Back to resultsEfficacy 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) (AMPLITUDE-L)
Primary Purpose
Type 2 Diabetes Mellitus
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Efpeglenatide SAR439977
Placebo
Background therapy
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 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.
Sites / Locations
- Investigational Site Number 8400038
- Investigational Site Number 8400035
- Investigational Site Number 8400005
- Investigational Site Number 8400057
- Investigational Site Number 8400058
- Investigational Site Number 8400009
- Investigational Site Number 8400045
- Investigational Site Number 8400040
- Investigational Site Number 8400026
- Investigational Site Number 8400055
- Investigational Site Number 8400041
- Investigational Site Number 8400025
- Investigational Site Number 8400052
- Investigational Site Number 8400044
- Investigational Site Number 8400001
- Investigational Site Number 8400039
- Investigational Site Number 8400036
- Investigational Site Number 8400013
- Investigational Site Number 8400030
- Investigational Site Number 8400063
- Investigational Site Number 8400043
- Investigational Site Number 8400037
- Investigational Site Number 1560005
- Investigational Site Number 1560017
- Investigational Site Number 1560006
- Investigational Site Number 1560001
- Investigational Site Number 1560004
- Investigational Site Number 1560036
- Investigational Site Number 1560012
- Investigational Site Number 1560013
- Investigational Site Number 1560003
- Investigational Site Number 4100009
- Investigational Site Number 4100001
- Investigational Site Number 4100016
- Investigational Site Number 4100010
- Investigational Site Number 4100013
- Investigational Site Number 4100015
- Investigational Site Number 4100014
- Investigational Site Number 4100007
- Investigational Site Number 4100008
- Investigational Site Number 4100002
- Investigational Site Number 4100005
- Investigational Site Number 4100004
- Investigational Site Number 4100003
- Investigational Site Number 4100011
- Investigational Site Number 4100006
- Investigational Site Number 4100012
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 56 on top of basal insulin alone or in combination with oral antidiabetic drugs (OADs).
Participants received Efpeglenatide 2 milligrams (mg) SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs.
Participants received Efpeglenatide 4 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg and maintained at the 4 mg dose through-out the treatment duration up to Week 56.
Participants received Efpeglenatide 6 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg until Week 4 and later up-titrated to 6 mg and maintained at the 6 mg dose through-out the treatment duration up to Week 56.
Outcomes
Primary Outcome Measures
Change From Baseline to Week 30 in HbA1c
Secondary Outcome Measures
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.
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.
Change From Baseline to Week 30 in Fasting Plasma Glucose (FPG)
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.
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.
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
NCT03713684
First Posted
October 18, 2018
Last Updated
November 4, 2021
Sponsor
Sanofi
Collaborators
Hanmi Pharmaceutical Company Limited
1. Study Identification
Unique Protocol Identification Number
NCT03713684
Brief Title
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)
Acronym
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)
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
November 9, 2018 (Actual)
Primary Completion Date
November 20, 2020 (Actual)
Study Completion Date
January 4, 2021 (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 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.
Detailed 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.
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
370 (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 56 on top of basal insulin alone or in combination with oral antidiabetic drugs (OADs).
Arm Title
Efpeglenatide 2 mg
Arm Type
Experimental
Arm Description
Participants received Efpeglenatide 2 milligrams (mg) SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs.
Arm Title
Efpeglenatide 4 mg
Arm Type
Experimental
Arm Description
Participants received Efpeglenatide 4 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg and maintained at the 4 mg dose through-out the treatment duration up to Week 56.
Arm Title
Efpeglenatide 6 mg
Arm Type
Experimental
Arm Description
Participants received Efpeglenatide 6 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg until Week 4 and later up-titrated to 6 mg and maintained at the 6 mg dose through-out the treatment duration up to Week 56.
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
Intervention Description
Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.
Primary Outcome Measure Information:
Title
Change From Baseline to Week 30 in HbA1c
Time Frame
Baseline to Week 30
Secondary Outcome Measure Information:
Title
Number of Participants With HbA1c <7.0% at Week 30
Description
Participants who had no available assessment for HbA1c at Week 30 were considered as non-responders.
Time Frame
Week 30
Title
Change From Baseline to Week 56 in HbA1c
Description
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.
Time Frame
Baseline to Week 56
Title
Change From Baseline to Week 30 in Fasting Plasma Glucose (FPG)
Time Frame
Baseline to Week 30
Title
Change From Baseline to Week 30 and Week 56 in Body Weight
Description
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.
Time Frame
Baseline to Week 30 and Week 56
Title
Number of Participants With At Least One Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL], and 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 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 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.
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 8400057
City
Huntington Park
State/Province
California
ZIP/Postal Code
90255
Country
United States
Facility Name
Investigational Site Number 8400058
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
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 8400026
City
Van Nuys
State/Province
California
ZIP/Postal Code
91405
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 8400052
City
West Des Moines
State/Province
Iowa
ZIP/Postal Code
50265
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 8400030
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Investigational Site Number 8400063
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9302
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 1560017
City
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Investigational Site Number 1560006
City
Changsha
ZIP/Postal Code
410013
Country
China
Facility Name
Investigational Site Number 1560001
City
Chengdu
ZIP/Postal Code
610083
Country
China
Facility Name
Investigational Site Number 1560004
City
Shanghai
ZIP/Postal Code
014010
Country
China
Facility Name
Investigational Site Number 1560036
City
Shanghai
ZIP/Postal Code
200032
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 1560003
City
Zhengzhou
ZIP/Postal Code
450003
Country
China
Facility Name
Investigational Site Number 4100009
City
Busan
ZIP/Postal Code
49241
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100001
City
Daejeon
ZIP/Postal Code
35233
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100016
City
Gwangju
ZIP/Postal Code
501757
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100010
City
Gwangju
ZIP/Postal Code
61453
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100013
City
Gyeonggi-do
ZIP/Postal Code
11765
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100015
City
Incheon
ZIP/Postal Code
21565
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100014
City
Jeonju
ZIP/Postal Code
54907
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100007
City
Seongnam-Si
ZIP/Postal Code
13620
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100008
City
Seoul
ZIP/Postal Code
02447
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100002
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100005
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100004
City
Seoul
ZIP/Postal Code
05278
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100003
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100011
City
Seoul
ZIP/Postal Code
07345
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100006
City
Seoul
ZIP/Postal Code
14647
Country
Korea, Republic of
Facility Name
Investigational Site Number 4100012
City
Suwon
ZIP/Postal Code
16247
Country
Korea, Republic of
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 Basal Insulin Alone or in Combination With Oral Antidiabetic Drug(s)
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