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

NCT ID: NCT02973321

Last Updated: 2022-03-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

296 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-02

Study Completion Date

2017-12-27

Brief Summary

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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

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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.

Conditions

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Type 2 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Placebo (for SAR425899) subcutaneous (SC) injection once daily (QD) from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Self-administered by SC injection using a solution for injection in cartridge.

Metformin

Intervention Type DRUG

Orally administered at a stable dose , \>=1500 mg daily stable dose or maximal tolerated dose.

SAR425899 0.12 mg

SAR425899 SC injection QD at maintenance dose of 0.12 mg for 25 weeks (Week 2 to Week 26) following 1 week dose increase step (0.06 mg at Week 1).

Group Type EXPERIMENTAL

SAR425899

Intervention Type DRUG

Self-administered by SC injection using a solution for injection in cartridge.

Metformin

Intervention Type DRUG

Orally administered at a stable dose , \>=1500 mg daily stable dose or maximal tolerated dose.

SAR425899 0.16 mg

SAR425899 SC injection QD at maintenance dose of 0.16 mg for 24 weeks (Week 3 to Week 26) following 2 weeks dose increase step (0.06 mg at Week 1 and 0.12 mg at Week 2).

Group Type EXPERIMENTAL

SAR425899

Intervention Type DRUG

Self-administered by SC injection using a solution for injection in cartridge.

Metformin

Intervention Type DRUG

Orally administered at a stable dose , \>=1500 mg daily stable dose or maximal tolerated dose.

SAR425899 0.20 mg

SAR425899 SC injection QD at maintenance dose of 0.20 mg for 23 weeks (Week 4 to Week 26) following 3 weeks dose increase step (0.06 mg at Week 1, 0.12 mg at Week 2 and 0.16 mg at Week 3).

Group Type EXPERIMENTAL

SAR425899

Intervention Type DRUG

Self-administered by SC injection using a solution for injection in cartridge.

Metformin

Intervention Type DRUG

Orally administered at a stable dose , \>=1500 mg daily stable dose or maximal tolerated dose.

Liraglutide

Liraglutide SC injection QD at maintenance dose of 1.8 mg for 24 weeks (Week 3 to Week 26) following 2 weeks dose increase steps (0.6 mg daily at Week 1 and by 1.2 mg daily at Week 2).

Group Type ACTIVE_COMPARATOR

Liraglutide

Intervention Type DRUG

Self-administered by SC injection using a pre-filled pen.

Metformin

Intervention Type DRUG

Orally administered at a stable dose , \>=1500 mg daily stable dose or maximal tolerated dose.

Interventions

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SAR425899

Self-administered by SC injection using a solution for injection in cartridge.

Intervention Type DRUG

Placebo

Self-administered by SC injection using a solution for injection in cartridge.

Intervention Type DRUG

Liraglutide

Self-administered by SC injection using a pre-filled pen.

Intervention Type DRUG

Metformin

Orally administered at a stable dose , \>=1500 mg daily stable dose or maximal tolerated dose.

Intervention Type DRUG

Other Intervention Names

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Victoza

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Investigational Site Number 8400028

Sheffield, Alabama, United States

Site Status

Investigational Site Number 8400002

Huntington Park, California, United States

Site Status

Investigational Site Number 8400024

Los Angeles, California, United States

Site Status

Investigational Site Number 8400001

Los Angeles, California, United States

Site Status

Investigational Site Number 8400012

Port Hueneme, California, United States

Site Status

Investigational Site Number 8400027

Denver, Colorado, United States

Site Status

Investigational Site Number 8400025

Miami, Florida, United States

Site Status

Investigational Site Number 8400007

Palm Harbor, Florida, United States

Site Status

Investigational Site Number 8400013

Chicago, Illinois, United States

Site Status

Investigational Site Number 8400016

Wichita, Kansas, United States

Site Status

Investigational Site Number 8400023

Wichita, Kansas, United States

Site Status

Investigational Site Number 8400018

New Orleans, Louisiana, United States

Site Status

Investigational Site Number 8400019

Rockville, Maryland, United States

Site Status

Investigational Site Number 8400014

Flint, Michigan, United States

Site Status

Investigational Site Number 8400003

Troy, Michigan, United States

Site Status

Investigational Site Number 8400020

Linden, New Jersey, United States

Site Status

Investigational Site Number 8400022

New York, New York, United States

Site Status

Investigational Site Number 8400005

Fargo, North Dakota, United States

Site Status

Investigational Site Number 8400004

Austin, Texas, United States

Site Status

Investigational Site Number 8400006

Dallas, Texas, United States

Site Status

Investigational Site Number 8400021

Houston, Texas, United States

Site Status

Investigational Site Number 8400026

San Antonio, Texas, United States

Site Status

Investigational Site Number 8400017

Sugar Land, Texas, United States

Site Status

Investigational Site Number 1240008

Québec, , Canada

Site Status

Investigational Site Number 1240005

Sainte-Foy, , Canada

Site Status

Investigational Site Number 1240002

Sherbrooke, , Canada

Site Status

Investigational Site Number 1240001

Toronto, , Canada

Site Status

Investigational Site Number 1240003

Vancouver, , Canada

Site Status

Investigational Site Number 2030003

České Budějovice, , Czechia

Site Status

Investigational Site Number 2030001

Krnov, , Czechia

Site Status

Investigational Site Number 2030004

Praha 10 - Uhrineves, , Czechia

Site Status

Investigational Site Number 2030002

Praha 9 - Klanovice, , Czechia

Site Status

Investigational Site Number 2760003

Berlin, , Germany

Site Status

Investigational Site Number 2760001

Dresden, , Germany

Site Status

Investigational Site Number 2760006

Hohenmölsen, , Germany

Site Status

Investigational Site Number 3480001

Balatonfüred, , Hungary

Site Status

Investigational Site Number 3480002

Budapest, , Hungary

Site Status

Investigational Site Number 3480008

Budapest, , Hungary

Site Status

Investigational Site Number 3480005

Budapest, , Hungary

Site Status

Investigational Site Number 3480006

Budapest, , Hungary

Site Status

Investigational Site Number 3480007

Budapest, , Hungary

Site Status

Investigational Site Number 4840004

Actopan, , Mexico

Site Status

Investigational Site Number 4840001

Guadalajara, , Mexico

Site Status

Investigational Site Number 4840003

Guadalajara, , Mexico

Site Status

Investigational Site Number 4840002

Monterrey, , Mexico

Site Status

Investigational Site Number 4840006

San Juan del Río, , Mexico

Site Status

Investigational Site Number 6430002

Saint Petersburg, , Russia

Site Status

Investigational Site Number 6430004

Saint Petersburg, , Russia

Site Status

Investigational Site Number 6430001

Saint Petersburg, , Russia

Site Status

Investigational Site Number 6430003

Saratov, , Russia

Site Status

Investigational Site Number 6430005

Voronezh, , Russia

Site Status

Investigational Site Number 7240001

A Coruña, , Spain

Site Status

Investigational Site Number 7240005

Barcelona, , Spain

Site Status

Investigational Site Number 7240007

Ferrol, , Spain

Site Status

Investigational Site Number 7240006

Las Palmas de Gran Canaria, , Spain

Site Status

Investigational Site Number 7240002

Madrid, , Spain

Site Status

Investigational Site Number 7240003

Málaga, , Spain

Site Status

Investigational Site Number 7240004

Málaga, , Spain

Site Status

Investigational Site Number 7240008

Seville, , Spain

Site Status

Countries

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United States Canada Czechia Germany Hungary Mexico Russia Spain

References

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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.

Reference Type DERIVED
PMID: 33822469 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31679129 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-001328-77

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1179-4786

Identifier Type: OTHER

Identifier Source: secondary_id

DRI13940

Identifier Type: -

Identifier Source: org_study_id

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