A Study to Assess the Safety and Efficacy of SAR425899 in Patients With Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A 26-Week Randomized, Double-blind, Placebo-controlled, Dose-ranging Phase 2 Study to Assess the Safety and Efficacy of SAR425899 in Patients With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02973321
• Other study ID #: DRI13940
• Secondary ID: 2016-001328-77U1
• Status: Completed
• Phase: Phase 2
• Start date: December 2, 2016
• Est. completion date: December 27, 2017

Study information

• Verified date: March 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

The primary objective of this study was to assess the dose-response relationship of SAR425899 versus placebo in terms of glycemic control as measured by the change in glycosylated hemoglobin (HbA1c).

Secondary Objectives:

• To assess the effect of SAR425899 on body weight.

• To assess the safety and immunogenicity profile of SAR425899, including assessment of the heart rate (HR) change by electrocardiogram (ECG) and Holter monitor.

• To assess the proportion of participants achieving predefined HbA1c targets of <7% and <6.5% as well as the proportion of participants achieving >=5% and >=10% body weight loss.

• To assess the effect of once daily dosing of SAR425899 on additional parameters of glycemic control and lipid metabolism.

• To assess the effect of once daily dosing of SAR425899 on additional pharmacodynamic (PD) biomarkers.

• To assess the pharmacokinetic (PK) profile and parameters of SAR425899, inter-individual and inter-occasion variability in PK parameters using a population PK approach.

Description:

The total study duration will be approximately 30 weeks, consisting of 3 weeks screening period at the site, a 26 weeks treatment period, and 3 days post treatment follow up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 296
• Est. completion date: December 27, 2017
• Est. primary completion date: December 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion criteria :

• Participants with type-2 diabetes mellitus (T2DM) for at least 3 months before the screening visit.

• On diet/exercise and/or treatment with metformin (stable dose of =1500 mg/day or maximal tolerated dose) for at least 3 months prior to screening.

• Signed informed consent.

Exclusion criteria:

• At screening, participant's age < legal age of adulthood and >80 years.

• Glycated hemoglobin at screening visit <7.0% or >10.0%.

• Body mass index (BMI) <25 kg/m^2 or >45.0 kg/m^2.

• 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.

• Diagnosis of type 1 diabetes mellitus.

• Fasting plasma glucose of >15 mmol/L (270 mg/dL) measured by the central laboratory at screening (Visit 1), and confirmed (>15 mmol/L [270 mg/dL]) by a repeat test before randomization.

• Treatment with glucose-lowering agents(s) other than metformin, currently or within the 3 months prior to screening.

• Previous insulin use, except for episode(s) of short-term treatment (=15 consecutive days) for intercurrent illness or pregnancy, or use of insulin within the last 6 months.

• Contraindication(s) to metformin use.

• Contraindication(s) to liraglutide use.

• Significant change in body weight in the 3 months before screening.

• Poorly controlled hypertension (a resting systolic blood pressure (SBP) >160 mm Hg and/or diastolic blood pressure (DBP) >95 mm Hg at screening).

• History of long QT syndrome and/or QTc more than 450 ms at screening visit.

• History of pancreatitis or pancreatectomy.

• History of weight loss surgery.

• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC.

• Any prior exposure to drugs belonging to the class of glucagon-like peptide-1 (GLP-1) receptor agonists/GLP-1 analogs.

• Contraindications or known hypersensitivity reaction to glucagon.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• SAR425899
Self-administered by SC injection using a solution for injection in cartridge.
• Placebo
Self-administered by SC injection using a solution for injection in cartridge.
• Liraglutide
Self-administered by SC injection using a pre-filled pen.
• Metformin
Orally administered at a stable dose , >=1500 mg daily stable dose or maximal tolerated dose.

Locations

Country	Name	City	State
Canada	Investigational Site Number 1240008	Quebec
Canada	Investigational Site Number 1240005	Sainte-Foy
Canada	Investigational Site Number 1240002	Sherbrooke
Canada	Investigational Site Number 1240001	Toronto
Canada	Investigational Site Number 1240003	Vancouver
Czechia	Investigational Site Number 2030003	Ceske Budejovice
Czechia	Investigational Site Number 2030001	Krnov
Czechia	Investigational Site Number 2030004	Praha 10 - Uhrineves
Czechia	Investigational Site Number 2030002	Praha 9 - Klanovice
Germany	Investigational Site Number 2760003	Berlin
Germany	Investigational Site Number 2760001	Dresden
Germany	Investigational Site Number 2760006	Hohenmölsen
Hungary	Investigational Site Number 3480001	Balatonfüred
Hungary	Investigational Site Number 3480002	Budapest
Hungary	Investigational Site Number 3480005	Budapest
Hungary	Investigational Site Number 3480006	Budapest
Hungary	Investigational Site Number 3480007	Budapest
Hungary	Investigational Site Number 3480008	Budapest
Mexico	Investigational Site Number 4840004	Actopan
Mexico	Investigational Site Number 4840001	Guadalajara
Mexico	Investigational Site Number 4840003	Guadalajara
Mexico	Investigational Site Number 4840002	Monterrey
Mexico	Investigational Site Number 4840006	San Juan Del Rio
Russian Federation	Investigational Site Number 6430003	Saratov
Russian Federation	Investigational Site Number 6430001	St-Petersburg
Russian Federation	Investigational Site Number 6430002	St-Petersburg
Russian Federation	Investigational Site Number 6430004	St. Petersburg
Russian Federation	Investigational Site Number 6430005	Voronezh
Spain	Investigational Site Number 7240005	Barcelona
Spain	Investigational Site Number 7240007	Ferrol
Spain	Investigational Site Number 7240001	La Coruña
Spain	Investigational Site Number 7240006	Las Palmas De Gran Canaria
Spain	Investigational Site Number 7240002	Madrid
Spain	Investigational Site Number 7240003	Málaga
Spain	Investigational Site Number 7240004	Málaga
Spain	Investigational Site Number 7240008	Sevilla
United States	Investigational Site Number 8400004	Austin	Texas
United States	Investigational Site Number 8400013	Chicago	Illinois
United States	Investigational Site Number 8400006	Dallas	Texas
United States	Investigational Site Number 8400027	Denver	Colorado
United States	Investigational Site Number 8400005	Fargo	North Dakota
United States	Investigational Site Number 8400014	Flint	Michigan
United States	Investigational Site Number 8400021	Houston	Texas
United States	Investigational Site Number 8400002	Huntington Park	California
United States	Investigational Site Number 8400020	Linden	New Jersey
United States	Investigational Site Number 8400001	Los Angeles	California
United States	Investigational Site Number 8400024	Los Angeles	California
United States	Investigational Site Number 8400025	Miami	Florida
United States	Investigational Site Number 8400018	New Orleans	Louisiana
United States	Investigational Site Number 8400022	New York	New York
United States	Investigational Site Number 8400007	Palm Harbor	Florida
United States	Investigational Site Number 8400012	Port Hueneme	California
United States	Investigational Site Number 8400019	Rockville	Maryland
United States	Investigational Site Number 8400026	San Antonio	Texas
United States	Investigational Site Number 8400028	Sheffield	Alabama
United States	Investigational Site Number 8400017	Sugar Land	Texas
United States	Investigational Site Number 8400003	Troy	Michigan
United States	Investigational Site Number 8400016	Wichita	Kansas
United States	Investigational Site Number 8400023	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Hungary,  Mexico,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in HbA1c to Week 26	Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Missing post-baseline values were imputed by placebo control-based multiple imputation (MI) method under the missing not at random framework.	Baseline, Week 26
Secondary	Mean Change From Baseline in Body Weight to Week 26	Change in body weight was calculated by subtracting baseline value from Week 26 value. Missing post- baseline values were imputed by placebo control-based MI method under the missing not at random framework.	Baseline, Week 26
Secondary	Percentage of Participants Reached HbA1c Target of <6.5% or <7% at Week 26	The analysis included assessment collected during the study, including those obtained after IMP discontinuation or introduction of rescue therapy. Participants with no measurement at Week 26 were treated as non-responders.	Week 26
Secondary	Percentage of Participants Achieving >=5% or >=10% Body Weight Loss at Week 26	The analysis included assessment collected during the study, including those obtained after IMP discontinuation or introduction of rescue therapy. Participants with no measurement at Week 26 were treated as non-responders.	Week 26
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26	Change in FPG was calculated by subtracting baseline value from Week 26 value. Missing post-baseline values were imputed by placebo control-based MI method under the missing not at random framework.	Baseline, Week 26
Secondary	Change From Baseline in Average 7 Point Self-Monitoring Plasma Glucose (SMPG) to Week 26	Change in 7-point SMPG profile from baseline to Week 26 was assessed by summary statistics. 7-point SMPG profiles were measured at the following 7 points at each visit (Baseline, and Week 26): pre-prandial and 2 hours postprandial for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) is defined as 2 hours after the start of the meal.	Baseline, Week 26
Secondary	Percentage of Participants Requiring Rescue Therapy	Rescue medication was introduced in case FPG or HbA1c values were above pre-defined thresholds, and if no reasons were found for insufficient glucose control, and appropriate action failed to decrease FPG / HbA1c under the threshold values (from baseline to Week 8: FPG >270 mg/dL 15.0 mmol/L, from Week 8 to Week 14: FPG >13.3 mmol/L, and from Week 14 to Week 26: FPG >11.1 mmol/L or HbA1c>8%). The choice of rescue therapy was at the Investigator's discretion with the exception of using glucagon-like peptide-1 receptor (GLP-1R) agonists or dipeptidyl peptidase 4 (DPP4) inhibitors.	Baseline up to 26 weeks
Secondary	Change From Baseline in Beta-Cell Function to Week 26	Beta-cell function was assessed by homeostatic model assessment (HOMA)-beta, derived from FPG and fasting plasma insulin (FPI). HOMA-beta was derived from FPG and FPI as (20*FPI [micro units/milliliter]) divided by (FPG [mmol/L] minus 3.5). Change was calculated for HOMA-beta by subtracting the Baseline value from Week 26 value*100.	Baseline, Week 26
Secondary	Change From Baseline in Insulin Resistance to Week 26	Insulin Resistance was assessed by homeostasis model assessment for insulin resistance (HOMA-IR), derived from FPG and FPI. HOMA-IR was derived from FPG and FPI as (FPI [micro units per milliliter] * FPG [mmol/L]) divided by 22.5. Change was calculated for HOMA-beta by subtracting the Baseline value from Week 26 value.	Baseline, Week 26
Secondary	Change From Baseline in Pharmacodynamic Biomarkers to Week 26 - Waist and Hip Circumferences	Waist circumference was measured at the midpoint between the lower margin of the least palpable rib and the top of the iliac crest, using a stretch-resistant tape providing a constant 100 gm tension. Hip circumference was measured around the widest portion of the buttocks, with the tape parallel to the floor. Each measurement was repeated twice; if the measurements were within 1 cm of one another, the average was calculated, and if the difference exceeded 1 cm, the measurements were repeated.	Baseline,Week 26