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

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ClinicalTrials.gov Identifier: NCT03684642
Recruitment Status : Terminated (Sponsor decision to cancel TRIAL, not related to safety concern.)
First Posted : September 26, 2018
Results First Posted : November 1, 2021
Last Update Posted : November 1, 2021
Sponsor:
Collaborator:
Hanmi Pharmaceutical Company Limited
Information provided by (Responsible Party):
Sanofi

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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Efpeglenatide Drug: Dulaglutide Drug: Background therapy Metformin Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 908 participants
Allocation: Randomized
Intervention 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.
Primary Purpose: Treatment
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
Actual Study Start Date : September 26, 2018
Actual Primary Completion Date : October 13, 2020
Actual Study Completion Date : November 17, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Efpeglenatide 4 mg
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.
Drug: Efpeglenatide
Pharmaceutical form: solution for injection; Route of administration: SC
Other Name: SAR439977

Drug: Background therapy Metformin
Pharmaceutical form: tablet; Route of administration: oral; Dose to be kept stable throughout the study.

Experimental: Efpeglenatide 6 mg
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.
Drug: Efpeglenatide
Pharmaceutical form: solution for injection; Route of administration: SC
Other Name: SAR439977

Drug: Background therapy Metformin
Pharmaceutical form: tablet; Route of administration: oral; Dose to be kept stable throughout the study.

Active Comparator: Dulaglutide 1.5 mg
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.
Drug: Dulaglutide
Pharmaceutical form: solution for injection; Route of administration: SC
Other Name: Trulicity™

Drug: Background therapy Metformin
Pharmaceutical form: tablet; Route of administration: oral; Dose to be kept stable throughout the study.




Primary Outcome Measures :
  1. Change From Baseline to Week 56 in HbA1c [ Time Frame: Baseline to Week 56 ]
    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 :
  1. Change From Baseline to Week 56 in Body Weight [ Time Frame: Baseline to Week 56 ]
    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.

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

  3. Change From Baseline to Week 56 in Fasting Plasma Glucose (FPG) [ Time Frame: Baseline to Week 56 ]
    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.

  4. Number of Participants With At Least One Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL], Severe Hypoglycemia) [ Time Frame: Baseline up to Week 56 ]
    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.

  5. Number of Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL] and Severe Hypoglycemia) Per Participant-Year [ Time Frame: Baseline up to Week 56 ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03684642


Locations
Show Show 45 study locations
Sponsors and Collaborators
Sanofi
Hanmi Pharmaceutical Company Limited
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] July 31, 2019
Statistical Analysis Plan  [PDF] October 2, 2020

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03684642    
Other Study ID Numbers: EFC14829
2017-002956-10 ( EudraCT Number )
U1111-1205-3150 ( Other Identifier: UTN )
First Posted: September 26, 2018    Key Record Dates
Results First Posted: November 1, 2021
Last Update Posted: November 1, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to share individual participant data (IPD) by SANOFI: Product rights transferred to Hanmi Pharmaceutical.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Dulaglutide
Efpeglenatide
Hypoglycemic Agents
Physiological Effects of Drugs