A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Dose Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DD01 in Overweight/Obese Subjects With T2DM and NAFLD
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Overweight and Obesity
- Sponsor
- Neuraly, Inc.
- Enrollment
- 255
- Locations
- 4
- Primary Endpoint
- Heart Rate assessed by 24-hour ambulatory electrocardiography monitoring reader)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Phase 1, first in human (FiH), randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to investigate the safety, tolerability, PK and PD of DD01 administered by subcutaneous (SC) injection in overweight/obese subjects with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD).
The study will be conducted in 2 Parts (Part A and B), with up to 8 cohorts included in each part (Part A; Cohorts A1 to A8 and Part B; Cohorts B2 to B8).
Detailed Description
Part A (SAD): In Part A, subjects will receive a single dose of study drug, and the safety and efficacy of DD01 will be evaluated in overweight/obese subjects with T2DM. Part B (MAD): In Part B, subjects will receive once-weekly doses of the study drug for 4 weeks, and the safety and efficacy of DD01 will be evaluated in overweight/obese subjects with T2DM and NAFLD.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Type 2 diabetes ≥ 12 months.
- •Treatment with diet and exercise or metformin monotherapy on stable dose for 3 months prior to screening
- •HbA1c ≤ 10%).
- •Body Mass Index (BMI) ≥ 25 and ≤ 40.0 kg/m2
- •Part B Inclusion Criteria
- •Type 2 diabetes ≥ 12 months.
- •Treatment with diet and exercise or metformin monotherapy on stable dose for 3 months prior to screening
- •HbA1c ≤ 10%
- •BMI ≥ 30 kg/m2 and ≤ 40.0 kg/m2
- •Waist circumference ≤ 57 inches
Exclusion Criteria
- •History of type 1 diabetes mellitus (T1DM)
- •History of acute proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
- •Uncontrolled hypertension
- •Treatment with antihypertensive medication and statins not stable during the past 2 months prior to screening
- •Treatment with thyroid hormones not stable during the past 3 months prior to screening
- •History of any weight control treatment, including over-the-counter and herbal medication and supplements, or any medication with a labeled indication for weight loss or weight gain within 3 months prior to screening
- •History of surgical treatment for obesity
- •History of heart disease
- •History of renal disease
- •History or current diagnosis of acute or chronic pancreatitis or factors for pancreatitis, such as a history of cholelithiasis (without cholecystectomy) or alcohol abuse
Arms & Interventions
Group A2, Single Ascending Dose
DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: Placebo
Group B2 - Multiple Ascending Dose
DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: Placebo
Group A1 - Single Ascending Dose
DD01 Dose 1 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: DD01
Group A1 - Single Ascending Dose
DD01 Dose 1 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: Placebo
Group A2, Single Ascending Dose
DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: DD01
Group A3, Single Ascending Dose
DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: DD01
Group A3, Single Ascending Dose
DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: Placebo
Group A4, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: DD01
Group A4, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: Placebo
Group B2 - Multiple Ascending Dose
DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: DD01
Group B3 - Multiple Ascending Dose
DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: DD01
Group B3 - Multiple Ascending Dose
DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: Placebo
Group B4 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: DD01
Group B4 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: Placebo
Group B5 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: DD01
Group B5 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: Placebo
Group B6 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: DD01
Group B6 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: Placebo
Group A5, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: DD01
Group A5, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: Placebo
Group A6, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: DD01
Group A6, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: Placebo
Group A7, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: DD01
Group A7, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: Placebo
Group A8, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: DD01
Group A8, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
Intervention: Placebo
Group B7 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: DD01
Group B7 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: Placebo
Group B8 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: DD01
Group B8 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
Intervention: Placebo
Outcomes
Primary Outcomes
Heart Rate assessed by 24-hour ambulatory electrocardiography monitoring reader)
Time Frame: Part B - 57 days
Number of participants with clinically significant abnormalities in 12-lead ECGs
Time Frame: Part B - 57 days
Blood Pressure assessed by 24-hour ambulatory blood pressure monitoring (ABPM)
Time Frame: Part B - 57 days
Number of participants with treatment-related adverse events and serious adverse events
Time Frame: Part A - 43 days
Number of participants with clinically significant abnormalities in physical examinations
Time Frame: Part B - 57 days
Number of participants with clinically significant abnormalities in vital signs
Time Frame: Part B - 57 days
Number of participants with clinically significant abnormalities in clinical laboratory values
Time Frame: Part B - 57 days
Number of participants with treatment-related adverse events and serious adverse events (TEAEs)
Time Frame: Part B - 57 days
Secondary Outcomes
- Maximum observed blood/plasma concentration of DD01(Part B - 57 days)
- Termination elimination rate constant of DD01(Part B - 57 days)
- Apparent total blood/plasma clearance of DD01(Part B - 57 days)
- Time of the maximum observed blood/plasma concentration of DD01(Part B - 57 days)
- Apparent blood/plasma terminal elimination half life of DD01(Part B - 57 days)
- Area under the blood/plasma concentration time curve from time zero to 216 hours postdose of DD01(Part B - 57 days)
- Area under the blood/plasma concentration time curve from time zero to 168 hours postdose of DD01(Part B - 57 days)
- Apparent volume of distribution of DD01(Part B - 57 days)
- Area under the blood/plasma concentration time curve from time zero to 144 hours postdose of DD01(Part B - 57 days)
- Area under the blood/plasma concentration time curve from time zero to the time of the last quantifiable concentration of DD01(Part B - 57 days)
- Number of participants with antidrug antibodies (ADAs)(Part B - 57 days)