Efficacy and Safety of Efpeglenatide Versus Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Diet and Exercise (AMPLITUDE-M)

Hanmi Pharmaceutical

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: efpeglenatide (SAR439977); Drug: placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03353350

EFC14822

2016-001857-42

U1111-1182-1806 (Other Identifier)

Details and patient eligibility

About

Primary Objective:

To demonstrate the superiority of once weekly injection of efpeglenatide in comparison to placebo in glycated hemoglobin (HbA1c) change in participants with T2DM (Type 2 Diabetes Mellitus) inadequately controlled with diet and exercise.

Secondary Objectives:

• To demonstrate the superiority of once-weekly injection of efpeglenatide in comparison to placebo on glycemic control
• To demonstrate the superiority of once-weekly injection of efpeglenatide in comparison to placebo on body weight
• To evaluate the safety of once-weekly injection of efpeglenatide

Full description

Study duration per participant is approximately 65 weeks, including a 3-week screening period, 30 weeks core treatment period, 26 weeks extension treatment period, and 6 weeks safety follow up.

Enrollment: 406 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must be at least 18 years of age at the time of signing the informed consent.
• Participants with T2DM, and treated with diet and exercise.
• Hemoglobin A1c between 7.0% and 10.0% (inclusive) measured by the central laboratory at Screening.

Exclusion criteria

• Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to) gastroparesis, unstable and not controlled gastroesophageal reflux disease within 6 months prior to Screening or history of surgery affecting gastric emptying.
• History of pancreatitis (unless pancreatitis was related to gallstone and cholecystectomy has been performed) and pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, and pancreatectomy.
• Personal or family history of Medullary Thyroidian Cancer (MTC) or genetic conditions that predisposes to MTC (eg multiple endocrine neoplasia syndromes).
• Retinopathy or maculopathy with one of the following treatments, either recent (within 3 months of screening) or planned: intravitreal injections or laser or vitrectomy surgery.
• Body weight change of ≥5 kg within the last 3 months prior to Screening.
• Systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg at Randomization.
• End-stage renal disease as defined by estimated glomerular filtration rate (eGFR , by Modification of Diet in Renal Disease [MDRD]) of <15 mL/min/1.73 m2.
• Laboratory findings at the Screening Visit:
• Alanine aminotransferase (ALT ) or aspartate aminotransferase (AST ) >3 times the upper limit of the normal (ULN ) or total bilirubin >1.5 times the ULN (except in case of documented Gilbert's syndrome).
• Amylase and/or lipase: >3 times the ULN laboratory range.
• Calcitonin ≥5.9 pmol/L (20 pg/mL).
• Gastric surgery or other gastric procedures intended for weight loss within 2 years prior to Screening, or planned during study period.
• History of drug or alcohol abuse within 6 months prior to the time of Screening.
• Pregnant (demonstrated by serum pregnancy test at Screening) or breast-feeding women.
• Women of childbearing potential not willing to use highly effective method(s) of birth control during the study period and for at least 5 weeks after the last dose of study intervention.

The above information is not intended to contain all considerations relevant to a patient'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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406 participants in 4 patient groups, including a placebo group

Efpeglenatide 2mg

Experimental group

Description:

Efpeglenatide low dose (Prefilled syringe) administered once weekly for 56 weeks

Treatment:

Drug: efpeglenatide (SAR439977)

Efpeglenatide 4 mg

Experimental group

Description:

Efpeglenatide middle dose (Prefilled syringe) administered once weekly for 56 weeks (including titration period)

Treatment:

Drug: efpeglenatide (SAR439977)

Efpeglenatide 6 mg

Experimental group

Description:

Efpeglenatide high dose (Prefilled syringe) administered once weekly for 56 weeks (including titration period)

Treatment:

Drug: efpeglenatide (SAR439977)

Placebo

Placebo Comparator group

Description:

Matching placebo (Prefilled syringe) administered once weekly for 56 weeks

Treatment:

Drug: placebo