Hepatic ImpairmentPhase 1NCT05517226
Pharmacokinetics of Cotadutide in Participants With Hepatic Impairment
A Phase 1 study testing Cotadutide in people with Hepatic Impairment, run by AstraZeneca at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- Cotadutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesUnited States
- Study dates
- 6 Sep 2022to 27 Feb 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
- Participants with hepatic impairment only
- Severe portal hypertension or surgical porto-systemic shunts.
- Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
- Clinically relevant hepatic encephalopathy.
- Severe ascites defined as ascites requiring paracentesis and albumin at 4-week intervals or less.
- Fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment within the 28-day Screening period.
- Post liver transplantation.
- Platelet count < 50 × 109/L and/or neutrophil count < 1.2 × 109/L and/or hemoglobin < 8.5 g/dL or INR >2.3.
- Participants with normal hepatic function only
- History or presence of hepatic disease or evidence of other known forms of known chronic liver disease.
- History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Urinary albumin-to-creatinine ratio > 3 mg/μmol.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Research Site
Hialeah, Florida, 33014
Research Site
San Antonio, Texas, 78215
Research Site
San Antonio, Texas, 78229
About this study
Official title: 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
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.
Read the 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
- Conditions
- Hepatic Impairment
- Being tested
- Cotadutide
- Keywords
- Cotadutide, Hepatic impairment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CotadutideCombination product
Participants will receive cotadutide subcutaneously.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Participants in each cohort will receive Dose A cotadutide subcutaneously. Receives: Combination Product: Cotadutide |
| Cohort 2 | Experimental | Participants in each cohort will receive Dose A cotadutide subcutaneously. Receives: Combination Product: Cotadutide |
| Cohort 3 | Experimental | Participants in each cohort will receive Dose A cotadutide subcutaneously. Receives: Combination Product: Cotadutide |
| Cohort 4 | Experimental | Participants in each cohort will receive Dose A cotadutide subcutaneously. Receives: Combination Product: Cotadutide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 to Day 3
Secondary outcomes (2)
Number of participants with Adverse Events (AEs)
The safety, and tolerability of a single dose of cotadutide in participants with hepatic impairment will be assessed.
Measured: From time of first dose to the final follow-up visit (Day 29)
Incidence of ADAs (anti-drug antibodies)
The safety, and tolerability of a single dose of cotadutide in participants with hepatic impairment will be assessed.
Measured: From time of first dose to the final follow-up visit (Day 29)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2022
- Study start6 Sep 2022
- Primary completion27 Feb 2023
- Study completion27 Feb 2023
Why it stopped: Discontinuing the development of cotadutide, a daily injectable GLP-1/glucagon co-agonist, is based on strategic pipeline considerations. The premature closure is not due to any newly observed safety signals or a change in the risk/benefit profile.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05517226
- Sponsor's protocol ID
- D5671C00008
- Status last verified
- Mar 2023
- First submitted
- 24 Aug 2022
- Last updated
- 21 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05517226
- Acronym / sponsor ID
- D5671C00008
- Conditions
- Hepatic Impairment
- Keywords
- Cotadutide, Hepatic impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Discontinuing the development of cotadutide, a daily injectable GLP-1/glucagon co-agonist, is based on strategic pipeline considerations. The premature closure is not due to any newly observed safety signals or a change in the risk/benefit profile.
- Enrolment
- 24 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 6 Sep 2022 (actual)
- Primary completion
- 27 Feb 2023 (actual)
- Study completion
- 27 Feb 2023 (actual)
- First posted
- 26 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Combination Product: CotadutideParticipants in each cohort will receive Dose A cotadutide subcutaneously. |
| Cohort 2 | Experimental | Combination Product: CotadutideParticipants in each cohort will receive Dose A cotadutide subcutaneously. |
| Cohort 3 | Experimental | Combination Product: CotadutideParticipants in each cohort will receive Dose A cotadutide subcutaneously. |
| Cohort 4 | Experimental | Combination Product: CotadutideParticipants in each cohort will receive Dose A cotadutide subcutaneously. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (27 listed)
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CotadutideParticipants will receive cotadutide subcutaneously. | Combination product | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
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.
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.
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.
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.
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.
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.
2 secondary outcomes
Number of participants with Adverse Events (AEs)
Time frame: From time of first dose to the final follow-up visit (Day 29)
Incidence of ADAs (anti-drug antibodies)
Time frame: From time of first dose to the final follow-up visit (Day 29)
Results and safety
The study was stopped early (reason given: Discontinuing the development of cotadutide, a daily injectable GLP-1/glucagon co-agonist, is based on strategic pipeline considerations. The premature closure is not due to any newly observed safety signals or a change in the risk/benefit profile.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2023.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cotadutide in people with Hepatic Impairment, run by AstraZeneca at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Discontinuing the development of cotadutide, a daily injectable GLP-1/glucagon co-agonist, is based on strategic pipeline considerations. The premature closure is not due to any newly observed safety signals or a change in the risk/benefit profile.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum observed plasma (peak) drug concentration [Cmax] (time frame: Day 1 to Day 3). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2023.