EFC13403

Sanofi aventis recherche & développement

1 avenue Pierre Brossolette, Chilly-­Mazarin, France, 91380

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

No

No

No

Final

11 Apr 2016

No

Yes

16 Feb 2016

No

To demonstrate the non-inferiority of SAR342434 versus Humalog in terms of changes in glycated hemoglobin (HbA1c) from baseline to Week 26 in subjects with type 2 diabetes mellitus also using Lantus.

Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.

14 Jan 2015

No

No

Romania: 40

Spain: 12

Germany: 36

Hungary: 45

Italy: 21

Argentina: 37

Chile: 14

Colombia: 1

Korea, Republic of: 17

Russian Federation: 30

Turkey: 10

United States: 242

505

154

0

0

0

0

0

0

281

222

2

Overall Study (overall period)

Randomised - controlled

Yes

SAR342434

Solution for injection

Subcutaneous use

SAR342434 100 U/mL (dose range of 1 Unit to 80 Units) self-administered by subcutaneous (SC) injection, immediately (within 5-10 minutes) before meals intake. Dose adjusted to achieve a 2-hour post prandial glucose (PPG) in range of 6.7 to 8.9 mmol/L (120 to 160 mg/dL) while avoiding hypoglycemia.

Humalog

Insulin Lispro

Solution for injection

Subcutaneous use

Humalog 100 U/ml (dose range of 1 unit to 60 units) self-administered by SC injection, immediately (within 5-10 minutes) before meals intake. Dose adjusted to achieve a 2-hour PPG in range of 6.7 to 8.9 mmol/L (120 to 160 mg/dL) while avoiding hypoglycemia.

SAR342434

Humalog

SAR342434

Humalog

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. Analysis was performed on intent-to-treat (ITT) population that included all randomized subjects, irrespective of compliance with the study protocol and procedures. Here, number of subjects analyzed = subjects with at least one post-baseline HbA1c assessment during the 6-month study period.

Primary

Baseline, Week 26

Analysis was performed using a MMRM approach with treatment groups, randomization strata, visit (Week 12, Week 26) and treatment-by-visit interaction as fixed categorical effects and baseline HbA1c value and baseline HbA1c value-by-visit interaction as continuous fixed covariates. An unstructured correlation matrix was used to model within-subject errors.

SAR342434 v Humalog

485

Pre-specified

-0.07

2-sided

Standard error of the mean

0.072

Subjects who had no available assessment for HbA1c at Week 26 were considered as non-responders. Analysis was performed on ITT population.

Secondary

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. Analysis was performed on ITT population. Here, number of subjects analyzed = subjects with at least one post-baseline FPG assessment during the 6-months study period.

Secondary

Baseline, 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. Analysis was performed on ITT population. Here, number of subjects analyzed=subjects with at least one post-baseline mean 24-hour plasma glucose concentration assessment during 6-month study period.

Secondary

Baseline, 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. Analysis was performed on ITT population. Here, 'n' signifies number of subjects with available data for specified category.

Secondary

Baseline, Week 26

Percentage of subjects with at least one treatment emergent hypoglycemia reported at any time of the day were reported. Severe hypoglycemia was an event in which the subject required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available. 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. Analysis was performed on safety population that included all subjects randomized and exposed to at least 1 dose of investigational medicinal product (IMP) (SAR342434 or Humalog), regardless of the amount of treatment administered.

Secondary

First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Analysis was performed on safety population that included all subjects randomized and exposed to at least 1 dose of IMP (SAR342434 or Humalog), regardless of the amount of treatment administered.

Secondary

First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Subjects with treatment-emergent AIA (incidence) were reported (as subjects with treatment-boosted or treatment-induced AIAs). Subjects with treatment-induced AIAs were subjects who developed AIA following IMP administration (subjects with at least one positive AIA sample at any time during on-treatment period, in those subjects without pre-existing AIA or with missing baseline sample). Subjects with treatment-boosted AIAs were subjects with pre-existing AIAs that were boosted significant higher titer following IMP administration (subjects 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 subjects with pre-existing AIA). Analysis was performed on anti-insulin antibody population that included all subjects from the safety population with at least one AIA sample available for analysis during the 6-months on-treatment period.

Secondary

First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Change in daily insulin dose (basal, mealtime and total) was calculated by subtracting baseline value from Week 26 value. Analysis was performed on safety population. Here, 'n' signifies number of subjects with available data for specified category.

Other pre-specified

Baseline, Week 26

All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 183) regardless of seriousness or relationship to investigational product.

Reported adverse events are treatment-emergent adverse events that is AEs that developed, worsened or became serious during the ‘on treatment period’ (time from first injection of IMP up to 1 day after the last injection of IMP).

18.1

SAR342434

Humalog