator, would render the subject unsuitable for study participation

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Emicizumab	Emicizumab	-

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) of Emicizumab	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.
Area Under the Plasma Concentration Versus Time Curve (AUC) Between Time Zero Extrapolated to Infinity (AUC0-inf) of Emicizumab	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes, Absolute Count	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Total Neutrophils, Absolute Count	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Number of Participants by Test Results for Blood in Urine by Timepoint	Baseline and Days 2, 8, 29, 57, 85, and 113	Urine samples were collected from participants at the indicated timepoints for evaluation of urinalysis parameters. The number of participants with test results for blood in urine of 0 (Absent), +1 (Trace), +2 (Positive), and +3/+4 (Strong Positive) at baseline and each timepoint are reported. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Vital Signs by Timepoint: Diastolic Blood Pressure	Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Platelet Count	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in ECG Results by Timepoint: QTcB Duration (Bazett's Correction Formula)	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
Number of Participants With Concomitant Medications	From screening to study completion (20 weeks)	The original terms recorded by the investigator for concomitant medications were standardized by the sponsor by assigning preferred terms. The duration of treatment with the concomitant medications ranged from 1 day to 5 days. Except for 1 participant who was treated during the in-clinic period (Days -1 to 4), all other concomitant medications were recorded during the ambulatory period (Days 6 to 113).
Change From Baseline in Vital Signs by Timepoint: Pulse Rate	Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
Change From Baseline in Vital Signs by Timepoint: Respiratory Rate	Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
Change From Baseline in Vital Signs by Timepoint: Systolic Blood Pressure	Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
Change From Baseline in Vital Signs by Timepoint: Temperature (Axillary)	Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
Change From Baseline in Electrocardiogram (ECG) Results by Timepoint: Heart Rate	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
Change From Baseline in ECG Results by Timepoint: PR Duration	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
Change From Baseline in ECG Results by Timepoint: QRS Duration	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
Change From Baseline in ECG Results by Timepoint: QT Duration	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
AUC Between Time Zero and the Time of Last Quantifiable Concentration (AUC0-last) of Emicizumab	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.
Time to Cmax (Tmax) of Emicizumab	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.
Apparent Clearance (CL/F) of Emicizumab	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.
Apparent Volume of Distribution (Vz/F) of Emicizumab	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADA) Against Emicizumab by Timepoint and for the Overall Study	Predose at Baseline (Day 1) and postdose on Days 57 and 113	Participants were considered to be 'ADA Negative (Treatment Unaffected)' if baseline and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that was at least 4-fold greater than the titer of the baseline sample. 'Total ADA Positive' is the sum of all participants who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Induced)', those who were ADA negative at baseline and tested positive for ADA following study drug administration; and 'ADA Positive (Treatment Boosted)', those who were pre-dose ADA positive and had post-baseline samples with a titer that was at least 4-fold greater compared to the baseline measurement.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: C-Reactive Protein Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in ECG Results by Timepoint: QTcF Duration (Fridericia's Correction Formula)	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
Change From Baseline in ECG Results by Timepoint: RR Duration	Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113	The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug.
Apparent Terminal Half-Life (t1/2) of Emicizumab	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.
Mean Residence Time (MRT) of Emicizumab	Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113	Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Bilirubin Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Fasting Blood Glucose Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Blood Urea Nitrogen Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Cholesterol Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Prothrombin Time	Baseline and Days 2, 11, 29, 57 and 113	Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils, Absolute Count	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Number of Participants With Laboratory Test Abnormalities	Baseline and Days 2, 4, 8, 11, 15, 29, 43, 57, 71, 85, and 113	The number of participants with a laboratory abnormality during treatment (numerator) is reported among the 'number analyzed' in the table below (denominator), which represents the number of participants without that abnormality at baseline (last observation prior to initiation of study drug). Note that samples from all participants were analyzed for each laboratory parameter. Values falling above or below the Roche predefined standard reference range were laboratory abnormalities labelled accordingly as 'high' or 'low'. Not every laboratory abnormality qualified as an adverse event; only if it was accompanied by clinical symptoms, resulted in a change in study treatment or in a medical intervention, or was clinically significant in the investigator's judgment. SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate transaminase; SGPT/ALT = serum glutamic-pyruvic transaminase/alanine transaminase
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Albumin Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Creatine Kinase Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Potassium Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Fasting Triglycerides Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Uric Acid Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Chloride Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Gamma Glutamyl Transferase Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Total Protein Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: SGOT/AST Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate transaminase
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: SGPT/ALT Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. SGPT/ALT = serum glutamic-pyruvic transaminase/alanine transaminase
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils, Absolute Count	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes, Absolute Count	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Creatinine Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Lactate Dehydrogenase Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Sodium Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Prothrombin Time/International Normalized Ratio (INR)	Baseline and Days 2, 11, 29, 57 and 113	The INR is a standardized measure of the prothrombin time. Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Number of Participants by Test Results for Glucose in Urine by Timepoint	Baseline and Days 2, 8, 29, 57, 85, and 113	Urine samples were collected from participants at the indicated timepoints for evaluation of urinalysis parameters. The number of participants with test results for glucose in urine of 0 (Absent), +1 (Trace), +2 (Positive), and +3/+4 (Strong Positive) at baseline and each timepoint are reported. Baseline was defined as the participant's last sample prior to initiation of study drug.
Number of Participants by Test Results for Protein in Urine by Timepoint	Baseline and Days 2, 8, 29, 57, 85, and 113	Urine samples were collected from participants at the indicated timepoints for evaluation of urinalysis parameters. The number of participants with test results for protein in urine of 0 (Absent), +1 (Trace), +2 (Positive), and +3/+4 (Strong Positive) at baseline and each timepoint are reported. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Direct Bilirubin Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Volume	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	Erythrocyte mean corpuscular volume is a measure of the average volume of a 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit (as a Fraction of 1)	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Number of Participants With Adverse Events by Highest World Health Organization (WHO) Toxicity Grade	From screening to study completion (20 weeks)	The WHO Toxicity Grading Scale was used for assessing adverse event severity. Any adverse event not specifically listed in the WHO Toxicity Grading Scale was assessed according to the following levels of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe; and Grade 4 is life-threatening. Investigator text for adverse events were encoded using the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. After informed consent had been obtained but prior to initiation of study drug, only serious adverse events (SAEs) caused by a protocol-mandated intervention were to have been reported. After initiation of study drug, all adverse events, regardless of relationship to study drug, were to have been reported until the participant completed his last study visit. After this period, any SAEs believed to be related to prior study drug treatment were to be reported.
Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Activated Partial Thromboplastin Time	Baseline and Days 2, 11, 29, 57, and 113	Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Fibrinogen Concentration	Baseline and Days 2, 11, 29, 57 and 113	Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Hemoglobin	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	Erythrocyte mean corpuscular hemoglobin (MCH) is a measure of the average amount 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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Hemoglobin Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin Concentration	Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113	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. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug.