Chinese Multiple Dose Escalation (MDE) High Dose Study

NCT ID: NCT05437848

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-25
• Study Completion Date: 2022-12-12

Brief Summary

A Phase 1 Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Cotadutide in Overweight/Obese Subjects with Chinese ancestry with Type 2 Diabetes Mellitus

Detailed Description

This is a randomized, double-blinded, placebo-controlled study designed to evaluate the safety, tolerability, PK and efficacy of ascending doses of cotadutide in overweight or obese subjects with T2DM. This study will enroll subjects aged 18 to 74 years with a body mass index (BMI) ≥ 25 and ≤ 35 kg/m2. Subjects will have a diagnosis of T2DM and inadequate blood glucose control as defined by a HbA1c of 7% to 8.5%, and will be on metformin monotherapy in the three months prior to screening. Total 16 Chinese subjects will be randomized to cotadutide or placebo in a 3:1 ratio (cotadutide [n=12] and placebo [n=4]) at multicentre in China mainland. Those subjects who receive cotadutide once daily SC will be titrated to a maximum of 600 μg once daily SC, beginning at 50 μg once daily SC. The study has about 2 weeks screening period, a run-in period of 10 days and an up to 7-week up-titration treatment period followed by a 3-week treatment extension period at the dose of 600 μg and followed by a 28-day follow-up period.

Conditions

Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Cotadutide

Those subjects who were randomized to cotadutide once daily SC will begin at 50 μg once daily, then up-titrated to 100 μg once daily a week later, after that up-titration will be done at 100 μg increment weekly, till to a maximum of 600 μg once daily.

Group Type: EXPERIMENTAL

Experimental: Cotadutide

Intervention Type: DRUG

Cotadutide: subcutaneous (SC) injection

Placebo

Placebo: Placebo subcutaneous injection

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo subcutaneous injection

Interventions

Experimental: Cotadutide

Cotadutide: subcutaneous (SC) injection

Intervention Type: DRUG

Placebo

Placebo subcutaneous injection

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Subjects aged 18 to 74 years

2. Provision of signed and dated written informed consent prior to any study specific procedures

3. BMI between 25 and 35 kg/m2

4. HbA1c range of 7% to 8.5%

5. Willing and able to self-inject investigational product

6. Diagnosed with T2DM with glucose control managed with metformin monotherapy where no significant dose change has occurred in the three months prior to screening.

7. Women of child-bearing potential who are sexually active with a male partner must be using at least one highly effective method of contraception. And must have a negative serum or urine pregnancy test within 72 hours prior to the start of IP, and must not be breastfeeding.

Exclusion Criteria

1. Any subject who has received another IP as part of a clinical study or a GLP-1 analogue containing preparation within the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening

2. Concurrent participation in another randomization study of any kind; repeat randomization is prohibited

3. Any subject who has received any of the following medications within the specified timeframe prior to the start of the study

• Herbal preparations for control of body weight or appetite
• Drugs licensed for control of body weight or appetite
• Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying
• Antimicrobials within the quinolone (eg, ciprofloxacin), macrolide (eg, clarithromycin) or azole class (eg, ketoconazole)
• Any change in antihypertensive medication
• Aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily
• Paracetamol (acetaminophen) or paracetamol-containing preparations at a total daily dose of greater than 3000 mg
• Ascorbic acid (vitamin C) supplements at a total daily dose of greater than 1000 mg

4. Symptoms of acutely decompensated blood glucose control, recent severe hypoglycemia, a history of T1DM orDKA

5. Acute pancreatitis at screening or history of acute pancreatitis or chronic pancreatitis or serum triglyceride levels > 11 mmol/L at screening

6. Significant inflammatory bowel disease, gastroparesis or other severe disease or surgery affecting the upper GI tract, which may affect gastric emptying or could affect the interpretation of safety and tolerability data

7. Significant hepatic disease (except for NASH or NAFLD without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening:

• AST ≥ 3 × ULN
• ALT ≥ 3 × ULN
• TBL ≥ 2 × ULN

8. Impaired renal function defined as eGFR< 30 mL/minute/1.73m2 at screening

9. Poorly controlled hypertension defined as:

• SBP > 160 mmHg
• DBP or ≥ 90 mmHg - After 10 minutes of supine rest and confirmed by repeated measurement at screening. Subjects who fail BP screening criteria may be considered for 24-hour ABPM at the discretion of the investigator. Subjects who maintain a mean 24-hour BP < 160/100 mmHg with a preserved nocturnal dip of > 15% will be considered eligible.

10. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 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, and prolonged QTcF > 450 ms, or family history of long QT-segment at screening

11. PR (PQ) interval prolongation, intermittent second (Wenckebach block while asleep is not exclusive), or third-degree AV block, or AV dissociation

12. Persistent or intermittent complete bundle branch block.

13. Unstable angina pectoris, myocardial infarction, transient ischemic attack, or stroke within 3 months prior to screening, or subjects who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening

14. Severe congestive heart failure (NYHA Class III or IV)

15. Basal calcitonin level ≥ 50 ng/L at screening or history/family history of medullary thyroid carcinoma or MEN2

16. 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

17. Any positive results for serum hepatitis B surface antigen, hepatitis C antibody, and HIV antibody

18. History of substance dependence, alcohol abuse, or excessive alcohol intake within 3 years prior to screening and/or a positive screen for drugs of abuse or alcohol at screening or on admission to the study unit.

19. Symptoms of depression or any other psychiatric disorder requiring treatment with medication (eg, anti-depressants, anti-psychotics) at screening. However, subjects who use benzodiazepines for chronic anxiety or sleep disorders may be permitted to enter the study.

20. History of severe allergy/hypersensitivity, including to any component of the investigational product formulation or other biological agent, or ongoing clinically important allergy/hypersensitivity as judged by the investigator

21. Blood/plasma donation within 1 month of screening

22. Involvement of any AstraZeneca, the contract research organization, or the virtual study site employee or their close relatives

23. For women only- currently pregnant (confirmed with positive pregnancy test) or breastfeeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Guangzhou, , China

Research Site

Nanjing, , China

Countries

China

Other Identifiers

D5671C00005

Identifier Type: -

Identifier Source: org_study_id