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

• ClinicalTrials.gov Identifier: NCT03414736
• Recruitment Status: Completed
• First Posted: January 30, 2018
• Last Update Posted: April 25, 2022
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Drug: SAR425899	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 19, 2018
• Actual Primary Completion Date: October 5, 2018
• Actual Study Completion Date: October 5, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Frequency of gastrointestinal (GI) adverse events (AEs) [ Time Frame: Main study: Up to week 8; Six-month study extension period: Up to month 8 ]
   Relative frequency of GI AEs
2. Frequency of GI AEs [ Time Frame: Main study: Up to week 8; Six-month study extension period: Up to month 8 ]
   Absolute frequency of GI AEs
3. Frequency of GI AEs [ Time Frame: Main study: Up to week 8; Six-month study extension period: Up to month 8 ]
   Severity of GI AEs

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Minnesota

Investigational Site Number 8400002

Saint Paul, Minnesota, United States, 55144

United States, Tennessee

Investigational Site Number 8400003

Knoxville, Tennessee, United States, 37920

United States, Texas

Investigational Site Number 8400001

Austin, Texas, United States, 78744

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT03414736
• Other Study ID Numbers: TDR15516; U1111-1205-1368 ( Other Identifier: UTN )
• First Posted: January 30, 2018
• Last Update Posted: April 25, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight