Efficacy and Safety of Efpeglenatide Versus Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Basal Insulin Alone or in Combination With Oral Antidiabetic Drug(s) (AMPLITUDE-L)

Sanofi

Status and phase: Terminated; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Background therapy; Drug: Efpeglenatide SAR439977; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03713684

U1111-1189-5009 (Other Identifier)

EFC14893

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 type 2 diabetes mellitus (T2DM) inadequately controlled with basal insulin alone or in combination with oral antidiabetic drugs (OADs).

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 was approximately 64 weeks including an up to 2-week Screening Period, a 30-week Core Treatment Period, a 26-week Safety Extension Period, and a 6-week safety Follow-up Period.

Enrollment: 370 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 basal insulin regimen alone or in combination with OADs for at least 6 months prior to screening.
• HbA1c between 7.0 percent (%) and 10.0% (inclusive) measured by the central laboratory at screening.

Exclusion criteria

• History of severe hypoglycemia requiring emergency room admission or hospitalization within 3 months prior to screening.

• 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 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.

• History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has 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 predispose to MTC (e.g., multiple endocrine neoplasia syndromes).

• Body weight change of >=5 kilograms within the last 3 months prior to screening.

• Systolic blood pressure greater than (>)180 millimetres of mercury (mmHg) and/or diastolic blood pressure >100 mmHg at randomization.

• End-stage renal disease as defined by estimated glomerular filtration rate (by Modification of Diet in Renal Disease) of less than 15 mL/min/1.73 m^2.

• Laboratory findings at the screening Visit:

  • Alanine aminotransferase or aspartate aminotransferase >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 [pg/mL]).

• 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 not willing to use highly effective method(s) of birth control or who were 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: Quadruple Blind

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370 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received placebo (matched to efpeglenatide) subcutaneous (SC) injection once weekly up to Week 56 on top of basal insulin alone or in combination with oral antidiabetic drugs (OADs).

Treatment:

Drug: Placebo

Drug: Background therapy

Efpeglenatide 2 mg

Experimental group

Description:

Participants received Efpeglenatide 2 milligrams (mg) SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs.

Treatment:

Drug: Background therapy

Drug: Efpeglenatide SAR439977

Efpeglenatide 4 mg

Experimental group

Description:

Participants received Efpeglenatide 4 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg and maintained at the 4 mg dose through-out the treatment duration up to Week 56.

Treatment:

Drug: Background therapy

Drug: Efpeglenatide SAR439977

Efpeglenatide 6 mg

Experimental group

Description:

Participants received Efpeglenatide 6 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg until Week 4 and later up-titrated to 6 mg and maintained at the 6 mg dose through-out the treatment duration up to Week 56.

Treatment:

Drug: Background therapy

Drug: Efpeglenatide SAR439977