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)

Type 2 Diabetes Mellitus Clinical Trial

— AMPLITUDE-L  

Official title:

A 56-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 Basal Insulin Alone or in Combination With Oral Antidiabetic Drug(s)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03713684
• Other study ID #: EFC14893
• Secondary ID: U1111-1189-5009
• Status: Terminated
• Phase: Phase 3
• Start date: November 9, 2018
• Est. completion date: January 4, 2021

Study information

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

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 370
• Est. completion date: January 4, 2021
• Est. primary completion date: November 20, 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 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Efpeglenatide SAR439977
Pharmaceutical form: solution for injection Route of administration: subcutaneous
• Placebo
Pharmaceutical form: solution for injection Route of administration: subcutaneous
• Background therapy
Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.

Locations

Country	Name	City	State
China	Investigational Site Number 1560005	Baotou
China	Investigational Site Number 1560017	Beijing
China	Investigational Site Number 1560006	Changsha
China	Investigational Site Number 1560001	Chengdu
China	Investigational Site Number 1560004	Shanghai
China	Investigational Site Number 1560012	Shanghai
China	Investigational Site Number 1560013	Shanghai
China	Investigational Site Number 1560036	Shanghai
China	Investigational Site Number 1560003	Zhengzhou
Korea, Republic of	Investigational Site Number 4100009	Busan
Korea, Republic of	Investigational Site Number 4100001	Daejeon
Korea, Republic of	Investigational Site Number 4100010	Gwangju
Korea, Republic of	Investigational Site Number 4100016	Gwangju
Korea, Republic of	Investigational Site Number 4100013	Gyeonggi-do
Korea, Republic of	Investigational Site Number 4100015	Incheon
Korea, Republic of	Investigational Site Number 4100014	Jeonju
Korea, Republic of	Investigational Site Number 4100007	Seongnam-Si
Korea, Republic of	Investigational Site Number 4100002	Seoul
Korea, Republic of	Investigational Site Number 4100003	Seoul
Korea, Republic of	Investigational Site Number 4100004	Seoul
Korea, Republic of	Investigational Site Number 4100005	Seoul
Korea, Republic of	Investigational Site Number 4100006	Seoul
Korea, Republic of	Investigational Site Number 4100008	Seoul
Korea, Republic of	Investigational Site Number 4100011	Seoul
Korea, Republic of	Investigational Site Number 4100012	Suwon
United States	Investigational Site Number 8400038	Birmingham	Alabama
United States	Investigational Site Number 8400001	Bridgeton	New Jersey
United States	Investigational Site Number 8400035	Chandler	Arizona
United States	Investigational Site Number 8400030	Dallas	Texas
United States	Investigational Site Number 8400063	Dallas	Texas
United States	Investigational Site Number 8400005	Glendale	Arizona
United States	Investigational Site Number 8400057	Huntington Park	California
United States	Investigational Site Number 8400058	La Jolla	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 8400013	Maumee	Ohio
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 8400043	San Antonio	Texas
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 8400052	West Des Moines	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Hanmi Pharmaceutical Company Limited

Countries where clinical trial is conducted

United States,  China,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 30 in HbA1c		Baseline to Week 30
Secondary	Number of Participants With HbA1c <7.0% at Week 30	Participants who had no available assessment for HbA1c at Week 30 were considered as non-responders.	Week 30
Secondary	Change From Baseline to Week 56 in HbA1c	This analysis included Week 56 assessment performed per protocol as well as premature end of treatment/study visit recorded as Week 56 due to early termination.	Baseline to Week 56
Secondary	Change From Baseline to Week 30 in Fasting Plasma Glucose (FPG)		Baseline to Week 30
Secondary	Change From Baseline to Week 30 and Week 56 in Body Weight	This analysis included Week 56 assessment performed per protocol as well as premature end of treatment/study visit recorded as Week 56 due to early termination.	Baseline to Week 30 and Week 56
Secondary	Number of Participants With At Least One Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL], and Severe Hypoglycemia)	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
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