A Study to Assess the Safety and Efficacy of SAR425899 in... | NCT02973321 | Trialant
NCT02973321
Sponsor
Sanofi
Status
Completed
Last Update Posted
Mar 24, 2022Actual
Enrollment
296Actual
Phase
Phase 2
Conditions
Type 2 Diabetes Mellitus
Interventions
SAR425899
Placebo
Liraglutide
Metformin
Countries
United States
Canada
Czechia
Germany
Hungary
Mexico
Russia
Spain
Protocol Section
Identification Module
NCT ID
NCT02973321
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
DRI13940
Secondary IDs
ID
Type
Description
Link
2016-001328-77
EudraCT Number
U1111-1179-4786
Other Identifier
UTN
Brief Title
A Study to Assess the Safety and Efficacy of SAR425899 in Patients With Type 2 Diabetes Mellitus
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
Acronym
Not provided
Organization
SanofiINDUSTRY
Status Module
Record Verification Date
Mar 2022
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Dec 2, 2016Actual
Primary Completion Date
Dec 27, 2017Actual
Completion Date
Dec 27, 2017Actual
First Submitted Date
Nov 22, 2016
First Submission Date that Met QC Criteria
Nov 22, 2016
First Posted Date
Nov 25, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Dec 3, 2020
Results First Submitted that Met QC Criteria
Jan 21, 2021
Results First Posted Date
Feb 9, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Dec 4, 2018
Certification/Extension First Submitted that Passed QC Review
Dec 4, 2018
Certification/Extension First Posted Date
Dec 7, 2018Actual
Last Update Submitted Date
Mar 15, 2022
Last Update Posted Date
Mar 24, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
SanofiINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
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.
Conditions Module
Conditions
Type 2 Diabetes Mellitus
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
296Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo
Placebo Comparator
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
Drug: Metformin
SAR425899 0.12 mg
Experimental
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
Drug: Metformin
SAR425899 0.16 mg
Experimental
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
Drug: Metformin
SAR425899 0.20 mg
Experimental
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
Drug: Metformin
Liraglutide
Active Comparator
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).
Interventions
Name
Type
Description
Arm Group Labels
Other Names
SAR425899
Drug
Self-administered by SC injection using a solution for injection in cartridge.
SAR425899 0.12 mg
SAR425899 0.16 mg
SAR425899 0.20 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change From Baseline in HbA1c to 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.
Baseline, Week 26
Secondary Outcomes
Measure
Description
Time Frame
Mean Change From Baseline in Body Weight to 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.
Baseline, Week 26
Percentage of Participants Reached HbA1c Target of <6.5% or <7% at Week 26
Other Outcomes
Not provided
Eligibility Module
Eligibility 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.
Schiavon M, Visentin R, Gobel B, Riz M, Cobelli C, Klabunde T, Dalla Man C. Improved postprandial glucose metabolism in type 2 diabetes by the dual glucagon-like peptide-1/glucagon receptor agonist SAR425899 in comparison with liraglutide. Diabetes Obes Metab. 2021 Aug;23(8):1795-1805. doi: 10.1111/dom.14394. Epub 2021 May 5.
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Total of 294 participants were randomized using interactive response technology, however 2 participants were screened failures and were randomized by error in liraglutide and SAR425899 0.20 mg groups, therefore a total of 296 participants were randomized and treated in study. Randomization was stratified by glycosylated hemoglobin(HbA1c) at screening visit(<8% vs >=8%) and body mass index (BMI)(<35.0 kg/m^2 vs >=35.0kg/m^2) at Day 1(start of investigational medicinal product[IMP]administration).
Recruitment Details
The study was conducted at 59 centers in 8 countries. A total of 539 participants were screened between 2 December 2016 and 2 June 2017, of whom, 245 participants were screen failures. Screen failures were mainly due to exclusion criteria met. The study was double-blind for SAR425899 vs placebo and open-label for active comparator liraglutide.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
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.
Self-administered by SC injection using a solution for injection in cartridge.
Placebo
Liraglutide
Drug
Self-administered by SC injection using a pre-filled pen.
Liraglutide
Victoza
Metformin
Drug
Orally administered at a stable dose , >=1500 mg daily stable dose or maximal tolerated dose.
Liraglutide
Placebo
SAR425899 0.12 mg
SAR425899 0.16 mg
SAR425899 0.20 mg
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.
Week 26
Percentage of Participants Achieving >=5% or >=10% Body Weight Loss at 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.
Week 26
Change From Baseline in Fasting Plasma Glucose (FPG) to 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.
Baseline, Week 26
Change From Baseline in Average 7 Point Self-Monitoring Plasma Glucose (SMPG) to 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.
Baseline, Week 26
Percentage of Participants Requiring Rescue Therapy
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.
Baseline up to 26 weeks
Change From Baseline in Beta-Cell Function to 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.
Baseline, Week 26
Change From Baseline in Insulin Resistance to 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.
Baseline, Week 26
Change From Baseline in Pharmacodynamic Biomarkers to Week 26 - Waist and Hip Circumferences
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.
Baseline,Week 26
Huntington Park
California
90255
United States
Investigational Site Number 8400024
Los Angeles
California
90017
United States
Investigational Site Number 8400001
Los Angeles
California
90057
United States
Investigational Site Number 8400012
Port Hueneme
California
93041
United States
Investigational Site Number 8400027
Denver
Colorado
80209
United States
Investigational Site Number 8400025
Miami
Florida
33166
United States
Investigational Site Number 8400007
Palm Harbor
Florida
34684
United States
Investigational Site Number 8400013
Chicago
Illinois
60827
United States
Investigational Site Number 8400016
Wichita
Kansas
67205
United States
Investigational Site Number 8400023
Wichita
Kansas
67207
United States
Investigational Site Number 8400018
New Orleans
Louisiana
70119
United States
Investigational Site Number 8400019
Rockville
Maryland
20852
United States
Investigational Site Number 8400014
Flint
Michigan
48532-3447
United States
Investigational Site Number 8400003
Troy
Michigan
48085
United States
Investigational Site Number 8400020
Linden
New Jersey
07036
United States
Investigational Site Number 8400022
New York
New York
10001
United States
Investigational Site Number 8400005
Fargo
North Dakota
58103
United States
Investigational Site Number 8400004
Austin
Texas
78731
United States
Investigational Site Number 8400006
Dallas
Texas
75230
United States
Investigational Site Number 8400021
Houston
Texas
77079
United States
Investigational Site Number 8400026
San Antonio
Texas
78229
United States
Investigational Site Number 8400017
Sugar Land
Texas
77478
United States
Investigational Site Number 1240008
Québec
G1S 2L6
Canada
Investigational Site Number 1240005
Sainte-Foy
G1W4R4
Canada
Investigational Site Number 1240002
Sherbrooke
J1L 0H8
Canada
Investigational Site Number 1240001
Toronto
M4G 3E8
Canada
Investigational Site Number 1240003
Vancouver
V5Y 3W2
Canada
Investigational Site Number 2030003
České Budějovice
370 01
Czechia
Investigational Site Number 2030001
Krnov
79401
Czechia
Investigational Site Number 2030004
Praha 10 - Uhrineves
104 00
Czechia
Investigational Site Number 2030002
Praha 9 - Klanovice
19014
Czechia
Investigational Site Number 2760003
Berlin
10115
Germany
Investigational Site Number 2760001
Dresden
01307
Germany
Investigational Site Number 2760006
Hohenmölsen
06679
Germany
Investigational Site Number 3480001
Balatonfüred
8230
Hungary
Investigational Site Number 3480002
Budapest
1027
Hungary
Investigational Site Number 3480008
Budapest
1042
Hungary
Investigational Site Number 3480005
Budapest
1062
Hungary
Investigational Site Number 3480006
Budapest
1062
Hungary
Investigational Site Number 3480007
Budapest
1213
Hungary
Investigational Site Number 4840004
Actopan
42500
Mexico
Investigational Site Number 4840001
Guadalajara
44600
Mexico
Investigational Site Number 4840003
Guadalajara
44670
Mexico
Investigational Site Number 4840002
Monterrey
64460
Mexico
Investigational Site Number 4840006
San Juan del Río
76800
Mexico
Investigational Site Number 6430002
Saint Petersburg
190068
Russia
Investigational Site Number 6430004
Saint Petersburg
194358
Russia
Investigational Site Number 6430001
Saint Petersburg
195257
Russia
Investigational Site Number 6430003
Saratov
410030
Russia
Investigational Site Number 6430005
Voronezh
394018
Russia
Investigational Site Number 7240001
A Coruña
15006
Spain
Investigational Site Number 7240005
Barcelona
08035
Spain
Investigational Site Number 7240007
Ferrol
15405
Spain
Investigational Site Number 7240006
Las Palmas de Gran Canaria
35016
Spain
Investigational Site Number 7240002
Madrid
28040
Spain
Investigational Site Number 7240003
Málaga
29010
Spain
Investigational Site Number 7240004
Málaga
29010
Spain
Investigational Site Number 7240008
Seville
41071
Spain
Derived
Gater 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.
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).
FG002
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).
FG003
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).
FG004
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).
FG00033 subjects
FG00166 subjects
FG00266 subjects
FG00364 subjects
FG00467 subjects
COMPLETED
FG00032 subjects
FG00151 subjects
FG00252 subjects
FG00348 subjects
FG00462 subjects
NOT COMPLETED
FG0001 subjects
FG00115 subjects
FG00214 subjects
FG00316 subjects
FG0045 subjects
Type
Comment
Reasons
Other than specified
FG0000 subjects
FG0015 subjects
FG0023 subjects
FG0033 subjects
FG0041 subjects
Lack of Efficacy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Adverse Event
FG0001 subjects
FG00110 subjects
FG00211 subjects
FG00313 subjects
FG004
Analysis was performed on all randomized participants.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo
Placebo (for SAR425899) SC injection QD from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
BG001
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).
BG002
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).
BG003
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).
BG004
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).
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00033
BG00166
BG00266
BG00364
BG00467
BG005296
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00056.2± 9.3
BG00156.8± 9.0
BG00254.5± 10.1
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00015
BG00129
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
American Indian or Alaska Native
Title
Measurements
BG0000
BG0010
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Hispanic
Title
Measurements
BG00015
BG00119
BG002
BMI
Mean
Standard Deviation
kg/m^2
Title
Denominators
Categories
Title
Measurements
BG00032.07± 4.41
BG00133.67± 5.37
BG002
Baseline HbA1c
Mean
Standard Deviation
Percentage of HbA1c
Title
Denominators
Categories
Title
Measurements
BG0008.04± 0.86
BG0017.97± 0.88
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Change From Baseline in HbA1c to 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.
Analysis was performed on Intent-to-treat (ITT) population which included all randomized participants, irrespective of compliance with the study protocol and procedures.
Posted
Least Squares Mean
Standard Error
percentage of HbA1c
Baseline, Week 26
ID
Title
Description
OG000
Placebo
Placebo (for SAR425899) SC injection QD from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
OG001
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).
OG002
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).
OG003
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).
OG004
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).
Units
Counts
Participants
OG00033
OG00166
OG00266
OG003
Title
Denominators
Categories
Title
Measurements
OG000-0.663± 0.169
OG001-1.517± 0.137
OG002-1.618± 0.133
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
OG002
OG003
Analysis was performed using analysis of covariance (ANCOVA) model with treatment groups, randomization strata of screening HbA1c value (<8, >=8 %), randomization strata of Visit 4 (Day 1) BMI (<35.0 kg/m^2, >=35.0 kg/m^2), and country as fixed effects and baseline HbA1c as a covariate. Overall 1st trend test based on a contrast with coefficients of +3, +1, -1, -3 and 0 for SAR425899 0.20 mg, 0.16 mg, 0.12 mg, placebo and liraglutide. Here it is test 1 of testing order.
ANCOVA
1st trend test
< 0.0001
Hierarchical testing procedure continued only, if the previous comparison was statistically significant. Threshold for significance at 0.05 level.
Secondary
Mean Change From Baseline in Body Weight to 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.
Analysis was performed on ITT population.
Posted
Least Squares Mean
Standard Error
Kg
Baseline, Week 26
ID
Title
Description
OG000
Placebo
Placebo (for SAR425899) SC injection QD from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
OG001
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).
OG002
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).
OG003
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).
Secondary
Percentage of Participants Reached HbA1c Target of <6.5% or <7% at 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.
Analysis was performed on ITT population.
Posted
Number
percentage of participants
Week 26
ID
Title
Description
OG000
Placebo
Placebo (for SAR425899) SC injection QD from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
OG001
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).
OG002
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).
OG003
SAR425899 0.20 mg
Secondary
Percentage of Participants Achieving >=5% or >=10% Body Weight Loss at 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.
Analysis was performed on ITT population.
Posted
Number
percentage of participants
Week 26
ID
Title
Description
OG000
Placebo
Placebo (for SAR425899) SC injection QD from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
OG001
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).
OG002
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).
OG003
SAR425899 0.20 mg
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) to 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.
Analysis was performed on ITT population.
Posted
Least Squares Mean
Standard Error
mmol/L
Baseline, Week 26
ID
Title
Description
OG000
Placebo
Placebo (for SAR425899) SC injection QD from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
OG001
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).
OG002
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).
OG003
SAR425899 0.20 mg
Secondary
Change From Baseline in Average 7 Point Self-Monitoring Plasma Glucose (SMPG) to 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.
Analysis was performed on ITT population. Overall number of participants analyzed = participants with at least 1 baseline and 1 post-baseline SMPG assessment during 26 week treatment period.
Posted
Mean
Standard Deviation
mmol/L
Baseline, Week 26
ID
Title
Description
OG000
Placebo
Placebo (for SAR425899) SC injection QD from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
OG001
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).
OG002
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).
Secondary
Percentage of Participants Requiring Rescue Therapy
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.
Analysis was performed on ITT population.
Posted
Number
percentage of participants
Baseline up to 26 weeks
ID
Title
Description
OG000
Placebo
Placebo (for SAR425899) SC injection QD from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
OG001
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).
OG002
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).
Secondary
Change From Baseline in Beta-Cell Function to 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.
Analysis was performed on ITT population.
Posted
Least Squares Mean
Standard Error
percentage of normal beta cells function
Baseline, Week 26
ID
Title
Description
OG000
Placebo
Placebo (for SAR425899) SC injection QD from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
OG001
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).
OG002
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).
OG003
Secondary
Change From Baseline in Insulin Resistance to 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.
Analysis was performed on ITT population.
Posted
Least Squares Mean
Standard Error
HOMA-IR Index
Baseline, Week 26
ID
Title
Description
OG000
Placebo
Placebo (for SAR425899) SC injection QD from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
OG001
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).
OG002
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).
OG003
SAR425899 0.20 mg
Secondary
Change From Baseline in Pharmacodynamic Biomarkers to Week 26 - Waist and Hip Circumferences
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.
Analysis was performed on ITT population.
Posted
Mean
Standard Error
cm
Baseline,Week 26
ID
Title
Description
OG000
Placebo
Placebo (for SAR425899) SC injection QD from Week 1 to Week 26, matching 3 SAR425899 dose levels of 0.12 mg, 0.16 mg and 0.20 mg.
OG001
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).
OG002
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).
Time Frame
All Adverse Events (AEs) were collected from signature of the informed consent form until 3 days after last treatment administration (Day 185).
Description
Reported AEs were treatment-emergent AEs that is AEs that developed/worsened or became serious during the 26-week'treatment period' (Treatment period was defined as time from the first injection of IMP up to last injection of IMP + 3 days). AE data was planned to be reported based on the dose received starting at Week 8 when adjustment of dose was not allowed (or randomized treatment arm if participant discontinued before Week 8).
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
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.
0
33
0
33
10
33
EG001
SAR425899 0.06 mg
Participants who were originally randomized to SAR425899 treatment groups and received 0.06 mg QD at Week 8.
0
18
2
18
18
18
EG002
SAR425899 0.12 mg
Participants 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
EG003
SAR425899 0.16 mg
Participants 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
EG004
SAR425899 0.20 mg
Participants 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
EG005
Liraglutide
Participants 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
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Sinus Tachycardia
Cardiac disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected72 at risk
EG0030 events0 affected59 at risk
EG0040 events0 affected47 at risk
EG0051 events1 affected67 at risk
Pancreatic Cyst
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Pancreatitis Chronic
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Cholecystitis Acute
Hepatobiliary disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Cellulitis Staphylococcal
Infections and infestations
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected72 at risk
EG003
Pneumonia
Infections and infestations
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Urinary Tract Infection
Infections and infestations
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Metastases To Adrenals
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Pancreatic Carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected72 at risk
EG003
Rectal Adenocarcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Hypoglycaemic Unconsciousness
Nervous system disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Loss Of Consciousness
Nervous system disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Hypertensive Crisis
Vascular disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0010 events0 affected18 at risk
EG0021 events1 affected72 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Splenomegaly
Blood and lymphatic system disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG0030 events0 affected59 at risk
EG0040 events0 affected47 at risk
EG0050 events0 affected67 at risk
Arteriosclerosis Coronary Artery
Cardiac disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Cardiac Failure Chronic
Cardiac disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Abdominal Discomfort
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0021 events1 affected72 at risk
EG003
Abdominal Distension
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0012 events2 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Abdominal Pain
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0002 events1 affected33 at risk
EG0011 events1 affected18 at risk
EG0021 events1 affected72 at risk
EG003
Abdominal Pain Upper
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0023 events3 affected72 at risk
EG003
Chronic Gastritis
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Constipation
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0010 events0 affected18 at risk
EG0025 events5 affected72 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0002 events2 affected33 at risk
EG00110 events7 affected18 at risk
EG00223 events15 affected72 at risk
EG003
Duodenitis
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0018 events6 affected18 at risk
EG00214 events13 affected72 at risk
EG003
Eructation
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0013 events2 affected18 at risk
EG0021 events1 affected72 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0024 events4 affected72 at risk
EG003
Gastrooesophageal Reflux Disease
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0013 events3 affected18 at risk
EG0022 events2 affected72 at risk
EG003
Gingival Pain
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Irritable Bowel Syndrome
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Nausea
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0008 events5 affected33 at risk
EG00122 events13 affected18 at risk
EG00245 events33 affected72 at risk
EG003
Pyloric Sphincter Insufficiency
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDra 20.1
Systematic Assessment
EG0002 events2 affected33 at risk
EG00117 events10 affected18 at risk
EG00232 events21 affected72 at risk
EG003
Asthenia
General disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0021 events1 affected72 at risk
EG003
Fatigue
General disorders
MedDra 20.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0011 events1 affected18 at risk
EG0021 events1 affected72 at risk
EG003
Injection Site Pain
General disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Injection Site Reaction
General disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0021 events1 affected72 at risk
EG003
Pyrexia
General disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Hepatic Steatosis
Hepatobiliary disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Hypersensitivity
Immune system disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Herpes Zoster
Infections and infestations
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Upper Respiratory Tract Infection
Infections and infestations
MedDra 20.1
Systematic Assessment
EG0002 events2 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Ligament Sprain
Injury, poisoning and procedural complications
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Alanine Aminotransferase Increased
Investigations
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Blood Creatinine Increased
Investigations
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Lipase Increased
Investigations
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0022 events1 affected72 at risk
EG003
Weight Decreased
Investigations
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0012 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Decreased Appetite
Metabolism and nutrition disorders
MedDra 20.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0013 events2 affected18 at risk
EG0024 events4 affected72 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Neck Pain
Musculoskeletal and connective tissue disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Dizziness
Nervous system disorders
MedDra 20.1
Systematic Assessment
EG0002 events2 affected33 at risk
EG0010 events0 affected18 at risk
EG0024 events4 affected72 at risk
EG003
Headache
Nervous system disorders
MedDra 20.1
Systematic Assessment
EG0001 events1 affected33 at risk
EG0014 events3 affected18 at risk
EG0025 events5 affected72 at risk
EG003
Aortic Arteriosclerosis
Vascular disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Hot Flush
Vascular disorders
MedDra 20.1
Systematic Assessment
EG0000 events0 affected33 at risk
EG0011 events1 affected18 at risk
EG0020 events0 affected72 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Hormones, Hormone Substitutes, and Hormone Antagonists
D001645
Biguanides
D006146
Guanidines
D000578
Amidines
D009930
Organic Chemicals
Browse Leaves
Not provided
Browse Branches
Not provided
1 subjects
3 subjects
55.0
± 10.4
BG00456.1± 11.4
BG00555.6± 10.2
35
BG00328
BG00436
BG005143
Male
BG00018
BG00137
BG00231
BG00336
BG00431
BG005153
0
BG0030
BG0041
BG0051
Asian/Oriental
Title
Measurements
BG0000
BG0011
BG0021
BG0032
BG0041
BG0055
Black
Title
Measurements
BG0002
BG0016
BG0026
BG0032
BG0044
BG00520
White
Title
Measurements
BG00031
BG00159
BG00259
BG00359
BG00461
BG005269
Other
Title
Measurements
BG0000
BG0010
BG0020
BG0031
BG0040
BG0051
25
BG00328
BG00413
BG005100
Non Hispanic
Title
Measurements
BG00018
BG00147
BG00241
BG00336
BG00454
BG005196
34.23
± 4.68
BG00333.63± 4.35
BG00434.23± 5.51
BG00533.74± 4.96
7.99
± 0.85
BG0038.14± 0.94
BG0048.11± 0.86
BG0058.05± 0.88
64
OG00467
-1.562
± 0.131
OG004-1.312± 0.118
Other
The overall Type 1 error for multiple comparisons of the HbA1c and body weight was controlled by a Hierarchical testing procedure. Testing was performed in following sequence: 1. 1st trend test for HbA1c, 2. 1st trend test for body weight, 3. 2nd trend test for HbA1c, 4. 2nd trend test for body weight, 5. 3rd trend test for HbA1c, 6. 3rd trend test for body weight.
OG000
OG002
Analysis was performed using ANCOVA model with treatment groups, randomization strata of screening HbA1c value (<8, >=8 %), randomization strata of Visit 4 (Day 1) BMI (<35.0 kg/m^2, >=35.0 kg/m^2), and country as fixed effects and baseline HbA1c as a covariate. Second Trend test based on a contrast with coefficients of 0, +1, 0, -1 and 0 for SAR425899 0.20 mg, 0.16 mg, 0.12 mg, placebo and liraglutide, respectively. Here, it is test no. 3 of hierarchical testing sequence.
ANCOVA
2nd Trend test
< 0.0001
Threshold for significance at 0.05 level.
LS Mean difference
-0.956
Standard Error of the Mean
0.206
2-Sided
95
-1.359
-0.552
Other
Hierarchical testing procedure continued only, if the previous comparison was statistically significant.
OG000
OG001
Analysis was performed using ANCOVA model with treatment groups, randomization strata of screening HbA1c value (<8, >=8 %), randomization strata of Visit 4 (Day 1) BMI (<35.0 kg/m^2, >=35.0 kg/m^2), and country as fixed effects and baseline HbA1c as a covariate. Third Trend test based on a contrast with coefficients of 0, 0, +1, -1 and 0 for SAR425899 0.20 mg, 0.16 mg, 0.12 mg, placebo and liraglutide, respectively. Here, it is test no. 5 of hierarchical testing sequence.
ANCOVA
3rd Trend test
< 0.0001
Threshold for significance at 0.05 level.
LS Mean difference
-0.854
Standard Error of the Mean
0.209
2-Sided
95
-1.264
-0.444
Other
Hierarchical testing procedure continued only, if the previous comparison was statistically significant.
OG004
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).
Units
Counts
Participants
OG00033
OG00166
OG00266
OG00364
OG00467
Title
Denominators
Categories
Title
Measurements
OG000-1.759± 0.734
OG001-4.276± 0.564
OG002-5.330± 0.549
OG003-4.407± 0.559
OG004-4.590± 0.521
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
OG002
OG003
Placebo, SAR425899 0.12,0.16,0.20 mg: Analysis was performed using ANCOVA model with treatment groups, randomization strata of screening HbA1c value (<8, >=8 %), randomization strata of Day 1 BMI (<35.0 kg/m^2, >=35.0 kg/m^2), and country as fixed effects and baseline body weight as a covariate. Here, it is test no. 2 of hierarchical testing sequence.
ANCOVA
1st Trend test
0.0012
Threshold for significance at 0.05 level.
Other
Hierarchical testing procedure continued only, if the previous comparison was statistically significant.
OG000
OG002
SAR425899 0.16 mg vs Placebo: Analysis was performed using ANCOVA model with treatment groups, randomization strata of screening HbA1c value (<8, >=8 %), randomization strata of Day 1 BMI (<35.0 kg/m^2, >=35.0 kg/m^2), and country as fixed effects and baseline body weight as a covariate. Here, it is test no. 4 of hierarchical testing sequence.
ANCOVA
2nd Trend test
< 0.0001
Threshold for significance at 0.05 level.
LS Mean difference
-3.57
Standard Error of the Mean
0.887
2-Sided
95
-5.309
-1.832
Other
Hierarchical testing procedure continued only, if the previous comparison was statistically significant
OG000
OG001
3rd Trend Test: SAR425899 0.12 mg vs Placebo: Analysis was performed using ANCOVA model with treatment groups, randomization strata of screening HbA1c value (<8, >=8 %), randomization strata of Day 1 BMI (<35.0 kg/m^2, >=35.0 kg/m^2), and country as fixed effects and baseline body weight as a covariate. Here, it is test no. 6 of hierarchical testing sequence.
ANCOVA
3rd Trend test
0.0047
Threshold for significance at 0.05 level.
LS Mean difference
-2.517
Standard Error of the Mean
0.891
2-Sided
95
-4.264
-0.77
Other
Hierarchical testing procedure continued only, if the previous comparison was statistically significant.
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).
OG004
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).
Units
Counts
Participants
OG00033
OG00166
OG00266
OG00364
OG00467
Title
Denominators
Categories
Participants with HbA1c Target of <6.5%
Title
Measurements
OG00012.1
OG00147.0
OG00251.5
OG00348.4
OG00444.8
Participants with HbA1c Target of <7%
Title
Measurements
OG00036.4
OG00166.7
OG00268.2
OG003
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).
OG004
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).
Units
Counts
Participants
OG00033
OG00166
OG00266
OG00364
OG00467
Title
Denominators
Categories
Participants Achieving >=5% Body Weight Loss
Title
Measurements
OG0003.0
OG00133.3
OG00245.5
OG00335.9
OG00440.3
Participants Achieving >=10% Body Weight Loss
Title
Measurements
OG0000.0
OG00112.1
OG00213.6
OG003
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).
OG004
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).
Units
Counts
Participants
OG00033
OG00166
OG00266
OG00364
OG00467
Title
Denominators
Categories
Title
Measurements
OG000-0.931± 0.394
OG001-2.408± 0.308
OG002-2.548± 0.301
OG003-2.318± 0.312
OG004-2.124± 0.280
OG003
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).
OG004
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).
Units
Counts
Participants
OG00021
OG00140
OG00243
OG00344
OG00449
Title
Denominators
Categories
Title
Measurements
OG000-1.82± 3.11
OG001-2.86± 2.62
OG002-2.63± 2.70
OG003-2.49± 3.18
OG004-2.21± 2.23
OG003
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).
OG004
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).
Units
Counts
Participants
OG00033
OG00166
OG00266
OG00364
OG00467
Title
Denominators
Categories
Title
Measurements
OG00018.2
OG0010.0
OG0021.5
OG0033.1
OG0046.0
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).
OG004
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).
Units
Counts
Participants
OG00033
OG00166
OG00266
OG00364
OG00467
Title
Denominators
Categories
Title
Measurements
OG00015.025± 19.785
OG00126.768± 15.833
OG00231.122± 16.467
OG00317.932± 14.397
OG00427.263± 13.234
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).
OG004
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).
Units
Counts
Participants
OG00033
OG00166
OG00266
OG00364
OG00467
Title
Denominators
Categories
Title
Measurements
OG000-1.315± 0.865
OG001-1.244± 0.670
OG002-2.233± 0.664
OG003-2.324± 0.649
OG004-1.405± 0.613
OG003
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).
OG004
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).