A Study on Safety and Tolerability of SAR425899 in Overweight to Obese Subjects and Type 2 Diabetes Mellitus Patients Not Requiring Anti-Diabetic Pharmacotherapy With an Optional 6-month Safety Extension Period

Study Overview
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Brief Summary
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Primary Objectives: Main study: To assess in overweight to obese subjects and type 2 diabetes mellitus (T2DM) patients not requiring anti-diabetic pharmacotherapy the safety and tolerability of 3 different dose escalation regimens of SAR425899 in terms of the relative and absolute frequency and severity of gastrointestinal (GI) adverse events (AEs). Six-month safety extension period: To assess the safety and tolerability of SAR425899 after 6 months treatment at the maximum dose that was individually well tolerated during the main part of the study in terms of the relative and absolute frequency and severity of GI AEs. Secondary Objectives: Main study and 6-month study extension period: To assess in overweight to obese subjects and T2DM patients not requiring anti-diabetic pharmacotherapy: The effect of once-daily dosing of SAR425899 on body weight (BW), fasting plasma glucose (FPG), and hemoglobin A1c (HbA1c). Safety and tolerability.

Detailed Description
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Main study: The maximum study duration is approximately 12 weeks per patient (up-to 3-week screening period, 8-week treatment period, 3-day post treatment follow-up period). Six-month study extension period: The maximum study duration is approximately 9 months (up-to 3-week screening period, 8-month treatment period, 3-day post treatment follow-up period).

Official Title
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A Randomized, Comparative, Open Label Study to Assess the Safety and Tolerability of 3-arm, Parallel, Repeated Subcutaneous Dose Regimens of SAR425899 in Overweight to Obese Subjects and T2DM Patients Not Requiring Anti-diabetic Pharmacotherapy, With an Optional 6-month Safety Extension Period

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: SAR425899


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female overweight to obese subjects and type 2 diabetes mellitus (T2DM) patients not requiring anti-diabetic pharmacotherapy. Patients who are motivated to lose weight. Exclusion criteria: Type 1 diabetes mellitus. Body mass index <27 kg/m2. Screening hemoglobin A1c (HbA1c; glycosylated hemoglobin) >7.0%. Previous treatment with glucose-lowering agent(s) (eg, insulin, thiazolidinediones, metformin, DPP-IV inhibitors (dipeptidylpeptidase 4), SGLT-2 (sodium dependent glucose transporter-2) inhibitors, etc) within the last 6 months. Previous treatment with glucagon-like peptide 1 (GLP-1) receptor agonists within the last 6 months. Uncontrolled hypertension. Laboratory findings at the time of screening: amylase and/or lipase >2 times the upper limit of the normal laboratory range (ULN), alanine aminotransferase >1.5 ULN, total bilirubin >1.5 ULN, serum creatinine levels ≥1.5 mg/dL [males]. ≥1.4 mg/dL [females], screening calcitonin ≥20 pmol/m, fasting serum triglycerides >400 mg/dL. Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC. History of weight loss surgery. History of pancreatitis or pancreatectomy. Pregnant or lactating women. Women of childbearing potential (WOCBP) not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy. 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: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Daily dose escalation (click-by-click): Starting at dose 1 in the morning with daily increments to dose 2. During the escalation phase, the dose will only be increased if the patient is feeling fine. | Drug: SAR425899<br>* Pharmaceutical form: Solution Route of administration: Subcutaneous<br>|
| Experimental: Cohort 2<br>Weekly dose escalation in 6 escalation steps (7 dose levels): Starting at dose 1 injected in the morning with weekly increments to dose 2. In case a dose level is not well tolerated by a patient, the treatment should continue at the same dose level for another 7 days before the next dose escalation. | Drug: SAR425899<br>* Pharmaceutical form: Solution Route of administration: Subcutaneous<br>|
| Experimental: Cohort 3<br>Weekly dose escalation in 4 escalation steps (5 dose levels): Starting at dose 3 with weekly increments to dose 2. In case a dose level is not well tolerated by a patient, the treatment should continue at the same dose level for another 7 days before the next dose escalation. | Drug: SAR425899<br>* Pharmaceutical form: Solution Route of administration: Subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of gastrointestinal (GI) adverse events (AEs) | Relative frequency of GI AEs | Main study: Up to week 8; Six-month study extension period: Up to month 8 | 
| Frequency of GI AEs | Absolute frequency of GI AEs | Main study: Up to week 8; Six-month study extension period: Up to month 8 | 
| Frequency of GI AEs | Severity of GI AEs | Main study: Up to week 8; Six-month study extension period: Up to month 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | Change in body weight from baseline to week 8 for the main study and from baseline to month 8 for the study extension period. | Main study: Baseline (D1) to week 8; Six-month study extension period: Baseline (D1) up to month 8 | 
| Change in fasting plasma glucose (FPG) | Change in FPG from baseline to week 8 for the main study and from baseline to month 8 for the study extension period. | Main study: Baseline (D1) to week 8; Six-month study extension period: Baseline (D1) up to month 8 | 
| Change in hemoglobin A1c (HbA1c) | Change in HbA1c from baseline to week 8 for the main study and from baseline to month 8 for the study extension period. | Main study: Baseline (D1) to week 8; Six-month study extension period: Baseline (D1) up to month 8 | 
| Adverse events (AEs) | Number of AEs | Main study: up to week 8; Six-month extension period: up to month 8 |