Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    DRI13940
Previous Study | Return to List | Next Study

A Study to Assess the Safety and Efficacy of SAR425899 in Patients With Type 2 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02973321
Recruitment Status : Completed
First Posted : November 25, 2016
Results First Posted : February 9, 2021
Last Update Posted : February 9, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

The primary objective of this study was to assess the dose-response relationship of SAR425899 versus placebo in terms of glycemic control as measured by the change in glycosylated hemoglobin (HbA1c).

Secondary Objectives:

  • To assess the effect of SAR425899 on body weight.
  • To assess the safety and immunogenicity profile of SAR425899, including assessment of the heart rate (HR) change by electrocardiogram (ECG) and Holter monitor.
  • To assess the proportion of participants achieving predefined HbA1c targets of <7% and <6.5% as well as the proportion of participants achieving >=5% and >=10% body weight loss.
  • To assess the effect of once daily dosing of SAR425899 on additional parameters of glycemic control and lipid metabolism.
  • To assess the effect of once daily dosing of SAR425899 on additional pharmacodynamic (PD) biomarkers.
  • To assess the pharmacokinetic (PK) profile and parameters of SAR425899, inter-individual and inter-occasion variability in PK parameters using a population PK approach.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: SAR425899 Drug: Placebo Drug: Liraglutide Drug: Metformin Phase 2

Detailed Description:
The total study duration will be approximately 30 weeks, consisting of 3 weeks screening period at the site, a 26 weeks treatment period, and 3 days post treatment follow up period.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 296 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 26-Week Randomized, Double-blind, Placebo-controlled, Dose-ranging Phase 2 Study to Assess the Safety and Efficacy of SAR425899 in Patients With Type 2 Diabetes Mellitus
Actual Study Start Date : December 2, 2016
Actual Primary Completion Date : December 27, 2017
Actual Study Completion Date : December 27, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Liraglutide

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo (for SAR425899) subcutaneous (SC) injection once daily (QD) from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
Drug: Placebo
Self-administered by SC injection using a solution for injection in cartridge.

Drug: Metformin
Orally administered at a stable dose , >=1500 mg daily stable dose or maximal tolerated dose.

Experimental: SAR425899 0.12 mg
SAR425899 SC injection QD at maintenance dose of 0.12 mg for 25 weeks (Week 2 to Week 26) following 1 week dose increase step (0.06 mg at Week 1).
Drug: SAR425899
Self-administered by SC injection using a solution for injection in cartridge.

Drug: Metformin
Orally administered at a stable dose , >=1500 mg daily stable dose or maximal tolerated dose.

Experimental: SAR425899 0.16 mg
SAR425899 SC injection QD at maintenance dose of 0.16 mg for 24 weeks (Week 3 to Week 26) following 2 weeks dose increase step (0.06 mg at Week 1 and 0.12 mg at Week 2).
Drug: SAR425899
Self-administered by SC injection using a solution for injection in cartridge.

Drug: Metformin
Orally administered at a stable dose , >=1500 mg daily stable dose or maximal tolerated dose.

Experimental: SAR425899 0.20 mg
SAR425899 SC injection QD at maintenance dose of 0.20 mg for 23 weeks (Week 4 to Week 26) following 3 weeks dose increase step (0.06 mg at Week 1, 0.12 mg at Week 2 and 0.16 mg at Week 3).
Drug: SAR425899
Self-administered by SC injection using a solution for injection in cartridge.

Drug: Metformin
Orally administered at a stable dose , >=1500 mg daily stable dose or maximal tolerated dose.

Active Comparator: Liraglutide
Liraglutide SC injection QD at maintenance dose of 1.8 mg for 24 weeks (Week 3 to Week 26) following 2 weeks dose increase steps (0.6 mg daily at Week 1 and by 1.2 mg daily at Week 2).
Drug: Liraglutide
Self-administered by SC injection using a pre-filled pen.
Other Name: Victoza

Drug: Metformin
Orally administered at a stable dose , >=1500 mg daily stable dose or maximal tolerated dose.




Primary Outcome Measures :
  1. Change From Baseline in HbA1c to Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Missing post-baseline values were imputed by placebo control-based multiple imputation (MI) method under the missing not at random framework.


Secondary Outcome Measures :
  1. Mean Change From Baseline in Body Weight to Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in body weight was calculated by subtracting baseline value from Week 26 value. Missing post- baseline values were imputed by placebo control-based MI method under the missing not at random framework.

  2. Percentage of Participants Reached HbA1c Target of <6.5% or <7% at Week 26 [ Time Frame: Week 26 ]
    The analysis included assessment collected during the study, including those obtained after IMP discontinuation or introduction of rescue therapy. Participants with no measurement at Week 26 were treated as non-responders.

  3. Percentage of Participants Achieving >=5% or >=10% Body Weight Loss at Week 26 [ Time Frame: Week 26 ]
    The analysis included assessment collected during the study, including those obtained after IMP discontinuation or introduction of rescue therapy. Participants with no measurement at Week 26 were treated as non-responders.

  4. Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in FPG was calculated by subtracting baseline value from Week 26 value. Missing post-baseline values were imputed by placebo control-based MI method under the missing not at random framework.

  5. Change From Baseline in Average 7 Point Self-Monitoring Plasma Glucose (SMPG) to Week 26 [ Time Frame: Baseline, Week 26 ]
    Change in 7-point SMPG profile from baseline to Week 26 was assessed by summary statistics. 7-point SMPG profiles were measured at the following 7 points at each visit (Baseline, and Week 26): pre-prandial and 2 hours postprandial for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) is defined as 2 hours after the start of the meal.

  6. Percentage of Participants Requiring Rescue Therapy [ Time Frame: Baseline up to 26 weeks ]
    Rescue medication was introduced in case FPG or HbA1c values were above pre-defined thresholds, and if no reasons were found for insufficient glucose control, and appropriate action failed to decrease FPG / HbA1c under the threshold values (from baseline to Week 8: FPG >270 mg/dL 15.0 mmol/L, from Week 8 to Week 14: FPG >13.3 mmol/L, and from Week 14 to Week 26: FPG >11.1 mmol/L or HbA1c>8%). The choice of rescue therapy was at the Investigator's discretion with the exception of using glucagon-like peptide-1 receptor (GLP-1R) agonists or dipeptidyl peptidase 4 (DPP4) inhibitors.

  7. Change From Baseline in Beta-Cell Function to Week 26 [ Time Frame: Baseline, Week 26 ]
    Beta-cell function was assessed by homeostatic model assessment (HOMA)-beta, derived from FPG and fasting plasma insulin (FPI). HOMA-beta was derived from FPG and FPI as (20*FPI [micro units/milliliter]) divided by (FPG [mmol/L] minus 3.5). Change was calculated for HOMA-beta by subtracting the Baseline value from Week 26 value*100.

  8. Change From Baseline in Insulin Resistance to Week 26 [ Time Frame: Baseline, Week 26 ]
    Insulin Resistance was assessed by homeostasis model assessment for insulin resistance (HOMA-IR), derived from FPG and FPI. HOMA-IR was derived from FPG and FPI as (FPI [micro units per milliliter] * FPG [mmol/L]) divided by 22.5. Change was calculated for HOMA-beta by subtracting the Baseline value from Week 26 value.

  9. Change From Baseline in Pharmacodynamic Biomarkers to Week 26 - Waist and Hip Circumferences [ Time Frame: Baseline,Week 26 ]
    Waist circumference was measured at the midpoint between the lower margin of the least palpable rib and the top of the iliac crest, using a stretch-resistant tape providing a constant 100 gm tension. Hip circumference was measured around the widest portion of the buttocks, with the tape parallel to the floor. Each measurement was repeated twice; if the measurements were within 1 cm of one another, the average was calculated, and if the difference exceeded 1 cm, the measurements were repeated.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Participants with type-2 diabetes mellitus (T2DM) for at least 3 months before the screening visit.
  • On diet/exercise and/or treatment with metformin (stable dose of ≥1500 mg/day or maximal tolerated dose) for at least 3 months prior to screening.
  • Signed informed consent.

Exclusion criteria:

  • At screening, participant's age < legal age of adulthood and >80 years.
  • Glycated hemoglobin at screening visit <7.0% or >10.0%.
  • Body mass index (BMI) <25 kg/m^2 or >45.0 kg/m^2.
  • Pregnant or lactating women.
  • Women of childbearing potential (WOCBP) not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy.
  • Diagnosis of type 1 diabetes mellitus.
  • Fasting plasma glucose of >15 mmol/L (270 mg/dL) measured by the central laboratory at screening (Visit 1), and confirmed (>15 mmol/L [270 mg/dL]) by a repeat test before randomization.
  • Treatment with glucose-lowering agents(s) other than metformin, currently or within the 3 months prior to screening.
  • Previous insulin use, except for episode(s) of short-term treatment (≤15 consecutive days) for intercurrent illness or pregnancy, or use of insulin within the last 6 months.
  • Contraindication(s) to metformin use.
  • Contraindication(s) to liraglutide use.
  • Significant change in body weight in the 3 months before screening.
  • Poorly controlled hypertension (a resting systolic blood pressure (SBP) >160 mm Hg and/or diastolic blood pressure (DBP) >95 mm Hg at screening).
  • History of long QT syndrome and/or QTc more than 450 ms at screening visit.
  • History of pancreatitis or pancreatectomy.
  • History of weight loss surgery.
  • Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC.
  • Any prior exposure to drugs belonging to the class of glucagon-like peptide-1 (GLP-1) receptor agonists/GLP-1 analogs.
  • Contraindications or known hypersensitivity reaction to glucagon.

The above information is 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): NCT02973321


Locations
Show Show 59 study locations
Sponsors and Collaborators
Sanofi
Investigators
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] January 23, 2017
Statistical Analysis Plan  [PDF] September 18, 2017

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02973321    
Other Study ID Numbers: DRI13940
2016-001328-77 ( EudraCT Number )
U1111-1179-4786 ( Other Identifier: UTN )
First Posted: November 25, 2016    Key Record Dates
Results First Posted: February 9, 2021
Last Update Posted: February 9, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available we continue to protect the privacy of the participants in our clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Liraglutide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists