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Comparison of SAR342434 to Humalog as the Rapid Acting Insulin in Adult Patients With Type 2 Diabetes Mellitus Also Using Insulin Glargine

Phase 3
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Drug: insulin glargine HOE901
Registration Number
NCT02294474
Lead Sponsor
Sanofi
Brief Summary

Primary Objective:

To demonstrate non-inferiority of SAR342434 versus Humalog in glycated hemoglobin A1c (HbA1c) change from baseline to Week 26 in participants with type 2 diabetes mellitus (T2DM) also using insulin glargine.

Secondary Objectives:

To assess the immunogenicity of SAR342434 and Humalog in terms of positive/negative status and antibody titers at baseline and during the course of the study; To assess the relationship of anti-insulin antibodies with efficacy and safety. To assess the efficacy of SAR342434 and Humalog on: proportion of participants reaching target HbA1c \<7.0% and \<=6.5%, fasting plasma glucose (FPG) and self-measured plasma glucose (SMPG) profiles, and insulin dose.

To assess safety of SAR342434 and Humalog.

Detailed Description

The study will consist of a: up to 2 weeks screening period, 26-week treatment period, and 1-day follow-up period.

The maximum study duration will then be 28 weeks per participant and a 1-day safety follow-up.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
505
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
HumalogHumalogHumalog 100 U/mL before meals intake on top of QD Insulin Glargine, up to Week 26.
SAR342434SAR342434SAR342434 100 Unit/mL (U/mL) before meals intake on top of once daily (QD) Insulin Glargine, up to Week 26.
Humaloginsulin glargine HOE901Humalog 100 U/mL before meals intake on top of QD Insulin Glargine, up to Week 26.
SAR342434insulin glargine HOE901SAR342434 100 Unit/mL (U/mL) before meals intake on top of once daily (QD) Insulin Glargine, up to Week 26.
Primary Outcome Measures
NameTimeMethod
Change in HbA1c From Baseline to Week 26Baseline, Week 26

Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Adjusted least square means and standard errors were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data, using all post-baseline HbA1c data available during the 6-month period and adequate contrasts at Week 26.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With HbA1c <7.0% and <=6.5% at Week 26Week 26

Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders.

Change in Mean 24-Hour Plasma Glucose Concentration From Baseline to Week 26Baseline, Week 26

The mean 24-hour plasma glucose concentration was calculated based on 7-point self-measured plasma glucose (SMPG) profiles with plasma glucose measurements before and 2-hours after each main meal and at bedtime. 7-point SMPGs were performed at least two times in a week before baseline, before visit Week 12 and before visit Week 26. Mean 24-hour plasma glucose concentration was calculated for each profile and then averaged across profiles performed in the week before a visit. Change in mean 24-hour plasma glucose concentration was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during 6-month period and adequate contrasts at Week 26.

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

Change in FPG was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM approach to account for missing data, using all post-baseline FPG data available during the 6-month period and adequate contrasts at Week 26.

Change in Post Prandial Glucose (PPG) Excursion From Baseline to Week 26Baseline, Week 26

Plasma glucose excursions were calculated at breakfast, lunch and dinner for each 7-point SMPG profile, as 2-hour postprandial glucose (PPG) minus plasma glucose value obtained 30 minutes prior to start of the meal. Values of plasma glucose excursions at each visit were then calculated as average across the profiles performed in the week before the visit. Change in PPG excursions was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during the 6-month period and adequate contrasts at Week 26.

Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia and Severe Hypoglycemia)First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Percentage of participants with at least one treatment emergent hypoglycemia reported at any time of the day were reported. Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=70 mg/dL (3.9 mmol/L). Hypoglycemic episodes with plasma glucose of 54 mg/dL (\<3.0 mmol/L) were also analyzed.

Percentage of Participants With Hypersensitivity Reactions and Injection Site ReactionsFirst dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Percentage of participants with hypersensitivity reactions and injection site reactions were reported.

Percentage of Participants With Treatment-Emergent Anti-insulin Antibodies (AIAs)First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Participants with treatment-emergent AIA (incidence) were reported (as participants with treatment-boosted or treatment-induced AIAs). Participants with treatment-induced AIAs were participants who developed AIA following IMP administration (participants with at least one positive AIA sample at any time during on-treatment period, in those participants without pre-existing AIA or with missing baseline sample). Participants with treatment-boosted AIAs were participants with pre-existing AIAs that were boosted to a significant higher titer following IMP administration (participants with at least one AIA sample with at least a 4-fold increase in titers compared to baseline value at any time during on-treatment period, in those participants with pre-existing AIA).

Trial Locations

Locations (103)

Investigational Site Number 840234

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Los Angeles, California, United States

Investigational Site Number 840242

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Port Charlotte, Florida, United States

Investigational Site Number 840216

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Lincoln, Nebraska, United States

Investigational Site Number 840221

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Columbus, Ohio, United States

Investigational Site Number 840201

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Dallas, Texas, United States

Investigational Site Number 840239

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Rockville, Maryland, United States

Investigational Site Number 348205

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Budapest, Hungary

Investigational Site Number 152204

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Santiago, Chile

Investigational Site Number 170203

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Armenia, Colombia

Investigational Site Number 642210

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Bacau, Romania

Investigational Site Number 348208

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Komárom, Hungary

Investigational Site Number 348210

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Nagykanizsa, Hungary

Investigational Site Number 840217

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Foley, Alabama, United States

Investigational Site Number 840237

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Muscle Shoals, Alabama, United States

Investigational Site Number 840212

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Little Rock, Arkansas, United States

Investigational Site Number 840241

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El Cajon, California, United States

Investigational Site Number 840248

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Arlington Heights, Illinois, United States

Investigational Site Number 380203

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Bologna, Italy

Investigational Site Number 642201

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Bucuresti, Romania

Investigational Site Number 643203

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St-Petersburg, Russian Federation

Investigational Site Number 792202

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Istanbul, Turkey

Investigational Site Number 840246

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Miami, Florida, United States

Investigational Site Number 840219

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Phoenix, Arizona, United States

Investigational Site Number 840227

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Phoenix, Arizona, United States

Investigational Site Number 840220

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Las Vegas, Nevada, United States

Investigational Site Number 840233

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Las Vegas, Nevada, United States

Investigational Site Number 840251

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Palm Springs, California, United States

Investigational Site Number 840238

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Fresno, California, United States

Investigational Site Number 840214

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Boynton Beach, Florida, United States

Investigational Site Number 840240

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Walnut Creek, California, United States

Investigational Site Number 840226

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New Port Richey, Florida, United States

Investigational Site Number 840206

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Palm Harbor, Florida, United States

Investigational Site Number 840225

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Fargo, North Dakota, United States

Investigational Site Number 840230

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Des Moines, Iowa, United States

Investigational Site Number 840208

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Chattanooga, Tennessee, United States

Investigational Site Number 032201

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Caba, Argentina

Investigational Site Number 032202

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Capital Federal, Argentina

Investigational Site Number 840255

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Dayton, Ohio, United States

Investigational Site Number 840215

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Jackson, Tennessee, United States

Investigational Site Number 032203

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Salta, Argentina

Investigational Site Number 152201

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Santiago, Chile

Investigational Site Number 840250

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Tipton, Pennsylvania, United States

Investigational Site Number 840243

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Uniontown, Pennsylvania, United States

Investigational Site Number 276202

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Neumünster, Germany

Investigational Site Number 032206

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Capital Federal, Argentina

Investigational Site Number 032205

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Ciudad Autonoma De Buenos Aire, Argentina

Investigational Site Number 152202

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Santiago, Chile

Investigational Site Number 348203

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Szolnok, Hungary

Investigational Site Number 840209

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Milwaukee, Wisconsin, United States

Investigational Site Number 276206

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Potsdam, Germany

Investigational Site Number 276201

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Berlin, Germany

Investigational Site Number 276205

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Stuttgart, Germany

Investigational Site Number 276204

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Heidelberg, Germany

Investigational Site Number 724201

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Barcelona, Spain

Investigational Site Number 380202

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Sesto San Giovanni, Italy

Investigational Site Number 276203

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Sulzbach-Rosenberg, Germany

Investigational Site Number 348204

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Debrecen, Hungary

Investigational Site Number 348209

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Sátoraljaújhely, Hungary

Investigational Site Number 642202

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Bucuresti, Romania

Investigational Site Number 380201

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Milano, Italy

Investigational Site Number 380204

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Roma, Italy

Investigational Site Number 410204

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Seoul, Korea, Republic of

Investigational Site Number 410201

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Wonju, Korea, Republic of

Investigational Site Number 410205

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Seoul, Korea, Republic of

Investigational Site Number 642206

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Cluj Napoca, Romania

Investigational Site Number 642204

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Deva, Romania

Investigational Site Number 642209

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Sibiu, Romania

Investigational Site Number 643202

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St-Petersburg, Russian Federation

Investigational Site Number 642205

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Oradea, Romania

Investigational Site Number 642207

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Targu Mures, Romania

Investigational Site Number 642208

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Targu Mures, Romania

Investigational Site Number 642203

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Timisoara, Romania

Investigational Site Number 643201

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Saint-Petersburg, Russian Federation

Investigational Site Number 643205

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Saratov, Russian Federation

Investigational Site Number 724202

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Palma De Mallorca, Spain

Investigational Site Number 643204

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St. Petersburg, Russian Federation

Investigational Site Number 792201

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Istanbul, Turkey

Investigational Site Number 792204

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Izmir, Turkey

Investigational Site Number 792203

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Izmir, Turkey

Investigational Site Number 724203

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Málaga, Spain

Investigational Site Number 840247

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Long Beach, California, United States

Investigational Site Number 840231

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Huntington Beach, California, United States

Investigational Site Number 840229

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Greenbrae, California, United States

Investigational Site Number 840249

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Santa Ana, California, United States

Investigational Site Number 840259

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Tustin, California, United States

Investigational Site Number 840235

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Northridge, California, United States

Investigational Site Number 840207

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Stockbridge, Georgia, United States

Investigational Site Number 840204

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Avon, Indiana, United States

Investigational Site Number 840257

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Evansville, Indiana, United States

Investigational Site Number 840232

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Greensboro, North Carolina, United States

Investigational Site Number 840203

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Austin, Texas, United States

Investigational Site Number 840211

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Morehead City, North Carolina, United States

Investigational Site Number 840228

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Morganton, North Carolina, United States

Investigational Site Number 840253

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Lawrenceville, Georgia, United States

Investigational Site Number 840205

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Ocoee, Florida, United States

Investigational Site Number 840223

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Temecula, California, United States

Investigational Site Number 348202

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Budapest, Hungary

Investigational Site Number 840222

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Renton, Washington, United States

Investigational Site Number 410202

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Seoul, Korea, Republic of

Investigational Site Number 840258

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Dallas, Texas, United States

Investigational Site Number 840245

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Chandler, Arizona, United States

Investigational Site Number 840224

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Linden, New Jersey, United States

Investigational Site Number 840236

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Troy, Michigan, United States

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