Non-alcoholic SteatohepatitisPhase 1NCT05668936
A Thorough QTC Study to Assess the Effect of Cotadutide on Cardiac Repolarization in Healthy Participants
A Phase 1 study testing Cotadutide and Moxifloxacin in people with Non-alcoholic Steatohepatitis, run by AstraZeneca at 1 site in Germany.
Trial summary
This study will investigate the effect of multiple doses of cotadutide on the cardiac activity (QTc interval) of healthy participants. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Steatohepatitis
- What is being tested?
- Cotadutide and Moxifloxacin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteGermany
- Study dates
- 3 Jan 2023to 10 Mar 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male and female participants of age 18 to 55 years.
- Females must have a negative pregnancy test.
- Have a Body Mass Index (BMI) of ≥ 18 and ≤ 29.9 kg/m^2.
Who cannot join
- History or presence of any clinically significant disease or disorder.
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition (including gastrointestinal surgery) known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- History of acute or chronic pancreatitis.
- Family history of sudden cardiac death before the age of 50 of a first-degree relative.
- History of additional risk factors for Torsade de Pointes (eg, heart failure, clinically important bradycardia and electrolyte disturbances eg, hypokalemia, hypocalcemia, hypomagnesemia or family history of long QT syndrome).
- History of neoplastic disease
Show all 14Show fewer
- Any clinically significant abnormalities in clinical chemistry, hematology, urinalysis results or vital signs.
- Any clinically significant abnormalities in rhythm, conduction, or morphology of the 12-lead resting electrocardiogram (ECG).
- Any positive result on screening for serum hepatitis B surface antigen OR anti-HBc antibody, indicative of active hepatitis B (ie, participants with positive anti-HBc antibody result are acceptable if anti HBc IgM antibodies are negative), hepatitis C antibody, and Human immunodeficiency virus (HIV) antibody.
- Current smokers or those who have smoked or used nicotine products (including e-cigarettes).
- Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
- Use of drugs with enzyme-inducing properties such as St John's Wort.
- Participant has a positive test result for SARS-CoV-2 RT-PCR during screening period or at baseline.
- Participant has clinical signs and symptoms consistent with COVID-19 or a history of severe COVID-19 (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Thorough QTc Evaluation of the Effect of Cotadutide on Cardiac Repolarization in Healthy Participants: A Randomized, Double-blind, Placebo-controlled, 3-arm Parallel Study With a Nested Crossover Design for Positive Control With Moxifloxacin Administration
This study will investigate the effect of multiple doses of cotadutide on the cardiac activity (QTc interval) of healthy participants.
Read the detailed description
This study will be a randomized, double-blind, placebo-controlled 3-arm parallel study with a nested crossover design for positive control with moxifloxacin administration in healthy male and female participants.
Participants will be randomized to receive treatment with either cotadutide during the 13-week treatment period (Arm 1) or cotadutide-placebo (Arm 2).
The cotadutide-placebo treatment arm will be further divided into 2 subgroups (Arms 2A and 2B), in a nested crossover design for only the placebo-treated participants.
Participants will be randomized in a 2:1:1 ratio to Arm 1, Arm 2A, and Arm 2B.
Approximately 80 participants will be randomized to have 64 evaluable participants in the study.
Each participant will be involved in the study for approximately 22 weeks.
- Conditions
- Non-alcoholic Steatohepatitis
- Being tested
- Cotadutide, Cotadutide-placebo, Moxifloxacin, Moxifloxacin-placebo
- Keywords
- Non-alcoholic fatty liver disease, Glucagon-like peptide-1 (GLP-1) receptor
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CotadutideDrug
Participants will receive a subcutaneous injection of cotadutide.
Cotadutide-placeboDrug
Participants will receive a subcutaneous injection of cotadutide-placebo.
MoxifloxacinDrug
Participants will receive a single oral dose of Moxifloxacin film-coated tablet.
Moxifloxacin-placeboDrug
Participants will receive a single oral dose of Moxifloxacin-placebo film-coated tablet.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Participants will receive cotadutide and will receive a single dose of moxifloxacin-placebo on Day 1 and Day 93. Receives: Drug: Cotadutide; Drug: Moxifloxacin-placebo |
| Arm 2A | Experimental | Participants will receive a single dose of moxifloxacin (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin-placebo on Day 93. Receives: Drug: Cotadutide-placebo; Drug: Moxifloxacin; Drug: Moxifloxacin-placebo |
| Arm 2B | Experimental | Participants will receive a single dose of moxifloxacin-placebo (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin on Day 93. Receives: Drug: Cotadutide-placebo; Drug: Moxifloxacin; Drug: Moxifloxacin-placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time-matched change-from-baseline Fridericia's correction of QT interval (QTcF)
Time-matched change-from-baseline QTcF after cotadutide administration compared with placebo will be assesed using a C-QTc interval analysis. The method that removes the HR dependence of the QT interval most efficiently will be chosen as the primary correction method and its corresponding change from baseline QTc will be the primary endpoint.
Measured: Up to Day 92
Secondary outcomes (25)
Change from baseline in QTcF
Change from baseline in QTcF after moxifloxacin administration compared with placebo will be assessed.
Measured: Up to Day 94
Change from baseline in Heart rate (HR)
The effect of cotadutide on HR will be assessed.
Measured: From Day 2 up to Day 92 or early discontinuation
Change from baseline in PR interval
The effect of cotadutide on PR interval will be assessed.
Measured: From Day 2 up to Day 92 or early discontinuation
Change from baseline in QRS interval
The effect of cotadutide on QRS will be assessed.
Measured: From Day 2 up to Day 92 or early discontinuation
Number of participants with significant change in QTcF
The presence of categorical outliers for QTc after cotadutide administration will be assessed.
Measured: From Day 2 up to Day 92 or early discontinuation
Number of participants with significant change in HR
The presence of categorical outliers for HR after cotadutide administration will be assessed.
Measured: From Day 2 up to Day 92 or early discontinuation
Number of participants with significant change in PR interval
The presence of categorical outliers for PR after cotadutide administration will be assessed.
Measured: From Day 2 up to Day 92 or early discontinuation
Number of participants with significant change in QRS interval
The presence of categorical outliers for QRS after cotadutide administration will be assessed.
Measured: From Day 2 up to Day 92 or early discontinuation
Number of treatment-emergent changes in T-wave morphology
Morphological changes in the T-U complex after cotadutide administration will be investigated.
Measured: From Day 2 up to Day 92 or early discontinuation
Number of treatment-emergent changes in U-waves presence
Morphological changes in the T-U complex after cotadutide administration will be investigated.
Measured: From Day 2 up to Day 92 or early discontinuation
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) of cotadutide
AUClast as a variable of the pharmacokinetics (PK) of cotadutide will be assessed.
Measured: Day 57 and Day 91
Area under concentration-time curve in the dose interval (AUCtau) of cotadutide
AUCtau as a variable of the PK of cotadutide will be assessed.
Measured: Day 57 and Day 91
Maximum observed plasma concentration (Cmax) of cotadutide
Cmax as a variable of the PK of cotadutide will be assessed.
Measured: Day 57 and Day 91
Time to reach maximum observed plasma concentration (tmax) of cotadutide
tmax as a variable of the PK of cotadutide will be assessed.
Measured: Day 57 and Day 91
Change from baseline in mean systolic blood pressure (SBP)
The effect of cotadutide on blood pressure (BP) by Ambulatory blood pressure monitoring (ABPM) will be investigated.
Measured: Up to Day 92
Change from baseline in mean diastolic blood pressure (DBP)
The effect of cotadutide on BP by ABPM will be investigated.
Measured: Up to Day 92
Change from baseline in mean HR
The effect of cotadutide on HR by ABPM will be investigated.
Measured: Up to Day 92
Placebo-corrected mean change from baseline in SBP
The effect of cotadutide on BP by ABPM will be investigated.
Measured: Up to Day 92
Placebo-corrected mean change from baseline in DBP
The effect of cotadutide on BP by ABPM will be investigated.
Measured: Up to Day 92
Placebo-corrected mean change from baseline in HR
The effect of cotadutide on HR by ABPM will be investigated.
Measured: Up to Day 92
Number of participants with significant change in SBP
The effect of cotadutide on BP by ABPM will be investigated.
Measured: Up to Day 92
Number of participants with change in DBP
The effect of cotadutide on BP by ABPM will be investigated.
Measured: Up to Day 92
Number of participants with significant change in HR
The effect of cotadutide on HR by ABPM will be investigated.
Measured: Up to Day 92
Number of participants with Adverse Events (AEs)
The safety and tolerability of cotadutide will be assessed.
Measured: Up to follow-up visit 28 days post last dose (approximately Day 120)
Number of participants with Antidrug Antibodies to cotadutide
The immunogenicity of cotadutide will be evaluated.
Measured: Day 2, 30, 57, 91 and Day 120 (follow-up visit 28 days post last dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2022
- Study start3 Jan 2023
- Primary completion10 Mar 2023
- Study completion10 Mar 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 Non-alcoholic SteatohepatitisStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05668936
- Sponsor's protocol ID
- D5671C00010
- Other IDs
- 2022-002479-12
- Status last verified
- Mar 2023
- First submitted
- 20 Dec 2022
- Last updated
- 5 Apr 2023
- Results posted
- No
- FDA-regulated drug
- No
- 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 requests 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 5 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Thorough QTc Evaluation of the Effect of Cotadutide on Cardiac Repolarization in Healthy Participants: A Randomized, Double-blind, Placebo-controlled, 3-arm Parallel Study With a Nested Crossover Design for Positive Control With Moxifloxacin Administration
- ClinicalTrials.gov ID
- NCT05668936
- Acronym / sponsor ID
- D5671C00010
- Conditions
- Non-alcoholic Steatohepatitis
- Keywords
- Non-alcoholic fatty liver disease, Glucagon-like peptide-1 (GLP-1) receptor
- 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
- 31 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 3 Jan 2023 (actual)
- Primary completion
- 10 Mar 2023 (actual)
- Study completion
- 10 Mar 2023 (actual)
- First posted
- 30 Dec 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 investigate the effect of multiple doses of cotadutide on the cardiac activity (QTc interval) of healthy participants.
Detailed description
This study will be a randomized, double-blind, placebo-controlled 3-arm parallel study with a nested crossover design for positive control with moxifloxacin administration in healthy male and female participants.
Participants will be randomized to receive treatment with either cotadutide during the 13-week treatment period (Arm 1) or cotadutide-placebo (Arm 2).
The cotadutide-placebo treatment arm will be further divided into 2 subgroups (Arms 2A and 2B), in a nested crossover design for only the placebo-treated participants.
Participants will be randomized in a 2:1:1 ratio to Arm 1, Arm 2A, and Arm 2B.
Approximately 80 participants will be randomized to have 64 evaluable participants in the study.
Each participant will be involved in the study for approximately 22 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Cotadutide, Drug: Moxifloxacin-placeboParticipants will receive cotadutide and will receive a single dose of moxifloxacin-placebo on Day 1 and Day 93. |
| Arm 2A | Experimental | Drug: Cotadutide-placebo, Drug: Moxifloxacin, Drug: Moxifloxacin-placeboParticipants will receive a single dose of moxifloxacin (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin-placebo on Day 93. |
| Arm 2B | Experimental | Drug: Cotadutide-placebo, Drug: Moxifloxacin, Drug: Moxifloxacin-placeboParticipants will receive a single dose of moxifloxacin-placebo (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin on Day 93. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy male and female participants of age 18 to 55 years.
- Females must have a negative pregnancy test.
- Have a Body Mass Index (BMI) of ≥ 18 and ≤ 29.9 kg/m^2.
Key exclusion criteria (14 listed)
- History or presence of any clinically significant disease or disorder.
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition (including gastrointestinal surgery) known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- History of acute or chronic pancreatitis.
- Family history of sudden cardiac death before the age of 50 of a first-degree relative.
- History of additional risk factors for Torsade de Pointes (eg, heart failure, clinically important bradycardia and electrolyte disturbances eg, hypokalemia, hypocalcemia, hypomagnesemia or family history of long QT syndrome).
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 a subcutaneous injection of cotadutide. | Drug | Arm 1 |
| Cotadutide-placeboParticipants will receive a subcutaneous injection of cotadutide-placebo. | Drug | Arm 2A, Arm 2B |
| MoxifloxacinParticipants will receive a single oral dose of Moxifloxacin film-coated tablet. | Drug | Arm 2A, Arm 2B |
| Moxifloxacin-placeboParticipants will receive a single oral dose of Moxifloxacin-placebo film-coated tablet. | Drug | Arm 1, Arm 2A, Arm 2B |
Primary outcome
Time-matched change-from-baseline Fridericia's correction of QT interval (QTcF)
Time frame: Up to Day 92
Time-matched change-from-baseline QTcF after cotadutide administration compared with placebo will be assesed using a C-QTc interval analysis. The method that removes the HR dependence of the QT interval most efficiently will be chosen as the primary correction method and its corresponding change from baseline QTc will be the primary endpoint.
25 secondary outcomes
Change from baseline in QTcF
Time frame: Up to Day 94
Change from baseline in Heart rate (HR)
Time frame: From Day 2 up to Day 92 or early discontinuation
Change from baseline in PR interval
Time frame: From Day 2 up to Day 92 or early discontinuation
Change from baseline in QRS interval
Time frame: From Day 2 up to Day 92 or early discontinuation
Number of participants with significant change in QTcF
Time frame: From Day 2 up to Day 92 or early discontinuation
Number of participants with significant change in HR
Time frame: From Day 2 up to Day 92 or early discontinuation
Number of participants with significant change in PR interval
Time frame: From Day 2 up to Day 92 or early discontinuation
Number of participants with significant change in QRS interval
Time frame: From Day 2 up to Day 92 or early discontinuation
Number of treatment-emergent changes in T-wave morphology
Time frame: From Day 2 up to Day 92 or early discontinuation
Number of treatment-emergent changes in U-waves presence
Time frame: From Day 2 up to Day 92 or early discontinuation
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) of cotadutide
Time frame: Day 57 and Day 91
Area under concentration-time curve in the dose interval (AUCtau) of cotadutide
Time frame: Day 57 and Day 91
Maximum observed plasma concentration (Cmax) of cotadutide
Time frame: Day 57 and Day 91
Time to reach maximum observed plasma concentration (tmax) of cotadutide
Time frame: Day 57 and Day 91
Change from baseline in mean systolic blood pressure (SBP)
Time frame: Up to Day 92
Change from baseline in mean diastolic blood pressure (DBP)
Time frame: Up to Day 92
Change from baseline in mean HR
Time frame: Up to Day 92
Placebo-corrected mean change from baseline in SBP
Time frame: Up to Day 92
Placebo-corrected mean change from baseline in DBP
Time frame: Up to Day 92
Placebo-corrected mean change from baseline in HR
Time frame: Up to Day 92
Number of participants with significant change in SBP
Time frame: Up to Day 92
Number of participants with change in DBP
Time frame: Up to Day 92
Number of participants with significant change in HR
Time frame: Up to Day 92
Number of participants with Adverse Events (AEs)
Time frame: Up to follow-up visit 28 days post last dose (approximately Day 120)
Number of participants with Antidrug Antibodies to cotadutide
Time frame: Day 2, 30, 57, 91 and Day 120 (follow-up visit 28 days post last dose)
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 5 Apr 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 requests 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.
1 site 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 and Moxifloxacin in people with Non-alcoholic Steatohepatitis, run by AstraZeneca at 1 site in Germany.
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 3 inclusion and 14 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 5 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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?
Time-matched change-from-baseline Fridericia's correction of QT interval (QTcF) (time frame: Up to Day 92). 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 5 Apr 2023.