Safety and Tolerability Study of Cotadutide in Japanese Obese Subjects With Type 2 Diabetes Melitus

NCT04208620 | Completed Phase 1

• 1 other identifier: D5671C00003
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1 study designed to assess the safety and tolerability of MEDI0382 (Cotadutide) in Japanese T2DM patients.

Conditions

Type 2 Diabetes

Keywords

Diabetes; Cotadutide; MEDI0382; D5671C00003; Type 2 Diabetes

Outcome Measures

Primary Outcomes (8)

• Incidence of treatment-emergent adverse events (TEAEs)

  To assess the safety and tolerability of Cotadutide

  Baseline until the follow-up period, 28 days post-last dose

• Incidence of treatment-emergent serious adverse events (TESAEs)

  To assess the safety and tolerability of Cotadutide

  Baseline until the follow-up period, 28 days post-last dose

• Clinically important changes in 12-lead electrocardiogram (ECG)

  To assess the safety and tolerability of Cotadutide

  Baseline until the follow-up period, 28 days post-last dose

• Vital signs as measured by pulse rate (bpm)

  To assess the safety and tolerability of Cotadutide

  Baseline until the follow-up period, 28 days post-last dose

• Vital signs as measured by blood pressure (mmHg)

  To assess the safety and tolerability of Cotadutide

  Baseline until the follow-up period, 28 days post-last dose

• ABPM (Ambulatory blood pressure monitoring) to measure pulse rate (bpm) and blood pressure (mmHg)

  To assess the safety and tolerability of Cotadutide

  Baseline until the follow-up period, 28 days post-last dose

• Physical examination (abnormality to be reported as part of adverse events)

  To assess the safety and tolerability of Cotadutide

  Baseline until the follow-up period, 28 days post-last dose

• Clinical laboratory evaluations

  To assess the safety and tolerability of Cotadutide

  Baseline until the follow-up period, 28 days post-last dose

Secondary Outcomes (16)

• Area under the concentration-time curve (AUC) during the dosing interval (AUCtau)

  Day1 of Up-titration treatment period to Day 21 of Treatment extension period, total of up to 10 weeks

• Maximum observed concentration (Cmax)

  Day1 of Up-titration treatment period to Day 21 of Treatment extension period, total of up to 10 weeks

• Time to Cmax (tmax)

  Day1 of Up-titration treatment period to Day 21 of Treatment extension period, total of up to 10 weeks

• Trough plasma concentration (Ctrough)

  Day1 of Up-titration treatment period to Day 21 of Treatment extension period, total of up to 10 weeks

• Anti-drug antibodies (ADAs) to Cotadutide

  At baseline through end of study, 98 days in total

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo administered subcutaneously

Drug: Placebo

Cotadutide

EXPERIMENTAL

Cotadutide administered subcutaneously

Drug: Cotadutide

Interventions

Placebo DRUG

Placebo administered subcutaneously

Placebo

Cotadutide DRUG

Cotadutide administered subcutaneously

Cotadutide

Eligibility Criteria

• Age: 20 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated written informed consent prior to any mandatory study specific procedures, sampling, and analyses.
• Subject must be 20 to 74 years of age at screening.
• HbA1c range of 6.5% to 8.5% at screening and run-in visit.
• Willing and able to self-inject investigational product for the duration of the study.
• Individuals who are diagnosed with T2DM and have inadequate glycaemic control with diet and exercise.
• Individuals whose current condition at enrolment are drug naïve defined as
• Never received medical treatment for diabetes (insulin and/or other anti-diabetic agents \[oral or injection\]) OR
• Received medical treatment for diabetes for less than 30 days since diagnosis.Subjects also should not have a history of insulin therapy within 2 weeks of screening (with the exception of insulin therapy during a hospitalization for other causes or use in gestational diabetes) OR
• Previously received medical treatment for diabetes but have not been treated within 6 weeks of randomization.
• BMI within the range 25 to 35 kg/m2 at screening.
• Negative pregnancy test for female subjects.
• Female subjects of childbearing potential who are sexually active with a male partner must be willing to use at least one highly effective method of contraception from screening and up to 4 weeks after the last dose of investigational product.

You may not qualify if:

• Subjects with any of the following results at screening and run-in visit
• History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures.
• Acute pancreatitis at screening or history of chronic pancreatitis or serum triglyceride levels \> 11 mmol/L (1000 mg/dL) at screening.
• Significant inflammatory bowel disease, gastroparesis or other severe disease or surgery affecting the upper GI tract (including weight-reducing surgery and procedures), which may affect gastric emptying or could affect the interpretation of safety and tolerability data.
• Significant hepatic disease (except for NASH or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening or run-in visit.
• Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN)
• Alanine transaminase (ALT) ≥ 3 × ULN
• Total bilirubin (TBL) ≥ 2 × ULN
• Impaired renal function defined as estimated glomerular filtration rate (GFR) \< 60 mL/minute/1.73m2 at screening or run-in visit (GFR estimated according to Modification of Diet in Renal Disease \[MDRD\] using MDRD Study Equation IDMS-traceable \[International System of Units (SI)\]).
• Poorly controlled hypertension defined as, For age ≤ 55 years; Systolic BP \> 140 mmHg Diastolic BP ≥ 90 mmHg For age \> 55 years; Systolic BP \> 150 mmHg Diastolic BP ≥ 90 mmHg After 10 minutes of supine rest and confirmed by repeated measurement at screening or run-in visit. Subjects who fail BP screening criteria may be considered for 24-hour or day time ABPM at the discretion of the investigator. Subjects who maintain a mean 24-hour BP \< 130/80 mmHg with a preserved nocturnal dip of \> 15% or day time BP \< 135/85 mmHg will be considered eligible
• Resting heart rate is ≥ 80 bpm at screening or run-in visit.
• Any clinically important abnormalities in rhythm, conduction, or morphology of the 12-lead ECG or any abnormalities that may interfere with the interpretation of serial ECG changes, including QTc interval changes at screening, as judged by the investigator.
• Prolonged QT intervals corrected for heart rate using Fridericia's formula (QTcF) \> 450 msec, or family history of long QT-segment at screening or run-in visit.
• PR (PQ) interval prolongation (\> 220 msec), intermittent second (Wenckebach block while asleep is not exclusive), or third-degree atrioventricular (AV) block, or AV dissociation at screening or run-in visit.
• Persistent or intermittent complete bundle branch block. A QRS duration \< 120 msec is acceptable if there is no evidence of ventricular hypertrophy or preexcitation at screening or run-in visit.

Sponsors & Collaborators

• AstraZeneca: lead
• MedImmune LLC: collaborator

Study Sites (3)

Research Site

Shinjuku-ku, 160-0008, Japan

Location

Research Site

Shinjuku-ku, 162-0053, Japan

Location

Research Site

Suita-shi, 565-0853, Japan

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

cotadutide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2019
• First Posted: December 23, 2019
• Study Start: January 21, 2020
• Primary Completion: July 8, 2020
• Study Completion: July 8, 2020
• Last Updated: July 31, 2020

Record last verified: 2020-07

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

JP (3)