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

NCT02973321 | Completed Phase 2 Results DMC

• 3 other identifiers: DRI139402016-001328-77U1111-1179-4786
• Study Type: interventional
• Target: 296
• Locations: 8 countries
• Sites: 59

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Mean Change From Baseline in Body Weight to Week 26

  Baseline, Week 26

• Percentage of Participants Reached HbA1c Target of <6.5% or <7% at Week 26

  Week 26

• Percentage of Participants Achieving >=5% or >=10% Body Weight Loss at Week 26

  Week 26

• Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26

  Baseline, Week 26

• Change From Baseline in Average 7 Point Self-Monitoring Plasma Glucose (SMPG) to Week 26

  Baseline, Week 26

Study Arms (5)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Metformin

SAR425899 0.12 mg

EXPERIMENTAL

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).

Drug: SAR425899; Drug: Metformin

SAR425899 0.16 mg

EXPERIMENTAL

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).

Drug: SAR425899; Drug: Metformin

SAR425899 0.20 mg

EXPERIMENTAL

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).

Drug: SAR425899; Drug: Metformin

Liraglutide

ACTIVE COMPARATOR

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).

Drug: Liraglutide; Drug: Metformin

Interventions

SAR425899 DRUG

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

SAR425899 0.12 mg; SAR425899 0.16 mg; SAR425899 0.20 mg

Placebo DRUG

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

Placebo

Liraglutide DRUG

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

Also known as: Victoza

Liraglutide

Metformin DRUG

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

Liraglutide; Placebo; SAR425899 0.12 mg; SAR425899 0.16 mg; SAR425899 0.20 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (59)

Investigational Site Number 8400028

Sheffield, Alabama, 35660, United States

Location

Investigational Site Number 8400002

Huntington Park, California, 90255, United States

Location

Investigational Site Number 8400024

Los Angeles, California, 90017, United States

Location

Investigational Site Number 8400001

Los Angeles, California, 90057, United States

Location

Investigational Site Number 8400012

Port Hueneme, California, 93041, United States

Location

Investigational Site Number 8400027

Denver, Colorado, 80209, United States

Location

Investigational Site Number 8400025

Miami, Florida, 33166, United States

Location

Investigational Site Number 8400007

Palm Harbor, Florida, 34684, United States

Location

Investigational Site Number 8400013

Chicago, Illinois, 60827, United States

Location

Investigational Site Number 8400016

Wichita, Kansas, 67205, United States

Location

Investigational Site Number 8400023

Wichita, Kansas, 67207, United States

Location

Investigational Site Number 8400018

New Orleans, Louisiana, 70119, United States

Location

Investigational Site Number 8400019

Rockville, Maryland, 20852, United States

Location

Investigational Site Number 8400014

Flint, Michigan, 48532-3447, United States

Location

Investigational Site Number 8400003

Troy, Michigan, 48085, United States

Location

Investigational Site Number 8400020

Linden, New Jersey, 07036, United States

Location

Investigational Site Number 8400022

New York, New York, 10001, United States

Location

Investigational Site Number 8400005

Fargo, North Dakota, 58103, United States

Location

Investigational Site Number 8400004

Austin, Texas, 78731, United States

Location

Investigational Site Number 8400006

Dallas, Texas, 75230, United States

Location

Investigational Site Number 8400021

Houston, Texas, 77079, United States

Location

Investigational Site Number 8400026

San Antonio, Texas, 78229, United States

Location

Investigational Site Number 8400017

Sugar Land, Texas, 77478, United States

Location

Investigational Site Number 1240008

Québec, G1S 2L6, Canada

Location

Investigational Site Number 1240005

Sainte-Foy, G1W4R4, Canada

Location

Investigational Site Number 1240002

Sherbrooke, J1L 0H8, Canada

Location

Investigational Site Number 1240001

Toronto, M4G 3E8, Canada

Location

Investigational Site Number 1240003

Vancouver, V5Y 3W2, Canada

Location

Investigational Site Number 2030003

České Budějovice, 370 01, Czechia

Location

Investigational Site Number 2030001

Krnov, 79401, Czechia

Location

Investigational Site Number 2030004

Praha 10 - Uhrineves, 104 00, Czechia

Location

Investigational Site Number 2030002

Praha 9 - Klanovice, 19014, Czechia

Location

Investigational Site Number 2760003

Berlin, 10115, Germany

Location

Investigational Site Number 2760001

Dresden, 01307, Germany

Location

Investigational Site Number 2760006

Hohenmölsen, 06679, Germany

Location

Investigational Site Number 3480001

Balatonfüred, 8230, Hungary

Location

Investigational Site Number 3480002

Budapest, 1027, Hungary

Location

Investigational Site Number 3480008

Budapest, 1042, Hungary

Location

Investigational Site Number 3480005

Budapest, 1062, Hungary

Location

Investigational Site Number 3480006

Budapest, 1062, Hungary

Location

Investigational Site Number 3480007

Budapest, 1213, Hungary

Location

Investigational Site Number 4840004

Actopan, 42500, Mexico

Location

Investigational Site Number 4840001

Guadalajara, 44600, Mexico

Location

Investigational Site Number 4840003

Guadalajara, 44670, Mexico

Location

Investigational Site Number 4840002

Monterrey, 64460, Mexico

Location

Investigational Site Number 4840006

San Juan del Río, 76800, Mexico

Location

Investigational Site Number 6430002

Saint Petersburg, 190068, Russia

Location

Investigational Site Number 6430004

Saint Petersburg, 194358, Russia

Location

Investigational Site Number 6430001

Saint Petersburg, 195257, Russia

Location

Investigational Site Number 6430003

Saratov, 410030, Russia

Location

Investigational Site Number 6430005

Voronezh, 394018, Russia

Location

Investigational Site Number 7240001

A Coruña, 15006, Spain

Location

Investigational Site Number 7240005

Barcelona, 08035, Spain

Location

Investigational Site Number 7240007

Ferrol, 15405, Spain

Location

Investigational Site Number 7240006

Las Palmas de Gran Canaria, 35016, Spain

Location

Investigational Site Number 7240002

Madrid, 28040, Spain

Location

Investigational Site Number 7240003

Málaga, 29010, Spain

Location

Investigational Site Number 7240004

Málaga, 29010, Spain

Location

Investigational Site Number 7240008

Seville, 41071, Spain

Location

Related Publications (2)

• 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.

  PMID: 33822469 DERIVED

• 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.

  PMID: 31679129 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

SAR425899; Liraglutide; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2016
• First Posted: November 25, 2016
• Study Start: December 2, 2016
• Primary Completion: December 27, 2017
• Study Completion: December 27, 2017
• Last Updated: March 24, 2022
• Results First Posted: February 9, 2021

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

CA (5); HU (6); ME (5); US (23); CZ (4); RU (5); ES (8); DE (3)