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Efficacy and Safety of Efpeglenatide Versus Dulaglutide in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin (AMPLITUDE-D)

Primary Purpose

Type 2 Diabetes Mellitus

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Efpeglenatide
Dulaglutide
Background therapy Metformin
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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 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.

Sites / Locations

  • Investigational Site Number 8400038
  • Investigational Site Number 8400035
  • Investigational Site Number 8400005
  • Investigational Site Number 8400054
  • Investigational Site Number 8400057
  • Investigational Site Number 8400009
  • Investigational Site Number 8400007
  • Investigational Site Number 8400045
  • Investigational Site Number 8400040
  • Investigational Site Number 8400026
  • Investigational Site Number 8400050
  • Investigational Site Number 8400055
  • Investigational Site Number 8400041
  • Investigational Site Number 8400025
  • Investigational Site Number 8400060
  • Investigational Site Number 8400059
  • Investigational Site Number 8400044
  • Investigational Site Number 8400061
  • Investigational Site Number 8400001
  • Investigational Site Number 8400039
  • Investigational Site Number 8400028
  • Investigational Site Number 8400036
  • Investigational Site Number 8400013
  • Investigational Site Number 8400014
  • Investigational Site Number 8400030
  • Investigational Site Number 8400020
  • Investigational Site Number 8400043
  • Investigational Site Number 8400053
  • Investigational Site Number 8400037
  • Investigational Site Number 8400049
  • Investigational Site Number 3480004
  • Investigational Site Number 3480003
  • Investigational Site Number 3480001
  • Investigational Site Number 3480005
  • Investigational Site Number 3480002
  • Investigational Site Number 6160008
  • Investigational Site Number 6160004
  • Investigational Site Number 6160010
  • Investigational Site Number 6160009
  • Investigational Site Number 6160003
  • Investigational Site Number 6160001
  • Investigational Site Number 8040003
  • Investigational Site Number 8040001
  • Investigational Site Number 8040002
  • Investigational Site Number 8040004

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Efpeglenatide 4 mg

Efpeglenatide 6 mg

Dulaglutide 1.5 mg

Arm Description

Participants received Efpeglenatide subcutaneous (SC) injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 2 mg once weekly and increased every 2 weeks to the maximum of 4 mg once weekly for the treatment duration.

Participants received Efpeglenatide SC injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 2 mg once weekly and increased every 2 weeks to the maximum of 6 mg once weekly for the treatment duration.

Participants received Dulaglutide SC injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 0.75 mg once weekly and increased after 2 weeks to 1.5 mg once weekly for the treatment duration.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Number of Participants With HbA1c < 7.0 %
Participants who had no available assessment for HbA1c at Week 56 were considered as non-responders.
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.
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.
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.

Full Information

First Posted
September 24, 2018
Last Updated
October 28, 2021
Sponsor
Sanofi
Collaborators
Hanmi Pharmaceutical Company Limited
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1. Study Identification

Unique Protocol Identification Number
NCT03684642
Brief Title
Efficacy and Safety of Efpeglenatide Versus Dulaglutide in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision to cancel TRIAL, not related to safety concern.
Study Start Date
September 26, 2018 (Actual)
Primary Completion Date
October 13, 2020 (Actual)
Study Completion Date
November 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Hanmi Pharmaceutical Company Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
The study was open-label for the tested versus comparator drug and double blind for the doses.
Allocation
Randomized
Enrollment
908 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Efpeglenatide 4 mg
Arm Type
Experimental
Arm Description
Participants received Efpeglenatide subcutaneous (SC) injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 2 mg once weekly and increased every 2 weeks to the maximum of 4 mg once weekly for the treatment duration.
Arm Title
Efpeglenatide 6 mg
Arm Type
Experimental
Arm Description
Participants received Efpeglenatide SC injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 2 mg once weekly and increased every 2 weeks to the maximum of 6 mg once weekly for the treatment duration.
Arm Title
Dulaglutide 1.5 mg
Arm Type
Active Comparator
Arm Description
Participants received Dulaglutide SC injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 0.75 mg once weekly and increased after 2 weeks to 1.5 mg once weekly for the treatment duration.
Intervention Type
Drug
Intervention Name(s)
Efpeglenatide
Other Intervention Name(s)
SAR439977
Intervention Description
Pharmaceutical form: solution for injection; Route of administration: SC
Intervention Type
Drug
Intervention Name(s)
Dulaglutide
Other Intervention Name(s)
Trulicity™
Intervention Description
Pharmaceutical form: solution for injection; Route of administration: SC
Intervention Type
Drug
Intervention Name(s)
Background therapy Metformin
Intervention Description
Pharmaceutical form: tablet; Route of administration: oral; Dose to be kept stable throughout the study.
Primary Outcome Measure Information:
Title
Change From Baseline to Week 56 in HbA1c
Description
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.
Time Frame
Baseline to Week 56
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 56 in Body Weight
Description
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.
Time Frame
Baseline to Week 56
Title
Number of Participants With HbA1c < 7.0 %
Description
Participants who had no available assessment for HbA1c at Week 56 were considered as non-responders.
Time Frame
Week 56
Title
Change From Baseline to Week 56 in Fasting Plasma Glucose (FPG)
Description
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.
Time Frame
Baseline to Week 56
Title
Number of Participants With At Least One Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL], Severe Hypoglycemia)
Description
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.
Time Frame
Baseline up to Week 56
Title
Number of Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL] and Severe Hypoglycemia) Per Participant-Year
Description
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.
Time Frame
Baseline up to Week 56

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 8400038
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35211
Country
United States
Facility Name
Investigational Site Number 8400035
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Facility Name
Investigational Site Number 8400005
City
Glendale
State/Province
Arizona
ZIP/Postal Code
85306
Country
United States
Facility Name
Investigational Site Number 8400054
City
Peoria
State/Province
Arizona
ZIP/Postal Code
85381
Country
United States
Facility Name
Investigational Site Number 8400057
City
Huntington Park
State/Province
California
ZIP/Postal Code
90255
Country
United States
Facility Name
Investigational Site Number 8400009
City
Los Angeles
State/Province
California
ZIP/Postal Code
90057
Country
United States
Facility Name
Investigational Site Number 8400007
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
Facility Name
Investigational Site Number 8400045
City
Spring Valley
State/Province
California
ZIP/Postal Code
91978
Country
United States
Facility Name
Investigational Site Number 8400040
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Facility Name
Investigational Site Number 8400026
City
Van Nuys
State/Province
California
ZIP/Postal Code
91405
Country
United States
Facility Name
Investigational Site Number 8400050
City
Waterbury
State/Province
Connecticut
ZIP/Postal Code
06708
Country
United States
Facility Name
Investigational Site Number 8400055
City
Orlando
State/Province
Florida
ZIP/Postal Code
32825
Country
United States
Facility Name
Investigational Site Number 8400041
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33026
Country
United States
Facility Name
Investigational Site Number 8400025
City
Lawrenceville
State/Province
Georgia
ZIP/Postal Code
30044
Country
United States
Facility Name
Investigational Site Number 8400060
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
Facility Name
Investigational Site Number 8400059
City
Skokie
State/Province
Illinois
ZIP/Postal Code
60077
Country
United States
Facility Name
Investigational Site Number 8400044
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40503
Country
United States
Facility Name
Investigational Site Number 8400061
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Investigational Site Number 8400001
City
Bridgeton
State/Province
New Jersey
ZIP/Postal Code
08302
Country
United States
Facility Name
Investigational Site Number 8400039
City
New Windsor
State/Province
New York
ZIP/Postal Code
12553
Country
United States
Facility Name
Investigational Site Number 8400028
City
Burlington
State/Province
North Carolina
ZIP/Postal Code
27215
Country
United States
Facility Name
Investigational Site Number 8400036
City
Morehead City
State/Province
North Carolina
ZIP/Postal Code
28557
Country
United States
Facility Name
Investigational Site Number 8400013
City
Maumee
State/Province
Ohio
ZIP/Postal Code
43537
Country
United States
Facility Name
Investigational Site Number 8400014
City
Goose Creek
State/Province
South Carolina
ZIP/Postal Code
29445
Country
United States
Facility Name
Investigational Site Number 8400030
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Investigational Site Number 8400020
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78218
Country
United States
Facility Name
Investigational Site Number 8400043
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Investigational Site Number 8400053
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78258
Country
United States
Facility Name
Investigational Site Number 8400037
City
Layton
State/Province
Utah
ZIP/Postal Code
84041
Country
United States
Facility Name
Investigational Site Number 8400049
City
Manassas
State/Province
Virginia
ZIP/Postal Code
20110
Country
United States
Facility Name
Investigational Site Number 3480004
City
Budapest
ZIP/Postal Code
1036
Country
Hungary
Facility Name
Investigational Site Number 3480003
City
Debrecen
ZIP/Postal Code
4025
Country
Hungary
Facility Name
Investigational Site Number 3480001
City
Gyula
ZIP/Postal Code
5700
Country
Hungary
Facility Name
Investigational Site Number 3480005
City
Hatvan
ZIP/Postal Code
3000
Country
Hungary
Facility Name
Investigational Site Number 3480002
City
Nyíregyháza
ZIP/Postal Code
4400
Country
Hungary
Facility Name
Investigational Site Number 6160008
City
Gdansk
ZIP/Postal Code
80-382
Country
Poland
Facility Name
Investigational Site Number 6160004
City
Gdynia
ZIP/Postal Code
81-537
Country
Poland
Facility Name
Investigational Site Number 6160010
City
Katowice
ZIP/Postal Code
40-040
Country
Poland
Facility Name
Investigational Site Number 6160009
City
Poznan
ZIP/Postal Code
60-702
Country
Poland
Facility Name
Investigational Site Number 6160003
City
Warszawa
ZIP/Postal Code
01-192
Country
Poland
Facility Name
Investigational Site Number 6160001
City
Wroclaw
ZIP/Postal Code
50-381
Country
Poland
Facility Name
Investigational Site Number 8040003
City
Kyiv
ZIP/Postal Code
02002
Country
Ukraine
Facility Name
Investigational Site Number 8040001
City
Kyiv
ZIP/Postal Code
03037
Country
Ukraine
Facility Name
Investigational Site Number 8040002
City
Kyiv
ZIP/Postal Code
03049
Country
Ukraine
Facility Name
Investigational Site Number 8040004
City
Vinnytsia
ZIP/Postal Code
21050
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
No plan to share individual participant data (IPD) by SANOFI: Product rights transferred to Hanmi Pharmaceutical.

Learn more about this trial

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

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