Chinese Multiple Dose Escalation (MDE) High Dose Study

NCT05437848 | Completed Phase 1

• 1 other identifier: D5671C00005
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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

Conditions

Diabetes

Keywords

Diabetes; Cotadutide; MEDI0382; D5671C00005; Type 2 Diabetes mellitus; Obesity; Overweight

Outcome Measures

Primary Outcomes (10)

• 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), 98 days in total

• 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), 98 days in total

• Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs

  Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals as measured by digitial 12-lead ECG.

  Baseline until the follow-up period (28 days post last dose), 98 days in total

• Number of participants with abnormal vital signs reported as TEAEs

  Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital sign parameters (Systolic Blood Pressure, Diastolic Blood Pressure, Pulse, Respiration rate, body temperature).

  Baseline until the follow-up period (28 days post last dose), 98 days in total

• Number of Participants With Abnormal Physical Examinations Reported as TEAEs

  Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examinations findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and enocrine.

  Baseline until the follow-up period (28 days post last dose), 98 days in total

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

  To characterize the PK profile of Cotadutide

  Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days.

• Maximum observed concentration (Cmax)

  To characterize the PK profile of Cotadutide

  Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days.

• Time to Cmax (tmax)

  To characterize the PK profile of Cotadutide

  Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days.

• Trough plasma concentration (Ctrough)

  To characterize the PK profile of Cotadutide

  Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days.

• Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

  Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urinalysis.

  Baseline until the follow-up period (28 days post last dose), 98 days in total

Secondary Outcomes (13)

• Anti-drug antibodies (ADAs) to Cotadutide

  Day 1 of Up-titration treatment period through end of study, 98 days in total

• Change in daily average glucose levels

  baseline to the end of extension period, and during 14 days of the follow up period, 84 days in total.

• Change in 7-day average glucose levels

  Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49 of the up-titration period, Days 50-56, Days 57-63, Days 64 - 70 of the treatment extension period

• Change in percentage time spent in hyperglycemia (> 140 mg/dL) over 24hours and over 7days

  Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49 of the up-titration period, Days 50-56, Days 57-63, Days 64 - 70 of the treatment extension period

• Change in percentage time spent in target range (70 -140 mg/dL) over 24hours and over 7days

  Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49 of the up-titration period, Days 50-56, Days 57-63, Days 64 - 70 of the treatment extension period

Study Arms (2)

Cotadutide

EXPERIMENTAL

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.

Drug: Experimental: Cotadutide

Placebo

PLACEBO COMPARATOR

Placebo: Placebo subcutaneous injection

Other: Placebo

Interventions

Experimental: Cotadutide DRUG

Cotadutide: subcutaneous (SC) injection

Cotadutide

Placebo OTHER

Placebo subcutaneous injection

Placebo

Eligibility Criteria

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

You may qualify if:

• Subjects aged 18 to 74 years
• Provision of signed and dated written informed consent prior to any study specific procedures
• BMI between 25 and 35 kg/m2
• HbA1c range of 7% to 8.5%
• Willing and able to self-inject investigational product
• Diagnosed with T2DM with glucose control managed with metformin monotherapy where no significant dose change has occurred in the three months prior to screening.
• 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.

You may not qualify if:

• 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
• Concurrent participation in another randomization study of any kind; repeat randomization is prohibited
• 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
• Symptoms of acutely decompensated blood glucose control, recent severe hypoglycemia, a history of T1DM orDKA
• Acute pancreatitis at screening or history of acute pancreatitis or chronic pancreatitis or serum triglyceride levels \> 11 mmol/L at screening
• 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
• Significant hepatic disease (except for NASH or NAFLD without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening:

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Guangzhou, 510515, China

Location

Research Site

Nanjing, 210012, China

Location

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2; Obesity; Overweight

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Total 16 Chinese subjects will be randomized to cotadutide or placebo in a 3:1 ratio (cotadutide \[n=12\] and placebo \[n=4\]) at multicenter in China mainland.

Study Record Dates

• First Submitted: February 23, 2022
• First Posted: June 29, 2022
• Study Start: February 25, 2022
• Primary Completion: December 12, 2022
• Study Completion: December 12, 2022
• Last Updated: November 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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 deidentified 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

CN (2)