Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

NCTNCT02973321Other idDRI13940Other id2016-001328-77Other idU1111-1179-4786Other id2016

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 2
Enrollment: 296 participants (actual)
Sponsor: Sanofi · Industry
Design: Randomized · Quadruple masking
Countries: 8 countries
United States, Canada, Czechia, Germany, Hungary, Mexico, Russia, Spain
Start: 2 Dec 2016
Primary completion: 27 Dec 2017
Completion: 27 Dec 2017
First posted: 25 Nov 2016 (estimated)
Last update posted: 24 Mar 2022
Conditions: Type 2 Diabetes Mellitus

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

201620172018

Ph 2
A Study to Assess the Safety and Efficacy of SAR425899 in Patients With Type 2 Diabetes Mellitus
NCT02973321
2 Dec 2016 to 27 Dec 2017

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

SAR425899Drug
PlaceboDrug
LiraglutideDrug
MetforminDrug

Arms5

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.
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).
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).
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).
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).

Primary outcomes1

Outcomes the sponsor listed as primary.

Change From Baseline in HbA1c to Week 26
Time frame · Baseline, Week 26
Registry description
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 outcomes(9)

Mean Change From Baseline in Body Weight to Week 26
Time frame · Baseline, Week 26
Registry description
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.
Percentage of Participants Reached HbA1c Target of <6.5% or <7% at Week 26
Time frame · Week 26
Registry description
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.
Percentage of Participants Achieving >=5% or >=10% Body Weight Loss at Week 26
Time frame · Week 26
Registry description
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.
Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26
Time frame · Baseline, Week 26
Registry description
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.
Change From Baseline in Average 7 Point Self-Monitoring Plasma Glucose (SMPG) to Week 26
Time frame · Baseline, Week 26
Registry description
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.
Percentage of Participants Requiring Rescue Therapy
Time frame · Baseline up to 26 weeks
Registry description
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.
Change From Baseline in Beta-Cell Function to Week 26
Time frame · Baseline, Week 26
Registry description
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.
Change From Baseline in Insulin Resistance to Week 26
Time frame · Baseline, Week 26
Registry description
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.
Change From Baseline in Pharmacodynamic Biomarkers to Week 26 - Waist and Hip Circumferences
Time frame · Baseline,Week 26
Registry description
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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline, Week 26

Change From Baseline in HbA1c to Week 26

Group	Value (percentage of HbA1c)	Spread
Placebo	-0.663	0.169
SAR425899 0.12 mg	-1.517	0.137
SAR425899 0.16 mg	-1.618	0.133
SAR425899 0.20 mg	-1.562	0.131
Liraglutide	-1.312	0.118

Secondary and other outcome results(7)

Secondary outcomeLeast squares mean· Baseline, Week 26

Mean Change From Baseline in Body Weight to Week 26

Group	Value (Kg)	Spread
Placebo	-1.759	0.734
SAR425899 0.12 mg	-4.276	0.564
SAR425899 0.16 mg	-5.330	0.549
SAR425899 0.20 mg	-4.407	0.559
Liraglutide	-4.590	0.521

Secondary outcomeNumber· Week 26

Percentage of Participants Reached HbA1c Target of <6.5% or <7% at Week 26

Group	Value (percentage of participants)
Placebo	12.1
SAR425899 0.12 mg	47.0
SAR425899 0.16 mg	51.5
SAR425899 0.20 mg	48.4
Liraglutide	44.8

Secondary outcomeNumber· Week 26

Percentage of Participants Achieving >=5% or >=10% Body Weight Loss at Week 26

Group	Value (percentage of participants)
Placebo	3.0
SAR425899 0.12 mg	33.3
SAR425899 0.16 mg	45.5
SAR425899 0.20 mg	35.9
Liraglutide	40.3

Secondary outcomeLeast squares mean· Baseline, Week 26

Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26

Group	Value (mmol/L)	Spread
Placebo	-0.931	0.394
SAR425899 0.12 mg	-2.408	0.308
SAR425899 0.16 mg	-2.548	0.301
SAR425899 0.20 mg	-2.318	0.312
Liraglutide	-2.124	0.280

Secondary outcomeMean· Baseline, Week 26

Change From Baseline in Average 7 Point Self-Monitoring Plasma Glucose (SMPG) to Week 26

Group	Value (mmol/L)	Spread
Placebo	-1.82	3.11
SAR425899 0.12 mg	-2.86	2.62
SAR425899 0.16 mg	-2.63	2.70
SAR425899 0.20 mg	-2.49	3.18
Liraglutide	-2.21	2.23

Secondary outcomeNumber· Baseline up to 26 weeks

Percentage of Participants Requiring Rescue Therapy

Group	Value (percentage of participants)
Placebo	18.2
SAR425899 0.12 mg	0.0
SAR425899 0.16 mg	1.5
SAR425899 0.20 mg	3.1
Liraglutide	6.0

Secondary outcomeLeast squares mean· Baseline, Week 26

Change From Baseline in Beta-Cell Function to Week 26

Group	Value (percentage of normal beta cells function)	Spread
Placebo	15.025	19.785
SAR425899 0.12 mg	26.768	15.833
SAR425899 0.16 mg	31.122	16.467
SAR425899 0.20 mg	17.932	14.397
Liraglutide	27.263	13.234

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
PlaceboPlacebo (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.	0 / 33	0 / 33	10 / 33
SAR425899 0.06 mgParticipants who were originally randomized to SAR425899 treatment groups and received 0.06 mg QD at Week 8.	0 / 18	2 / 18	18 / 18
SAR425899 0.12 mgParticipants who were originally randomized to SAR425899 treatment groups and received 0.12 mg QD at Week 8, or participants randomized to SAR425899 0.12 mg treatment group and discontinued the study before Week 8.	0 / 72	3 / 72	49 / 72
SAR425899 0.16 mgParticipants who were originally randomized to SAR425899 treatment groups and received 0.16 mg QD at Week 8, or participants randomized to SAR425899 0.16 mg treatment group and discontinued the study before Week 8.	0 / 59	1 / 59	45 / 59
SAR425899 0.20 mgParticipants who were originally randomized to SAR425899 treatment groups and received 0.20 mg QD at Week 8, or participants randomized to SAR425899 0.20 mg treatment group and discontinued the study before Week 8.	0 / 47	2 / 47	34 / 47
LiraglutideParticipants randomized to and received Liraglutide treatment were included in the Liraglutide treatment arm regardless of dose amount participants received.	0 / 67	2 / 67	34 / 67

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2021

5 results

Improved postprandial glucose metabolism in type 2 diabetes by the dual glucagon-like peptide-1/glucagon receptor agonist SAR425899 in comparison with liraglutide.

Schiavon et al. 2021Diabetes, obesity & metabolismcited by 42

PMID 33822469PMC8359969DOI 10.1111/dom.14394PUB-33822469

Free to read · publisher termsCC BY-NC5 results

Read at source See results (5)

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

DerivedGater A, Reaney M, Findley A, Brun-Strang C, Burrows K, Nguyen-Pascal ML, Roborel de Climens A. Development and First Use of the Patient's Qualitative Assessment of Treatment (PQAT) Questionnaire in Type 2 Diabetes Mellitus to Explore Individualised Benefit-Harm of Drugs Received During Clinical Studies. Drug Saf. 2020 Feb;43(2):119-134. doi: 10.1007/s40264-019-00877-4. PMID 31679129

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years up to 80 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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.

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