Pharmacokinetics of Cotadutide in Participants With Hepatic Impairment

NCT05517226 | Terminated Phase 1 FDA Drug

• 1 other identifier: D5671C00008
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

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.

Conditions

Hepatic Impairment

Keywords

Cotadutide; Hepatic impairment

Outcome Measures

Primary Outcomes (7)

• Maximum observed plasma (peak) drug concentration [Cmax]

  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.

  Day 1 to Day 3

• Area under plasma concentration time curve from zero to infinity (AUCinf)

  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.

  Day 1 to Day 3

• Area under the plasma concentration-curve from time zero to last quantifiable concentration (AUClast)

  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.

  Day 1 to Day 3

• Time to reach peak or maximum observed concentration or response following drug administration (tmax)

  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.

  Day 1 to Day 3

• Terminal half-life (t½λz)

  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.

  Day 1 to Day 3

• Apparent total body clearance (CL/F)

  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.

  Day 1 to Day 3

• Apparent volume of distribution based on the terminal phase (Vz/F)

  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.

  Day 1 to Day 3

Secondary Outcomes (2)

• Number of participants with Adverse Events (AEs)

  From time of first dose to the final follow-up visit (Day 29)

• Incidence of ADAs (anti-drug antibodies)

  From time of first dose to the final follow-up visit (Day 29)

Study Arms (4)

Cohort 1

EXPERIMENTAL

Participants in each cohort will receive Dose A cotadutide subcutaneously.

Combination Product: Cotadutide

Cohort 2

EXPERIMENTAL

Participants in each cohort will receive Dose A cotadutide subcutaneously.

Combination Product: Cotadutide

Cohort 3

EXPERIMENTAL

Participants in each cohort will receive Dose A cotadutide subcutaneously.

Combination Product: Cotadutide

Cohort 4

EXPERIMENTAL

Participants in each cohort will receive Dose A cotadutide subcutaneously.

Combination Product: Cotadutide

Interventions

Cotadutide COMBINATION_PRODUCT

Participants will receive cotadutide subcutaneously.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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/m2.
• 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).

You may not qualify if:

• 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).
• Any sign and confirmation of coronavirus disease 2019 (COVID19) infection:
• Participants with concurrent or previous use of a glucagon-like peptide-1 (GLP1) receptor agonist.
• Use of prohibited prescribed or nonprescribed medication during the 2 weeks prior to the first administration of Investigational Medicinal Product (IMP) or longer if the medication has a long half-life.
• History of neoplastic disease within 5 years prior to Screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer.
• Presence of hepatocellular carcinoma or acute liver disease caused by an infection or drug toxicity.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (3)

Research Site

Hialeah, Florida, 33014, United States

Location

Research Site

San Antonio, Texas, 78215, United States

Location

Research Site

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Interventions

cotadutide

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2022
• First Posted: August 26, 2022
• Study Start: September 6, 2022
• Primary Completion: February 27, 2023
• Study Completion: February 27, 2023
• Last Updated: March 21, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (3)