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

Sanofi

Status and phase: Completed; Phase 2

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: SAR425899; Drug: Placebo; Drug: Metformin; Drug: Liraglutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT02973321

2016-001328-77 (EudraCT Number)

U1111-1179-4786 (Other Identifier)

DRI13940

Details and patient eligibility

About

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.

Full 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.

Enrollment: 296 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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296 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Metformin

Drug: Placebo

SAR425899 0.12 mg

Experimental group

Description:

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).

Treatment:

Drug: Metformin

Drug: SAR425899

SAR425899 0.16 mg

Experimental group

Description:

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).

Treatment:

Drug: Metformin

Drug: SAR425899

SAR425899 0.20 mg

Experimental group

Description:

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).

Treatment:

Drug: Metformin

Drug: SAR425899

Liraglutide

Active Comparator group

Description:

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).

Treatment:

Drug: Liraglutide

Drug: Metformin