Efficacy and Safety of Efpeglenatide Versus Dulaglutide in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin

Type 2 Diabetes Mellitus Clinical Trial

— AMPLITUDE-D  

Official title:

A 56-week, Multicenter, Open-label, Active-controlled, Randomized Study to Evaluate the Efficacy and Safety of Efpeglenatide Once Weekly Compared to Dulaglutide Once Weekly in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03684642
• Other study ID #: EFC14829
• Secondary ID: 2017-002956-10U1
• Status: Terminated
• Phase: Phase 3
• Start date: September 26, 2018
• Est. completion date: November 17, 2020

Study information

• Verified date: October 2021
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 908
• Est. completion date: November 17, 2020
• Est. primary completion date: October 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Efpeglenatide
Pharmaceutical form: solution for injection; Route of administration: SC
• Dulaglutide
Pharmaceutical form: solution for injection; Route of administration: SC
• Background therapy Metformin
Pharmaceutical form: tablet; Route of administration: oral; Dose to be kept stable throughout the study.

Locations

Country	Name	City	State
Hungary	Investigational Site Number 3480004	Budapest
Hungary	Investigational Site Number 3480003	Debrecen
Hungary	Investigational Site Number 3480001	Gyula
Hungary	Investigational Site Number 3480005	Hatvan
Hungary	Investigational Site Number 3480002	Nyíregyháza
Poland	Investigational Site Number 6160008	Gdansk
Poland	Investigational Site Number 6160004	Gdynia
Poland	Investigational Site Number 6160010	Katowice
Poland	Investigational Site Number 6160009	Poznan
Poland	Investigational Site Number 6160003	Warszawa
Poland	Investigational Site Number 6160001	Wroclaw
Ukraine	Investigational Site Number 8040001	Kyiv
Ukraine	Investigational Site Number 8040002	Kyiv
Ukraine	Investigational Site Number 8040003	Kyiv
Ukraine	Investigational Site Number 8040004	Vinnytsia
United States	Investigational Site Number 8400038	Birmingham	Alabama
United States	Investigational Site Number 8400061	Boston	Massachusetts
United States	Investigational Site Number 8400001	Bridgeton	New Jersey
United States	Investigational Site Number 8400028	Burlington	North Carolina
United States	Investigational Site Number 8400035	Chandler	Arizona
United States	Investigational Site Number 8400030	Dallas	Texas
United States	Investigational Site Number 8400005	Glendale	Arizona
United States	Investigational Site Number 8400014	Goose Creek	South Carolina
United States	Investigational Site Number 8400057	Huntington Park	California
United States	Investigational Site Number 8400025	Lawrenceville	Georgia
United States	Investigational Site Number 8400037	Layton	Utah
United States	Investigational Site Number 8400044	Lexington	Kentucky
United States	Investigational Site Number 8400009	Los Angeles	California
United States	Investigational Site Number 8400049	Manassas	Virginia
United States	Investigational Site Number 8400013	Maumee	Ohio
United States	Investigational Site Number 8400060	Meridian	Idaho
United States	Investigational Site Number 8400036	Morehead City	North Carolina
United States	Investigational Site Number 8400039	New Windsor	New York
United States	Investigational Site Number 8400055	Orlando	Florida
United States	Investigational Site Number 8400041	Pembroke Pines	Florida
United States	Investigational Site Number 8400054	Peoria	Arizona
United States	Investigational Site Number 8400020	San Antonio	Texas
United States	Investigational Site Number 8400043	San Antonio	Texas
United States	Investigational Site Number 8400053	San Antonio	Texas
United States	Investigational Site Number 8400007	San Diego	California
United States	Investigational Site Number 8400059	Skokie	Illinois
United States	Investigational Site Number 8400045	Spring Valley	California
United States	Investigational Site Number 8400040	Tustin	California
United States	Investigational Site Number 8400026	Van Nuys	California
United States	Investigational Site Number 8400050	Waterbury	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Hanmi Pharmaceutical Company Limited

Countries where clinical trial is conducted

United States,  Hungary,  Poland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 56 in HbA1c	Adjusted Least square (LS) means and Standard errors (SE) were obtained from analysis of covariance (ANCOVA) model to account for missing data. Missing values were imputed by baseline observation carried forward (BOCF)-like multiple imputation method.	Baseline to Week 56
Secondary	Change From Baseline to Week 56 in Body Weight	Adjusted LS means and SE were obtained from ANCOVA model to account for missing data. Missing values were imputed by BOCF-like multiple imputation method.	Baseline to Week 56
Secondary	Number of Participants With HbA1c < 7.0 %	Participants who had no available assessment for HbA1c at Week 56 were considered as non-responders.	Week 56
Secondary	Change From Baseline to Week 56 in Fasting Plasma Glucose (FPG)	Adjusted LS means and SE were obtained from ANCOVA model to account for missing data. Missing values were imputed by BOCF-like multiple imputation method.	Baseline to Week 56
Secondary	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 56
Secondary	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 56