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

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

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.

Study Overview

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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32804
      • Investigational Site Number 8400001
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Investigational Site Number 8400002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2018
• Primary Completion (Actual): December 27, 2018
• Study Completion (Actual): December 27, 2018

Study Registration Dates

• First Submitted: December 12, 2017
• First Submitted That Met QC Criteria: December 12, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 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; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: PDY15012; U1111-1191-5658 (Other Identifier: 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
• product manufactured in and exported from the U.S.: Yes