A First-in-Human Study to Assess the Safety, Tolerability and Pharmacokinetics of anle138b in Healthy Male and Female Subjects
Overview
- Phase
- Phase 1
- Intervention
- anle138b
- Conditions
- Healthy Volunteers
- Sponsor
- MODAG GmbH
- Enrollment
- 68
- Locations
- 1
- Primary Endpoint
- Incidence of treatment-emergent adverse events in healthy volunteers with single ascending doses of anle138b (Part 1)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to determine the safety, tolerability and blood levels of orally administered anle138b in healthy subjects.
Detailed Description
This is a single-centre, study of double-blind, randomised, placebo-controlled single ascending doses (SAD) and multiple ascending doses (MAD) of anle138b in healthy subjects in study Parts 1 and 2. In study Part 3 the effect of food (FES) on the safety and PK of anle138b in healthy subjects is examined. In the SAD cohorts, subjects will be randomly assigned to receive a single oral dose of active investigational medicinal product (IMP) or matching placebo in a sequential escalating manner with sufficient time planned between dose groups to allow interim review of the data. In the MAD cohorts, subjects will be randomly assigned to receive oral doses of active IMP or matching placebo once daily (QD) for 7 days, in a sequential escalating manner with sufficient time planned between dose groups to allow interim review of the data. In the FES, the effect of food on the safety and PK of anle138b is explored by administering a single dose of IMP after a high-fat breakfast. Subjects will be randomly assigned to one of 2 treatment sequence to receive anle138b in the fed or fasted state over 2 periods.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy males or women of no child bearing potential
- •Age 18 to 55 years of age at the time of signing informed consent
- •Body mass index (BMI) of 18.5 to 30.0 kg/m2 as measured at screening
- •Must be willing and able to communicate and participate in the whole study
- •Must provide written informed consent
- •Must agree to adhere to the contraception requirements defined in Section 9.4
- •In the investigator's opinion, subject is able to understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the protocol restrictions and requirements.
Exclusion Criteria
- •Subjects who have received any IMP in a clinical research study within the 90 days prior to Day
- •Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
- •Subjects who have previously been enrolled in this study. Subjects who have taken part in Part 1 are not permitted to take part in Part 2 or Part 3; subjects who have taken part in Part 2 are not permitted to take part in Part
- •History of any drug or alcohol abuse in the past 2 years.
- •Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type).
- •A confirmed positive alcohol breath test at screening or admission.
- •Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission.
- •Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months.
- •Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative urine pregnancy test at screening and serum pregnancy test on admission). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle stimulating hormone concentration ≥40 IU/L).
- •Subjects with pregnant or lactating partners.
Arms & Interventions
anle138b
Dosage: 50 mg and higher Dosage form: capsule Frequency: once daily Duration: One day for SAD and seven days for MAD
Intervention: anle138b
placebo
Matching placebo Dosage form: capsule Frequency: once daily Duration: One day for SAD and seven days for MAD
Intervention: Placebo
Outcomes
Primary Outcomes
Incidence of treatment-emergent adverse events in healthy volunteers with single ascending doses of anle138b (Part 1)
Time Frame: Day 1 to day 30 post dose
Adverse events (AEs)
Incidence of treatment-emergent changes in clinical laboratory parameters in healthy volunteers with single ascending doses of anle138b (Part 1)
Time Frame: Day 1 to day 7 post dose
clinical laboratory tests including hematology and clinical chemistry including renal function tests, hepatic enzymes, electrolytes and creatine kinase
Incidence of treatment-emergent changes in vital signs in healthy volunteers with single ascending doses of anle138b (Part 1)
Time Frame: Day 1 to day 7 post dose
Blood pressure, heart rate, oral temperature
Incidence of treatment-emergent ECG changes in healthy volunteers with single ascending doses of anle138b (Part 1)
Time Frame: Day 1 to day 7 post dose
Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)
Incidence of treatment-emergent changes in physical examination in healthy volunteers with single ascending doses of anle138b (Part 1)
Time Frame: Day 1 to day 7 post dose
physical examination findings
Incidence of treatment-emergent adverse events in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Time Frame: Day 1 to day 30 post dose
Adverse events (AEs)
Incidence of treatment-emergent changes in clinical laboratory parameters in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Time Frame: Day 1 to day 7 post dose
clinical laboratory tests including hematology and clinical chemistry including renal function tests, hepatic enzymes, electrolytes and creatine kinase
Incidence of treatment-emergent changes in vital signs in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Time Frame: Day 1 to day 7 post dose
Blood pressure, heart rate, oral temperature
Incidence of treatment-emergent ECG changes in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Time Frame: Day 1 to day 7 post dose
Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)
Incidence of treatment-emergent changes in physical examination in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Time Frame: Day 1 to day 7 post dose
physical examination findings
Incidence of treatment-emergent adverse events in healthy volunteers with a single dose of anle138b both the fasted and fed state (Part 3)
Time Frame: Day 1 to day 30 post dose.
Adverse events (AEs)
Incidence of treatment-emergent changes in clinical laboratory parameters in healthy volunteers with a single dose of anle138b both in the fasted and in the fed state (Part 3)
Time Frame: Day 1 to day 7 post dose
clinical laboratory tests including hematology and clinical chemistry including renal function tests, hepatic enzymes, electrolytes and creatine kinase
Incidence of treatment-emergent changes in vital signs in healthy volunteers with a single dose of anle138b both in the fasted and in the fed state (Part 3)
Time Frame: Day 1 to day 7 post dose
Blood pressure, heart rate, oral temperature
Incidence of treatment-emergent ECG changes in healthy volunteers with a single dose of anle138b both in the fasted and in the fed state (Part 3)
Time Frame: Day 1 to day 7 post dose
Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)
Incidence of treatment-emergent changes in physical examination in healthy volunteers with single ascending doses of anle138b both in the fasted and in the fed state (Part 3)
Time Frame: Day 1 to day 7 post dose
physical examination findings
Secondary Outcomes
- Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state(From dosing to 48 hours post dosing)
- Oral pharmacokinetics (PK) of single (Part 1) and multiple (Part 2) ascending doses of anle138b in the fasted state(Day 1 to day 9)
- Oral pharmacokinetics (PK) (Part 3) for anle138b in the fed and fasted states.(From dosing to 48 hours post dosing)
- Oral pharmacokinetics (PK) of multiple (Part 2) ascending doses of anle138b in the fasted state(Day 1 to day 9)
- Oral pharmacokinetics (PK) (Part 3) for anle138b in the fed and fasted states(From dosing to 48 hours post dosing)