A Phase I, Parallel-group, Multi-center, Open-label, Investigation of the Pharmacokinetics, Safety and Tolerability of a Single Subcutaneous Injection of Cotadutide in Participants With Mild, Moderate or Severe Hepatic Impairment Compared to Participants With Normal Hepatic Function
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Hepatic Impairment
- Sponsor
- AstraZeneca
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Apparent total body clearance (CL/F)
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
This study will assess the pharmacokinetics (PK), safety, and tolerability of a single subcutaneous injection of cotadutide in participants with mild, moderate or severe hepatic impairment compared to participants with normal hepatic function.
Detailed Description
This study will consist of four cohorts (Cohort 1, Cohort 2, Cohort 3, and Cohort 4). Participants will be assigned to each of the cohorts as per Child-Pugh classification: * Cohort 1: Mild hepatic impairment (Child-Pugh A), cotadutide 50 μg * Cohort 2: Moderate hepatic impairment (Child-Pugh B), cotadutide 50 μg * Cohort 3: Severe hepatic impairment (Child-Pugh C), cotadutide 50 μg * Cohort 4: Normal hepatic function, cotadutide 50 μg
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant must be ≥ 18 to ≤ 85 years of age at the time of signing the Informed Consent Form (ICF).
- •Body mass index ≥ 18 kg/m2 to \< 40 kg/m
- •Female participants of childbearing potential must use at least one highly effective form of birth control.
- •Capable of giving signed informed consent.
- •Participants with hepatic impairment only
- •Diagnosis of chronic (≥ 6 months) and stable hepatic impairment (eg, no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status within 30 days prior to study Screening).
Exclusion Criteria
- •All participants
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to cotadutide.
- •Any clinically important abnormalities in rhythm, conduction or morphology of the 12-lead resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG as considered by the Investigator that may interfere with the interpretation of QT interval corrected for heart rate using Fridericia's formula (QTcF), including abnormal ST-T-wave morphology, or left ventricular hypertrophy
- •Prolonged QTcF \> 470 ms or family history of long QT syndrome.
- •PR (PQ) interval shortening \< 120 ms.
- •PR (PQ) interval prolongation (\> 220 ms) intermittent or permanent second or third degree atrioventricular (AV) block, or AV dissociation.
- •Persistent or intermittent complete bundle branch block, or intraventricular conduction delay with QRS \> 119 ms.
- •Any evidence of additional severe or uncontrolled systemic disease or laboratory finding that makes it unsafe for the participant to participate in the study.
- •Impaired renal function, defined as estimated glomerular filtration rate (eGFR) \< 30 mL/minute/1.73 m2 at Screening.
- •Any positive result on Screening for serum hepatitis B surface antigen, anti-Core HBV antibody, hepatitis C antibody, or human immunodeficiency virus (HIV).
Outcomes
Primary Outcomes
Apparent total body clearance (CL/F)
Time Frame: Day 1 to Day 3
The CL/F of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed.
Area under plasma concentration time curve from zero to infinity (AUCinf)
Time Frame: Day 1 to Day 3
The AUCinf of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed.
Area under the plasma concentration-curve from time zero to last quantifiable concentration (AUClast)
Time Frame: Day 1 to Day 3
The AUClast of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed.
Terminal half-life (t½λz)
Time Frame: Day 1 to Day 3
The t½λz of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed.
Maximum observed plasma (peak) drug concentration [Cmax]
Time Frame: Day 1 to Day 3
The Cmax of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed.
Time to reach peak or maximum observed concentration or response following drug administration (tmax)
Time Frame: Day 1 to Day 3
The tmax of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed.
Apparent volume of distribution based on the terminal phase (Vz/F)
Time Frame: Day 1 to Day 3
The Vz/F of a single dose of cotadutide in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function will be assessed.
Secondary Outcomes
- Incidence of ADAs (anti-drug antibodies)(From time of first dose to the final follow-up visit (Day 29))
- Number of participants with Adverse Events (AEs)(From time of first dose to the final follow-up visit (Day 29))