Clinical trial NCT02973321: A Study to Assess the Safety and Efficacy of SAR425899 in Patients With Type 2 Diabetes Mellitus
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-11-25
Enrollment: 296
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in HbA1c to Week 26
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Mean Change From Baseline in Body Weight to Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Participants Reached HbA1c Target of <6.5% or <7% at Week 26
timeFrame: Week 26
measure: Percentage of Participants Achieving >=5% or >=10% Body Weight Loss at Week 26
timeFrame: Week 26
measure: Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Average 7 Point Self-Monitoring Plasma Glucose (SMPG) to Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Participants Requiring Rescue Therapy
timeFrame: Baseline up to 26 weeks
measure: Change From Baseline in Beta-Cell Function to Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Insulin Resistance to Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Pharmacodynamic Biomarkers to Week 26 - Waist and Hip Circumferences
timeFrame: Baseline,Week 26
Other outcomes:
Locations:
city: Sheffield
country: United States
facility: Investigational Site Number 8400028
state: Alabama
city: Huntington Park
country: United States
facility: Investigational Site Number 8400002
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 8400024
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 8400001
state: California
city: Port Hueneme
country: United States
facility: Investigational Site Number 8400012
state: California
city: Denver
country: United States
facility: Investigational Site Number 8400027
state: Colorado
city: Miami
country: United States
facility: Investigational Site Number 8400025
state: Florida
city: Palm Harbor
country: United States
facility: Investigational Site Number 8400007
state: Florida
city: Chicago
country: United States
facility: Investigational Site Number 8400013
state: Illinois
city: Wichita
country: United States
facility: Investigational Site Number 8400016
state: Kansas
city: Wichita
country: United States
facility: Investigational Site Number 8400023
state: Kansas
city: New Orleans
country: United States
facility: Investigational Site Number 8400018
state: Louisiana
city: Rockville
country: United States
facility: Investigational Site Number 8400019
state: Maryland
city: Flint
country: United States
facility: Investigational Site Number 8400014
state: Michigan
city: Troy
country: United States
facility: Investigational Site Number 8400003
state: Michigan
city: Linden
country: United States
facility: Investigational Site Number 8400020
state: New Jersey
city: New York
country: United States
facility: Investigational Site Number 8400022
state: New York
city: Fargo
country: United States
facility: Investigational Site Number 8400005
state: North Dakota
city: Austin
country: United States
facility: Investigational Site Number 8400004
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8400006
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8400021
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8400026
state: Texas
city: Sugar Land
country: United States
facility: Investigational Site Number 8400017
state: Texas
city: Quebec
country: Canada
facility: Investigational Site Number 1240008
city: Sainte-Foy
country: Canada
facility: Investigational Site Number 1240005
city: Sherbrooke
country: Canada
facility: Investigational Site Number 1240002
city: Toronto
country: Canada
facility: Investigational Site Number 1240001
city: Vancouver
country: Canada
facility: Investigational Site Number 1240003
city: Ceske Budejovice
country: Czechia
facility: Investigational Site Number 2030003
city: Krnov
country: Czechia
facility: Investigational Site Number 2030001
city: Praha 10 - Uhrineves
country: Czechia
facility: Investigational Site Number 2030004
city: Praha 9 - Klanovice
country: Czechia
facility: Investigational Site Number 2030002
city: Berlin
country: Germany
facility: Investigational Site Number 2760003
city: Dresden
country: Germany
facility: Investigational Site Number 2760001
city: Hohenmölsen
country: Germany
facility: Investigational Site Number 2760006
city: Balatonfüred
country: Hungary
facility: Investigational Site Number 3480001
city: Budapest
country: Hungary
facility: Investigational Site Number 3480002
city: Budapest
country: Hungary
facility: Investigational Site Number 3480008
city: Budapest
country: Hungary
facility: Investigational Site Number 3480005
city: Budapest
country: Hungary
facility: Investigational Site Number 3480006
city: Budapest
country: Hungary
facility: Investigational Site Number 3480007
city: Actopan
country: Mexico
facility: Investigational Site Number 4840004
city: Guadalajara
country: Mexico
facility: Investigational Site Number 4840001
city: Guadalajara
country: Mexico
facility: Investigational Site Number 4840003
city: Monterrey
country: Mexico
facility: Investigational Site Number 4840002
city: San Juan Del Rio
country: Mexico
facility: Investigational Site Number 4840006
city: Saratov
country: Russian Federation
facility: Investigational Site Number 6430003
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430002
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430001
city: St. Petersburg
country: Russian Federation
facility: Investigational Site Number 6430004
city: Voronezh
country: Russian Federation
facility: Investigational Site Number 6430005
city: Barcelona
country: Spain
facility: Investigational Site Number 7240005
city: Ferrol
country: Spain
facility: Investigational Site Number 7240007
city: La Coruña
country: Spain
facility: Investigational Site Number 7240001
city: Las Palmas De Gran Canaria
country: Spain
facility: Investigational Site Number 7240006
city: Madrid
country: Spain
facility: Investigational Site Number 7240002
city: Málaga
country: Spain
facility: Investigational Site Number 7240003
city: Málaga
country: Spain
facility: Investigational Site Number 7240004
city: Sevilla
country: Spain
facility: Investigational Site Number 7240008
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Schiavon M, Visentin R, Gobel B, Riz M, Cobelli C, Klabunde T, Dalla Man C. Improved postprandial glucose metabolism in type 2 diabetes by the dual glucagon-like peptide-1/glucagon receptor agonist SAR425899 in comparison with liraglutide. Diabetes Obes Metab. 2021 Aug;23(8):1795-1805. doi: 10.1111/dom.14394. Epub 2021 May 5.
citation: Gater A, Reaney M, Findley A, Brun-Strang C, Burrows K, Nguyen-Pascal ML, Roborel de Climens A. Development and First Use of the Patient's Qualitative Assessment of Treatment (PQAT) Questionnaire in Type 2 Diabetes Mellitus to Explore Individualised Benefit-Harm of Drugs Received During Clinical Studies. Drug Saf. 2020 Feb;43(2):119-134. doi: 10.1007/s40264-019-00877-4.