Effect of Efpeglenatide on Cardiovascular Outcomes (AMPLITUDE-O)

Sanofi

Status and phase: Terminated; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo; Drug: Efpeglenatide (SAR439977)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03496298

2017-002954-35 (EudraCT Number)

U1111-1186-2533 (Other Identifier)

EFC14828

Details and patient eligibility

About

Primary Objective:

To demonstrate that efpeglenatide 4 and 6 mg was noninferior to placebo on 3-point major adverse cardiac events (MACE) in Type 2 diabetes mellitus (T2DM) participants at high cardiovascular (CV) risk.

Secondary Objectives:

To demonstrate that efpeglenatide 4 and 6 mg was superior to placebo in T2DM participants with high CV risk on the following parameters:

• 3-point MACE.
• Expanded CV outcome.
• Composite outcome of new or worsening nephropathy.

To assess the safety and tolerability of efpeglenatide 4 and 6 mg, both added to standard of care in T2DM participants at high CV risk.

Full description

The study duration per participant was up to approximately 36 months.

Enrollment: 4,076 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• T2DM with glycosylated hemoglobin (HbA1c) greater than (>) 7 percentage.
• Age 18 years or older who met at least one of the cardiovascular disease criteria or age 50 years (male), 55 years (female) or older with glomerular filtration rate greater than or equal to 25 and less than 60 milliliters per minute and at least had one cardiovascular risk factor.
• Female participants agreed to follow contraceptive guidance.
• Signed written informed consent.

Exclusion criteria

• Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting.
• History of chronic pancreatitis or acute idiopathic pancreatitis or diagnosis of any type of acute pancreatitis within 3 months prior to screening.
• Personal or family history of medullary thyroid cancer.
• Hypertension (with a systolic blood pressure >180 millimeters of Mercury [mmHg] and/or diastolic blood pressure >100 mmHg).
• Hospitalization for hypertensive emergency within 3 months prior to randomization.
• Planned coronary procedure or surgery after randomization.
• No documented ophthalmologic exam with fundoscopy within 6 months prior to randomization.
• Retinopathy or maculopathy with treatment, either recent (3 months prior to randomization) or planned during the study.
• Treated with any glucagon-like peptide-1 receptor agonist product alone (eg, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide) or in combination within 3 months prior to screening.
• Use of any Dipeptidyl peptidase 4 inhibitor within 3 months prior to screening.
• Antihyperglycemic treatment had not been stable within 3 months prior to screening.

The above information was 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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4,076 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received placebo (matched to Efpeglenatide) as subcutaneous (SC) injection once weekly up to end of treatment.

Treatment:

Drug: Placebo

Efpeglenatide 4 mg

Experimental group

Description:

Participants received Efpeglenatide as SC injection 2 milligrams (mg) per week for 4 weeks then 4 mg per week up to end of treatment.

Treatment:

Drug: Efpeglenatide (SAR439977)

Efpeglenatide 6 mg

Experimental group

Description:

Participants received Efpeglenatide as SC injection 2 mg per week for 4 weeks, then 4 mg per week for 4 weeks and then 6 mg per week up to end of treatment.

Treatment:

Drug: Efpeglenatide (SAR439977)