A Study to Assess the Safety and Efficacy of SAR425899 in Patients With Type 2 Diabetes Mellitus
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT02973321
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
The primary objective of this study was to assess the dose-response relationship of SAR425899 versus placebo in terms of glycemic control as measured by the change in glycosylated hemoglobin (HbA1c).
Secondary Objectives:
* To assess the effect of SAR425899 on body weight.
* To assess the safety and immunogenicity profile of SAR425899, including assessment of the heart rate (HR) change by electrocardiogram (ECG) and Holter monitor.
* To assess the proportion of participants achieving predefined HbA1c targets of \<7% and \<6.5% as well as the proportion of participants achieving \>=5% and \>=10% body weight loss.
* To assess the effect of once daily dosing of SAR425899 on additional parameters of glycemic control and lipid metabolism.
* To assess the effect of once daily dosing of SAR425899 on additional pharmacodynamic (PD) biomarkers.
* To assess the pharmacokinetic (PK) profile and parameters of SAR425899, inter-individual and inter-occasion variability in PK parameters using a population PK approach.
- Detailed Description
The total study duration will be approximately 30 weeks, consisting of 3 weeks screening period at the site, a 26 weeks treatment period, and 3 days post treatment follow up period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 296
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo (for SAR425899) subcutaneous (SC) injection once daily (QD) from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg. SAR425899 0.12 mg SAR425899 SAR425899 SC injection QD at maintenance dose of 0.12 mg for 25 weeks (Week 2 to Week 26) following 1 week dose increase step (0.06 mg at Week 1). SAR425899 0.20 mg SAR425899 SAR425899 SC injection QD at maintenance dose of 0.20 mg for 23 weeks (Week 4 to Week 26) following 3 weeks dose increase step (0.06 mg at Week 1, 0.12 mg at Week 2 and 0.16 mg at Week 3). SAR425899 0.16 mg SAR425899 SAR425899 SC injection QD at maintenance dose of 0.16 mg for 24 weeks (Week 3 to Week 26) following 2 weeks dose increase step (0.06 mg at Week 1 and 0.12 mg at Week 2). SAR425899 0.16 mg Metformin SAR425899 SC injection QD at maintenance dose of 0.16 mg for 24 weeks (Week 3 to Week 26) following 2 weeks dose increase step (0.06 mg at Week 1 and 0.12 mg at Week 2). Placebo Metformin Placebo (for SAR425899) subcutaneous (SC) injection once daily (QD) from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg. SAR425899 0.12 mg Metformin SAR425899 SC injection QD at maintenance dose of 0.12 mg for 25 weeks (Week 2 to Week 26) following 1 week dose increase step (0.06 mg at Week 1). SAR425899 0.20 mg Metformin SAR425899 SC injection QD at maintenance dose of 0.20 mg for 23 weeks (Week 4 to Week 26) following 3 weeks dose increase step (0.06 mg at Week 1, 0.12 mg at Week 2 and 0.16 mg at Week 3). Liraglutide Liraglutide Liraglutide SC injection QD at maintenance dose of 1.8 mg for 24 weeks (Week 3 to Week 26) following 2 weeks dose increase steps (0.6 mg daily at Week 1 and by 1.2 mg daily at Week 2). Liraglutide Metformin Liraglutide SC injection QD at maintenance dose of 1.8 mg for 24 weeks (Week 3 to Week 26) following 2 weeks dose increase steps (0.6 mg daily at Week 1 and by 1.2 mg daily at Week 2).
- Primary Outcome Measures
Name Time Method Change From Baseline in HbA1c to Week 26 Baseline, Week 26 Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Missing post-baseline values were imputed by placebo control-based multiple imputation (MI) method under the missing not at random framework.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Average 7 Point Self-Monitoring Plasma Glucose (SMPG) to Week 26 Baseline, Week 26 Change in 7-point SMPG profile from baseline to Week 26 was assessed by summary statistics. 7-point SMPG profiles were measured at the following 7 points at each visit (Baseline, and Week 26): pre-prandial and 2 hours postprandial for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) is defined as 2 hours after the start of the meal.
Percentage of Participants Requiring Rescue Therapy Baseline up to 26 weeks Rescue medication was introduced in case FPG or HbA1c values were above pre-defined thresholds, and if no reasons were found for insufficient glucose control, and appropriate action failed to decrease FPG / HbA1c under the threshold values (from baseline to Week 8: FPG \>270 mg/dL 15.0 mmol/L, from Week 8 to Week 14: FPG \>13.3 mmol/L, and from Week 14 to Week 26: FPG \>11.1 mmol/L or HbA1c\>8%). The choice of rescue therapy was at the Investigator's discretion with the exception of using glucagon-like peptide-1 receptor (GLP-1R) agonists or dipeptidyl peptidase 4 (DPP4) inhibitors.
Change From Baseline in Beta-Cell Function to Week 26 Baseline, Week 26 Beta-cell function was assessed by homeostatic model assessment (HOMA)-beta, derived from FPG and fasting plasma insulin (FPI). HOMA-beta was derived from FPG and FPI as (20\*FPI \[micro units/milliliter\]) divided by (FPG \[mmol/L\] minus 3.5). Change was calculated for HOMA-beta by subtracting the Baseline value from Week 26 value\*100.
Change From Baseline in Insulin Resistance to Week 26 Baseline, Week 26 Insulin Resistance was assessed by homeostasis model assessment for insulin resistance (HOMA-IR), derived from FPG and FPI. HOMA-IR was derived from FPG and FPI as (FPI \[micro units per milliliter\] \* FPG \[mmol/L\]) divided by 22.5. Change was calculated for HOMA-beta by subtracting the Baseline value from Week 26 value.
Change From Baseline in Pharmacodynamic Biomarkers to Week 26 - Waist and Hip Circumferences Baseline,Week 26 Waist circumference was measured at the midpoint between the lower margin of the least palpable rib and the top of the iliac crest, using a stretch-resistant tape providing a constant 100 gm tension. Hip circumference was measured around the widest portion of the buttocks, with the tape parallel to the floor. Each measurement was repeated twice; if the measurements were within 1 cm of one another, the average was calculated, and if the difference exceeded 1 cm, the measurements were repeated.
Mean Change From Baseline in Body Weight to Week 26 Baseline, Week 26 Change in body weight was calculated by subtracting baseline value from Week 26 value. Missing post- baseline values were imputed by placebo control-based MI method under the missing not at random framework.
Percentage of Participants Reached HbA1c Target of <6.5% or <7% at Week 26 Week 26 The analysis included assessment collected during the study, including those obtained after IMP discontinuation or introduction of rescue therapy. Participants with no measurement at Week 26 were treated as non-responders.
Percentage of Participants Achieving >=5% or >=10% Body Weight Loss at Week 26 Week 26 The analysis included assessment collected during the study, including those obtained after IMP discontinuation or introduction of rescue therapy. Participants with no measurement at Week 26 were treated as non-responders.
Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26 Baseline, Week 26 Change in FPG was calculated by subtracting baseline value from Week 26 value. Missing post-baseline values were imputed by placebo control-based MI method under the missing not at random framework.
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Trial Locations
- Locations (59)
Investigational Site Number 8400028
🇺🇸Sheffield, Alabama, United States
Investigational Site Number 8400002
🇺🇸Huntington Park, California, United States
Investigational Site Number 8400024
🇺🇸Los Angeles, California, United States
Investigational Site Number 8400001
🇺🇸Los Angeles, California, United States
Investigational Site Number 8400012
🇺🇸Port Hueneme, California, United States
Investigational Site Number 8400027
🇺🇸Denver, Colorado, United States
Investigational Site Number 8400025
🇺🇸Miami, Florida, United States
Investigational Site Number 8400007
🇺🇸Palm Harbor, Florida, United States
Investigational Site Number 8400013
🇺🇸Chicago, Illinois, United States
Investigational Site Number 8400016
🇺🇸Wichita, Kansas, United States
Scroll for more (49 remaining)Investigational Site Number 8400028🇺🇸Sheffield, Alabama, United States