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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: SAR425899

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55144
      • Investigational Site Number 8400002
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Investigational Site Number 8400003
  • Texas
    • Austin, Texas, United States, 78744
      • Investigational Site Number 8400001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; 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; Pharmaceutical form: Solution Route of administration: Subcutaneous
EXPERIMENTAL: Cohort 2; 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; Pharmaceutical form: Solution Route of administration: Subcutaneous
EXPERIMENTAL: Cohort 3; 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; Pharmaceutical form: Solution Route of administration: Subcutaneous

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 19, 2018
• Primary Completion (ACTUAL): October 5, 2018
• Study Completion (ACTUAL): October 5, 2018

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: January 23, 2018
• First Posted (ACTUAL): January 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight
• Other Study ID Numbers: TDR15516; U1111-1205-1368 (OTHER: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No