Efficacy and Safety of Efpeglenatide Versus Dulaglutide in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin (AMPLITUDE-D)

Sanofi

Status and phase: Terminated; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Background therapy Metformin; Drug: Efpeglenatide; Drug: Dulaglutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT03684642

2017-002956-10

EFC14829

U1111-1205-3150 (Other Identifier)

Details and patient eligibility

About

Primary Objective:

To demonstrate the non-inferiority of once weekly injection of efpeglenatide in comparison to once weekly injection of dulaglutide on glycated hemoglobin (HbA1c) change in participants with Type 2 diabetes mellitus (T2DM) inadequately controlled with metformin.

Secondary Objectives:

• To demonstrate the superiority of once weekly injection of efpeglenatide with once weekly injection of dulaglutide on glycemic control.
• To demonstrate the superiority of once weekly injection of efpeglenatide with once weekly injection of dulaglutide on body weight.
• To evaluate the safety of once weekly injection of efpeglenatide and once weekly injection of dulaglutide.

Full description

Study duration per participant was approximately 65 weeks including an up to 3-week Screening Period, a 56-week Treatment Period and a 6-week safety Follow-up Period.

Enrollment: 908 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant must be greater than or equal to (>=) 18 years of age at the time of signing the informed consent.
• Participants with T2DM.
• Diabetes diagnosed at least 1 year before screening.
• Participants on stable dose of at least 1500 milligram per day (mg/day) of metformin, or tolerated maximum dose, or as per country regulation if less, for at least 3 months prior to screening.
• HbA1c between 7.0 percent (%) and 10.0% (inclusive) measured by the central laboratory at screening.

Exclusion criteria

• Retinopathy or maculopathy with one of the following treatments, either recent (within 3 months prior to screening) or planned: intravitreal injections or laser or vitrectomy surgery.
• Clinically relevant history of gastrointestinal (GI) disease associated with prolonged nausea and vomiting, including (but not limited to) gastroparesis, unstable and not controlled gastroesophageal reflux disease requiring medical treatment within 6 months prior to screening or history of surgery affecting gastric emptying.
• History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy had been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy.
• Personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predisposes to MTC (e.g., multiple endocrine neoplasia syndromes).
• Body weight change of greater than or equal to (>=) 5 kilogram within the last 3 months prior to screening.
• Systolic blood pressure greater than (>)180 millimeter of mercury (mmHg) and/or diastolic blood pressure >100 mmHg at randomization.
• Severe renal disease as defined by estimated glomerular filtration rate (eGFR), by Modification of Diet in Renal Disease (MDRD)] of less than (<)30 mL/min/1.73 m^2.
• Laboratory findings at the screening visit:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 * upper limit of normal (ULN) or total bilirubin >1.5 * ULN (except in case of documented Gilbert's syndrome);
• Amylase and/or lipase: >3 * ULN;
• Calcitonin >=5.9 picomoles per liter (pmol/L) (20 picograms per milliliter).
• Gastric surgery or other gastric procedures intended for weight loss within 2 years prior to screening, or planned during study period.
• Pregnant (confirmed by serum pregnancy test at screening) or breast-feeding women.
• Women of childbearing potential (WOCBP) not willing to use highly effective method(s) of birth control or who are unwilling to be tested for pregnancy during the study period and for at least 5 weeks after the last dose of study intervention.

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: None (Open label)

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908 participants in 3 patient groups

Efpeglenatide 4 mg

Experimental group

Description:

Participants received Efpeglenatide subcutaneous (SC) injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 2 mg once weekly and increased every 2 weeks to the maximum of 4 mg once weekly for the treatment duration.

Treatment:

Drug: Efpeglenatide

Drug: Background therapy Metformin

Efpeglenatide 6 mg

Experimental group

Description:

Participants received Efpeglenatide SC injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 2 mg once weekly and increased every 2 weeks to the maximum of 6 mg once weekly for the treatment duration.

Treatment:

Drug: Efpeglenatide

Drug: Background therapy Metformin

Dulaglutide 1.5 mg

Active Comparator group

Description:

Participants received Dulaglutide SC injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 0.75 mg once weekly and increased after 2 weeks to 1.5 mg once weekly for the treatment duration.

Treatment:

Drug: Dulaglutide

Drug: Background therapy Metformin