A Clinical Study to Investigate the Effect of SAR425899 on Energy Expenditure in Obese Subjects

Study Overview
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Brief Summary
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Primary Objective: To assess in overweight to obese subjects the change in sleep energy expenditure after repeated subcutaneous (SC) doses of SAR425899. Secondary Objectives: To assess the change in resting, basal and total daily energy expenditure. To assess the change in respiratory quotient, fat, protein and carbohydrate oxidation. To assess the change in body composition and core temperature. To assess the pharmacodynamic effects on fasting plasma glucose, biomarkers of lipid metabolism and glycated hemoglobin (HbA1c). To assess the pharmacokinetic parameters for SAR425899 after repeated SC doses. To assess the safety and tolerability.

Detailed Description
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Study duration is approximately 7-8 weeks including a screening period, a 19-day treatment period and an end-of-study visit 7 days after last dosing.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Assess the Effect of Repeated Subcutaneous Doses of SAR425899 on Energy Expenditure and Safety in Overweight to Obese Male and Female Subjects

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: SAR425899
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Overweight to obese male and female subjects. Body mass index 28 - 40 kg/m2. 18 to 50 years of age Fasting plasma glucose ≤125 mg/dL. Glycated hemoglobine (HbA1c) ≤6.5%. Obesity associated mild concomitant diseases allowed (eg, mild hypertension, mild hypercholesteremia, and hyperlipidemia). No concomitant medication allowed except stable treatment with statins or antihypertensive drugs (except ß-blocker). Females should be either postmenopausal, or, if perimenopausal should have a normal regular menstrual cycle and should start or continue stable treatment with a monophasic oral contraceptive. Exclusion criteria: Elevated liver enzymes, lipase, amylase, or calcitonin at screening. Current participation in an organized diet / weight reduction program or clinical trial of weight control or weight loss attempt, plans for major changes in physical activities or significant change in body weight in the 2 months prior to screening. Any condition possibly affecting gastric emptying or absorption from gastro-intestinal tract (eg, gastric surgery, gastrectomy, bariatric surgery, malabsorption syndromes, gastroparesis, abdominal surgery other than appendectomy or hysterectomy. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR425899<br>Repeated once daily subcutaneous (SC) doses of SAR425899 administered over 19 days | Drug: SAR425899<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous<br>|
| Placebo Comparator: Placebo<br>Repeated once daily SC doses of placebo administered over 19 days | Drug: Placebo<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep energy expenditure | Change of sleep energy expenditure from baseline to Day 19 with SAR425899 or placebo | Baseline to Day 19 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total daily energy expenditure | Change of total energy expenditure from baseline to Day 19 with SAR425899 or placebo | Baseline to Day 19 | 
| Resting energy expenditure | Change of resting energy expenditure from baseline to Day 19 with SAR425899 or placebo | Baseline to Day 19 | 
| Basal energy expenditure | Change of basal energy expenditure from baseline to Day 19 with SAR425899 or placebo | Baseline to Day 19 | 
| Respiratory quotient (RQ) | Change of respiratory quotient from baseline to Day 19 with SAR425899 or placebo | Baseline to Day 19 | 
| Fat mass and fat-free mass | Change of fat mass and fat-free mass by dual energy X-ray absorptiometry (DEXA) scan from baseline to Day 20 with SAR425899 or placebo | Baseline to Day 20 | 
| Diet Induced Thermogenesis (DIT) | Change of DIT from baseline to Day 19 with SAR425899 or placebo | Baseline to Day 19 | 
| Fasting plasma glucose | Change of FPG over time with SAR425899 or placebo | 20 days | 
| HbA1c | Change of HbA1c from baseline to Day 20 with SAR425899 or placebo | Baseline to Day 20 | 
| Lipid biomarker (free fatty acids, triglycerides, total cholesterol, HDL-/LDL-cholesterol) | Change of lipid biomarkers over time with SAR425899 or placebo | 20 days | 
| Ketone bodies | Change of ketone bodies over time with SAR425899 or placebo | 20 days | 
| Adverse events | Number of adverse events in patients under treatment with SAR425899 or placebo | Up to 27 days | 
| Pharmacokinetics | Assessment of SAR425899: time to reach Cmax (tmax) | Day 16 | 
| Pharmacokinetics | Assessment of SAR425899: maximum plasma concentration (Cmax) | Day 16 | 
| Pharmacokinetics | Assessment of SAR425899: area under the concentration versus time curve (AUC) | Day 16 | 
| Pharmacokinetics | Assessment of SAR425899: terminal elimination half-life (t1/2) | Day 16 |