Chinese Multiple Dose Escalation (MDE) High Dose Study
- Conditions
- Diabetes
- Interventions
- Other: Placebo
- Registration Number
- NCT05437848
- Lead Sponsor
- AstraZeneca
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo: Placebo subcutaneous injection
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events (TEAEs) Baseline until the follow-up period (28 days post last dose), 98 days in total To assess the safety and tolerability of Cotadutide
Incidence of treatment-emergent serious adverse events (TESAEs) Baseline until the follow-up period (28 days post last dose), 98 days in total To assess the safety and tolerability of Cotadutide
Time to Cmax (tmax) Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days. To characterize the PK profile of Cotadutide
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Baseline until the follow-up period (28 days post last dose), 98 days in total 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.
Number of participants with abnormal vital signs reported as TEAEs 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 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).
Number of Participants With Abnormal Physical Examinations Reported as TEAEs 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 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.
Area under the concentration-time curve (AUC) during the dosing interval (AUCtau) Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days. To characterize the PK profile of Cotadutide
Maximum observed concentration (Cmax) Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days. To characterize the PK profile of Cotadutide
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Baseline until the follow-up period (28 days post last dose), 98 days in total 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.
Trough plasma concentration (Ctrough) Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days. To characterize the PK profile of Cotadutide
- Secondary Outcome Measures
Name Time Method 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. To assess the effect of Cotadutide on glucose control as measured by continuous glucose monitoring (CGM)
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 To assess the effect of Cotadutide on glucose control as measured by continuous glucose monitoring (CGM)
Change in fasting plasma glucose (mg/dL) Baseline through 21day treatment extension period, 70 days in total To assess the effects of cotadutide, titrated up to the dose of 600 μg, on additional measures of glucose control
Change in HbA1c Baseline through 21day treatment extension period, 70 days in total To assess the effects of cotadutide, titrated up to the dose of 600 μg, on additional measures of glucose control
Anti-drug antibodies (ADAs) to Cotadutide Day 1 of Up-titration treatment period through end of study, 98 days in total To characterize the immunogenicity of Cotadutide
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 To assess the effect of Cotadutide on glucose control as measured by continuous glucose monitoring (CGM)
Absolute change in body weight Baseline through 21day treatment extension period, 70 days in total To assess the effects of cotadutide, titrated up to the dose of 600 μg, on body weight
Proportion of subjects achieving > 5% body weight loss Baseline through 21day treatment extension period, 70 days in total To assess the effects of cotadutide, titrated up to the dose of 600 μg, on body weight
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 To assess the effect of Cotadutide on glucose control as measured by continuous glucose monitoring (CGM)
Change in percentage time spent in the range (< 54 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 To assess the effect of Cotadutide on glucose control as measured by continuous glucose monitoring (CGM)
Change in estimated hemoglobin A1c (HbA1c) Baseline through 21day treatment extension period, 70 days in total To assess the effect of Cotadutide on glucose control as measured by continuous glucose monitoring (CGM)
Percentage change in body weight Baseline through 21day treatment extension period, 70 days in total To assess the effects of cotadutide, titrated up to the dose of 600 μg, on body weight
Change in coefficient of variation as measured by CGM over 7 days 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 To assess the effect of Cotadutide on glucose control as measured by continuous glucose monitoring (CGM)
Trial Locations
- Locations (1)
Research Site
🇨🇳Nanjing, China