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Comparison of SAR342434 to Humalog as the Rapid Acting Insulin in Adult Patients With Type 1 Diabetes Mellitus Also Using Insulin Glargine

Phase 3
Completed
Conditions
Type 1 Diabetes Mellitus
Interventions
Drug: Insulin glargine HOE901
Registration Number
NCT02273180
Lead Sponsor
Sanofi
Brief Summary

Primary Objective:

To demonstrate non-inferiority of SAR342434 versus Humalog in glycated haemoglobin A1c (HbA1c) change from baseline to Week 26 in participants with type 1 diabetes mellitus (T1DM) 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 including during the safety extension.

To assess the efficacy of SAR342434 and Humalog in terms of proportion of participants reaching target HbA1c (\<7%), Fasting plasma glucose (FPG), self-measured plasma glucose (SMPG) profiles, and insulin dose.

To assess safety of SAR342434 and Humalog.

Detailed Description

The study consisted of a:

* Up to 2 weeks screening period

* 26-week treatment period

* 26-week comparative safety extension period

* 1-day follow-up period

* The maximum study duration would be 54 weeks per participant and a 1-day safety follow-up

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
507
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SAR342434SAR342434SAR342434 before meals intake on top of once daily (QD) Insulin Glargine, up to Week 52.
SAR342434Insulin glargine HOE901SAR342434 before meals intake on top of once daily (QD) Insulin Glargine, up to Week 52.
HumalogInsulin glargine HOE901Humalog before meals intake on top of QD Insulin Glargine, up to Week 52.
HumalogHumalogHumalog before meals intake on top of QD Insulin Glargine, up to Week 52.
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 main 6-month period and adequate contrasts at Week 26.

Secondary Outcome Measures
NameTimeMethod
Change in Mean 24-Hour Plasma Glucose Concentration From Baseline to Week 26Baseline, Week 26

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. Mean 24-hour plasma glucose concentration was calculated for each profile and then averaged across profiles performed in 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 the main 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 main 6-month period and adequate contrasts at Week 26.

Change in Post Prandial Plasma 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 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 main 6-month period and adequate contrasts at Week 26.

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: 400 days)

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

Percentage of Participants With HbA1c <7.0% at Week 26Week 26

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

Number of Hypoglycemia Events (Any Hypoglycemia, Documented Symptomatic Hypoglycemia and Severe Hypoglycemia) Per Participant-YearFirst dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 400 days)

Number of treatment-emergent hypoglycemia events per participant-year of exposure 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 Treatment Emergent Anti-insulin Antibodies (AIAs)First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 400 days)

Participants with treatment-emergent AIA (incidence) were reported (as participants with treatment-boosted or treatment-induced AIAs). Participants with treatment-induced AIAs were those 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 those 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 (89)

Investigational Site Number 840049

🇺🇸

Tucson, Arizona, United States

Investigational Site Number 840016

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Bell Gardens, California, United States

Investigational Site Number 840048

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Chula Vista, California, United States

Investigational Site Number 840046

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Concord, California, United States

Investigational Site Number 840039

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Fresno, California, United States

Investigational Site Number 840028

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La Jolla, California, United States

Investigational Site Number 840022

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Ventura, California, United States

Investigational Site Number 840003

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Denver, Colorado, United States

Investigational Site Number 840037

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Denver, Colorado, United States

Investigational Site Number 840005

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Bradenton, Florida, United States

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Investigational Site Number 840049
🇺🇸Tucson, Arizona, United States

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