Back to resultsEfficacy and Safety of Efpeglenatide Versus Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin Alone or in Combination With Sulfonylurea (AMPLITUDE-S)
Primary Purpose
Type 2 Diabetes Mellitus
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Efpeglenatide SAR439977
Placebo
Background therapy: Metformin alone or in combination with SU
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus
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 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.
Sites / Locations
- Investigational Site Number 8400038
- Investigational Site Number 8400035
- Investigational Site Number 8400005
- Investigational Site Number 8400042
- Investigational Site Number 8400051
- Investigational Site Number 8400056
- Investigational Site Number 8400057
- Investigational Site Number 8400009
- Investigational Site Number 8400045
- Investigational Site Number 8400040
- Investigational Site Number 8400047
- Investigational Site Number 8400046
- Investigational Site Number 8400041
- Investigational Site Number 8400025
- Investigational Site Number 8400044
- Investigational Site Number 8400001
- Investigational Site Number 8400039
- Investigational Site Number 8400036
- Investigational Site Number 8400013
- Investigational Site Number 8400048
- Investigational Site Number 8400030
- Investigational Site Number 8400043
- Investigational Site Number 8400037
- Investigational Site Number 1560005
- Investigational Site Number 1560042
- Investigational Site Number 1560053
- Investigational Site Number 1560051
- Investigational Site Number 1560011
- Investigational Site Number 1560025
- Investigational Site Number 1560055
- Investigational Site Number 1560024
- Investigational Site Number 1560020
- Investigational Site Number 1560031
- Investigational Site Number 1560030
- Investigational Site Number 1560012
- Investigational Site Number 1560013
- Investigational Site Number 1560004
- Investigational Site Number 1560022
- Investigational Site Number 1560041
- Investigational Site Number 1560010
- Investigational Site Number 1560052
- Investigational Site Number 1560034
- Investigational Site Number 1560026
- Investigational Site Number 1560044
- Investigational Site Number 1560003
- Investigational Site Number 1580006
- Investigational Site Number 1580003
- Investigational Site Number 1580002
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Placebo
Efpeglenatide 2 mg
Efpeglenatide 4 mg
Efpeglenatide 6 mg
Arm Description
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.
Participants received Efpeglenatide 2 milligrams (mg) SC injection once weekly up to Week 30 on top of metformin alone or in combination with SU.
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.
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.
Outcomes
Primary Outcome Measures
Change From Baseline to Week 30 in HbA1c
This analysis included all Week 30 assessment values available.
Secondary Outcome Measures
Number of Participants With HbA1c <7.0%
Participants who had no available assessment for HbA1c <7% at Week 30 were considered as non-responders.
Change From Baseline to Week 30 in Fasting Plasma Glucose (FPG)
This analysis included all Week 30 assessment values available.
Change From Baseline to Week 30 in Body Weight
This analysis included all Week 30 assessment values available.
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
NCT ID
NCT03770728
First Posted
December 7, 2018
Last Updated
November 4, 2021
Sponsor
Sanofi
Collaborators
Hanmi Pharmaceutical Company Limited
1. Study Identification
Unique Protocol Identification Number
NCT03770728
Brief Title
Efficacy and Safety of Efpeglenatide Versus Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin Alone or in Combination With Sulfonylurea
Acronym
AMPLITUDE-S
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision to cancel TRIAL, not related to safety concern
Study Start Date
August 1, 2019 (Actual)
Primary Completion Date
November 28, 2020 (Actual)
Study Completion Date
December 27, 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
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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 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
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.
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
312 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Efpeglenatide 2 mg
Arm Type
Experimental
Arm Description
Participants received Efpeglenatide 2 milligrams (mg) SC injection once weekly up to Week 30 on top of metformin alone or in combination with SU.
Arm Title
Efpeglenatide 4 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Efpeglenatide 6 mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Efpeglenatide SAR439977
Intervention Description
Pharmaceutical form: solution for injection Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical form: solution for injection Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
Background therapy: Metformin alone or in combination with SU
Intervention Description
Pharmaceutical form: tablet Route of administration: oral, administered as per investigator and in accordance with local labeling.
Primary Outcome Measure Information:
Title
Change From Baseline to Week 30 in HbA1c
Description
This analysis included all Week 30 assessment values available.
Time Frame
Baseline to Week 30
Secondary Outcome Measure Information:
Title
Number of Participants With HbA1c <7.0%
Description
Participants who had no available assessment for HbA1c <7% at Week 30 were considered as non-responders.
Time Frame
Week 30
Title
Change From Baseline to Week 30 in Fasting Plasma Glucose (FPG)
Description
This analysis included all Week 30 assessment values available.
Time Frame
Baseline to Week 30
Title
Change From Baseline to Week 30 in Body Weight
Description
This analysis included all Week 30 assessment values available.
Time Frame
Baseline to Week 30
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 30
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 30
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 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.
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 8400042
City
Mesa
State/Province
Arizona
ZIP/Postal Code
85206
Country
United States
Facility Name
Investigational Site Number 8400051
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85020
Country
United States
Facility Name
Investigational Site Number 8400056
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85741
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 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 8400047
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80909
Country
United States
Facility Name
Investigational Site Number 8400046
City
Coral Gables
State/Province
Florida
ZIP/Postal Code
33134
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 8400044
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40503
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 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 8400048
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73111
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 8400043
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
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 1560005
City
Baotou
ZIP/Postal Code
014010
Country
China
Facility Name
Investigational Site Number 1560042
City
Beijing
ZIP/Postal Code
101199
Country
China
Facility Name
Investigational Site Number 1560053
City
Hangzhou
ZIP/Postal Code
310009
Country
China
Facility Name
Investigational Site Number 1560051
City
Hefei
ZIP/Postal Code
210011
Country
China
Facility Name
Investigational Site Number 1560011
City
Hunan
ZIP/Postal Code
411100
Country
China
Facility Name
Investigational Site Number 1560025
City
Meihekou
ZIP/Postal Code
135000
Country
China
Facility Name
Investigational Site Number 1560055
City
Nanchang
ZIP/Postal Code
330006
Country
China
Facility Name
Investigational Site Number 1560024
City
Nanjing
ZIP/Postal Code
210011
Country
China
Facility Name
Investigational Site Number 1560020
City
Pingxiang
ZIP/Postal Code
337055
Country
China
Facility Name
Investigational Site Number 1560031
City
Shandong
ZIP/Postal Code
250013
Country
China
Facility Name
Investigational Site Number 1560030
City
Shandong
ZIP/Postal Code
250031
Country
China
Facility Name
Investigational Site Number 1560012
City
Shanghai
ZIP/Postal Code
200040
Country
China
Facility Name
Investigational Site Number 1560013
City
Shanghai
ZIP/Postal Code
200040
Country
China
Facility Name
Investigational Site Number 1560004
City
Shanghai
ZIP/Postal Code
200065
Country
China
Facility Name
Investigational Site Number 1560022
City
Shanghai
ZIP/Postal Code
200090
Country
China
Facility Name
Investigational Site Number 1560041
City
Tianjin
ZIP/Postal Code
300052
Country
China
Facility Name
Investigational Site Number 1560010
City
Wenzhou
ZIP/Postal Code
325027
Country
China
Facility Name
Investigational Site Number 1560052
City
Wuhu
ZIP/Postal Code
241001
Country
China
Facility Name
Investigational Site Number 1560034
City
Wuxi
ZIP/Postal Code
214000
Country
China
Facility Name
Investigational Site Number 1560026
City
Xuzhou
ZIP/Postal Code
221006
Country
China
Facility Name
Investigational Site Number 1560044
City
Yichun
ZIP/Postal Code
336000
Country
China
Facility Name
Investigational Site Number 1560003
City
Zhengzhou
ZIP/Postal Code
450003
Country
China
Facility Name
Investigational Site Number 1580006
City
Kaohsiung
ZIP/Postal Code
83301
Country
Taiwan
Facility Name
Investigational Site Number 1580003
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
Investigational Site Number 1580002
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
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 Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin Alone or in Combination With Sulfonylurea
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