Efficacy and Safety of Efpeglenatide Versus Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin Alone or in Combination With Sulfonylurea

Study Overview
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Brief Summary
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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 metformin alone or in combination with sulfonylurea (SU). 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.

Detailed Description
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Study duration per participant was approximately 39 weeks including an up to 3-week Screening Period, a 30-week Treatment Period, and a 6-week safety Follow-up Period.

Official Title
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A 30-week, Multicenter, Double-blind, Placebo-controlled, Randomized Study to Evaluate the Efficacy and Safety of Efpeglenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin Alone or in Combination With Sulfonylurea

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Efpeglenatide SAR439977
* Drug: Placebo
* Drug: Background therapy: Metformin alone or in combination with SU


Participation Criteria
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Eligibility Criteria
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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 metformin alone or in combination with SU, for at least 3 months prior to screening. Glycated hemoglobin between 7.0% 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 or history of surgery affecting gastric emptying. 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 millimeters of mercury (mmHg) and/or diastolic blood pressure >100 mmHg at randomization. Severe renal disease as defined by estimated glomerular filtration rate (eGFR) of <30 milliliters per minute per 1.73 square meter. Laboratory findings at the screening visit: Alanine aminotransferase or aspartate aminotransferase >3*upper limit of the normal (ULN) or total bilirubin >1.5*ULN (except in case of documented Gilbert's syndrome); Amylase and/or lipase: >3*ULN laboratory range; Calcitonin >=5.9 picomoles per liter (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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo (matched to Efpeglenatide) subcutaneous (SC) injection once weekly up to Week 30 on top of metformin alone or in combination with SU. | Drug: Placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: Background therapy: Metformin alone or in combination with SU<br>* Pharmaceutical form: tablet Route of administration: oral, administered as per investigator and in accordance with local labeling.<br>|
| Experimental: Efpeglenatide 2 mg<br>Participants received Efpeglenatide 2 milligrams (mg) SC injection once weekly up to Week 30 on top of metformin alone or in combination with SU. | Drug: Efpeglenatide SAR439977<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: Background therapy: Metformin alone or in combination with SU<br>* Pharmaceutical form: tablet Route of administration: oral, administered as per investigator and in accordance with local labeling.<br>|
| Experimental: Efpeglenatide 4 mg<br>Participants received Efpeglenatide 4 mg SC injection once weekly up to Week 30 on top of metformin alone or in combination with SU. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg and was maintained at the 4 mg dose through-out the treatment duration, up to Week 30. | Drug: Efpeglenatide SAR439977<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: Background therapy: Metformin alone or in combination with SU<br>* Pharmaceutical form: tablet Route of administration: oral, administered as per investigator and in accordance with local labeling.<br>|
| Experimental: Efpeglenatide 6 mg<br>Participants received Efpeglenatide 6 mg SC injection once weekly up to Week 30 on top of metformin alone or in combination with SU. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg until Week 3 and later up-titrated to 6 mg and was maintained at the 6 mg dose through-out the treatment duration, up to Week 30. | Drug: Efpeglenatide SAR439977<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: Background therapy: Metformin alone or in combination with SU<br>* Pharmaceutical form: tablet Route of administration: oral, administered as per investigator and in accordance with local labeling.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 30 in HbA1c | This analysis included all Week 30 assessment values available. | Baseline to Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With HbA1c <7.0% | Participants who had no available assessment for HbA1c <7% at Week 30 were considered as non-responders. | Week 30 | 
| Change From Baseline to Week 30 in Fasting Plasma Glucose (FPG) | This analysis included all Week 30 assessment values available. | Baseline to Week 30 | 
| Change From Baseline to Week 30 in Body Weight | This analysis included all Week 30 assessment values available. | Baseline to Week 30 | 
| Number of Participants With At Least One Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL], Severe Hypoglycemia) | Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <54 milligrams per deciliter (mg/dL) (<3.0 mmol/L). Severe hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. | Baseline up to Week 30 | 
| Number of Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL] and Severe Hypoglycemia) Per Participant-Year | Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <54 mg/dL (<3.0 mmol/L). Severe hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. | Baseline up to Week 30 |