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

Type 2 Diabetes Mellitus Clinical Trial

— SORELLA2  

Official title:

Six-month, Randomized, Open-label, Parallel-group Comparison of the Insulin Analog SAR342434 to Humalog® in Adult Patients With Type 2 Diabetes Mellitus Also Using Insulin Glargine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02294474
• Other study ID #: EFC13403
• Secondary ID: 2014-002844-42U1
• Status: Completed
• Phase: Phase 3
• First received: November 14, 2014
• Last updated: December 20, 2017
• Start date: January 2015
• Est. completion date: February 2016

Study information

• Verified date: December 2017
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 505
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Participants with T2DM diagnosed for at least 12 months and treated with insulin glargine and Humalog®/Liprolog® or NovoLog®/NovoRapid® (at least 3 times daily, before each meal) in the 6 months prior to the screening visit.

• Signed written informed consent.

Exclusion criteria:

• At screening visit, age under legal age of adulthood.

• HbA1c <6.5% or >10.0% at screening.

• Diabetes other than T2DM.

• Pregnancy and lactation.

• Women of childbearing potential not protected by highly effective contraceptive method of birth control.

• Use of insulin pump in the 6 months before screening visit.

• Use of insulin other than insulin glargine and Humalog or NovoLog/NovoRapid in the 6 months prior to screening visit. Liprolog® is an European Union (EU) approved insulin lispro and is allowed in those countries where it is marketed.

• Use of Humalog/Liprolog or Novolog/NovoRapid less than 3 times daily, before each meal.

• Use of non-injectable peptides (eg, Glucagon-like peptide-1 (GLP-1) receptor-agonists or other peptides) in the 6 months prior to screening visit.

• Body mass index (BMI) >=40kg/m² at screening visit.

• Hospitalization for diabetic ketoacidosis in the last 6 months before screening visit.

• Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (eg, laser, surgical treatment, or injectable drugs) during the study period.

• The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• SAR342434
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 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
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.
• insulin glargine HOE901
Insulin glargine 100 U/mL injected QD subcutaneously consistent with the local label. Doses adjusted to achieve glycemic target for fasting, preprandial plasma glucose (SMPG) between 4.4 to 7.2 mmol/L (80 to 130 mg/dL) without hypoglycemia.

Locations

Country	Name	City	State
Argentina	Investigational Site Number 032201	Caba
Argentina	Investigational Site Number 032202	Capital Federal
Argentina	Investigational Site Number 032206	Capital Federal
Argentina	Investigational Site Number 032205	Ciudad Autonoma De Buenos Aire
Argentina	Investigational Site Number 032203	Salta
Chile	Investigational Site Number 152201	Santiago
Chile	Investigational Site Number 152202	Santiago
Chile	Investigational Site Number 152204	Santiago
Colombia	Investigational Site Number 170203	Armenia
Germany	Investigational Site Number 276201	Berlin
Germany	Investigational Site Number 276204	Heidelberg
Germany	Investigational Site Number 276202	Neumünster
Germany	Investigational Site Number 276206	Potsdam
Germany	Investigational Site Number 276205	Stuttgart
Germany	Investigational Site Number 276203	Sulzbach-Rosenberg
Hungary	Investigational Site Number 348202	Budapest
Hungary	Investigational Site Number 348205	Budapest
Hungary	Investigational Site Number 348204	Debrecen
Hungary	Investigational Site Number 348208	Komárom
Hungary	Investigational Site Number 348210	Nagykanizsa
Hungary	Investigational Site Number 348209	Sátoraljaújhely
Hungary	Investigational Site Number 348203	Szolnok
Italy	Investigational Site Number 380203	Bologna
Italy	Investigational Site Number 380201	Milano
Italy	Investigational Site Number 380204	Roma
Italy	Investigational Site Number 380202	Sesto San Giovanni
Korea, Republic of	Investigational Site Number 410202	Seoul
Korea, Republic of	Investigational Site Number 410204	Seoul
Korea, Republic of	Investigational Site Number 410205	Seoul
Korea, Republic of	Investigational Site Number 410201	Wonju
Romania	Investigational Site Number 642210	Bacau
Romania	Investigational Site Number 642201	Bucuresti
Romania	Investigational Site Number 642202	Bucuresti
Romania	Investigational Site Number 642206	Cluj Napoca
Romania	Investigational Site Number 642204	Deva
Romania	Investigational Site Number 642205	Oradea
Romania	Investigational Site Number 642209	Sibiu
Romania	Investigational Site Number 642207	Targu Mures
Romania	Investigational Site Number 642208	Targu Mures
Romania	Investigational Site Number 642203	Timisoara
Russian Federation	Investigational Site Number 643201	Saint-Petersburg
Russian Federation	Investigational Site Number 643205	Saratov
Russian Federation	Investigational Site Number 643202	St-Petersburg
Russian Federation	Investigational Site Number 643203	St-Petersburg
Russian Federation	Investigational Site Number 643204	St. Petersburg
Spain	Investigational Site Number 724201	Barcelona
Spain	Investigational Site Number 724203	Málaga
Spain	Investigational Site Number 724202	Palma De Mallorca
Turkey	Investigational Site Number 792201	Istanbul
Turkey	Investigational Site Number 792202	Istanbul
Turkey	Investigational Site Number 792203	Izmir
Turkey	Investigational Site Number 792204	Izmir
United States	Investigational Site Number 840248	Arlington Heights	Illinois
United States	Investigational Site Number 840203	Austin	Texas
United States	Investigational Site Number 840204	Avon	Indiana
United States	Investigational Site Number 840214	Boynton Beach	Florida
United States	Investigational Site Number 840245	Chandler	Arizona
United States	Investigational Site Number 840208	Chattanooga	Tennessee
United States	Investigational Site Number 840221	Columbus	Ohio
United States	Investigational Site Number 840201	Dallas	Texas
United States	Investigational Site Number 840258	Dallas	Texas
United States	Investigational Site Number 840255	Dayton	Ohio
United States	Investigational Site Number 840230	Des Moines	Iowa
United States	Investigational Site Number 840241	El Cajon	California
United States	Investigational Site Number 840257	Evansville	Indiana
United States	Investigational Site Number 840225	Fargo	North Dakota
United States	Investigational Site Number 840217	Foley	Alabama
United States	Investigational Site Number 840238	Fresno	California
United States	Investigational Site Number 840229	Greenbrae	California
United States	Investigational Site Number 840232	Greensboro	North Carolina
United States	Investigational Site Number 840231	Huntington Beach	California
United States	Investigational Site Number 840215	Jackson	Tennessee
United States	Investigational Site Number 840220	Las Vegas	Nevada
United States	Investigational Site Number 840233	Las Vegas	Nevada
United States	Investigational Site Number 840253	Lawrenceville	Georgia
United States	Investigational Site Number 840216	Lincoln	Nebraska
United States	Investigational Site Number 840224	Linden	New Jersey
United States	Investigational Site Number 840212	Little Rock	Arkansas
United States	Investigational Site Number 840247	Long Beach	California
United States	Investigational Site Number 840234	Los Angeles	California
United States	Investigational Site Number 840246	Miami	Florida
United States	Investigational Site Number 840209	Milwaukee	Wisconsin
United States	Investigational Site Number 840211	Morehead City	North Carolina
United States	Investigational Site Number 840228	Morganton	North Carolina
United States	Investigational Site Number 840237	Muscle Shoals	Alabama
United States	Investigational Site Number 840226	New Port Richey	Florida
United States	Investigational Site Number 840235	Northridge	California
United States	Investigational Site Number 840205	Ocoee	Florida
United States	Investigational Site Number 840206	Palm Harbor	Florida
United States	Investigational Site Number 840251	Palm Springs	California
United States	Investigational Site Number 840219	Phoenix	Arizona
United States	Investigational Site Number 840227	Phoenix	Arizona
United States	Investigational Site Number 840242	Port Charlotte	Florida
United States	Investigational Site Number 840222	Renton	Washington
United States	Investigational Site Number 840239	Rockville	Maryland
United States	Investigational Site Number 840249	Santa Ana	California
United States	Investigational Site Number 840207	Stockbridge	Georgia
United States	Investigational Site Number 840223	Temecula	California
United States	Investigational Site Number 840250	Tipton	Pennsylvania
United States	Investigational Site Number 840236	Troy	Michigan
United States	Investigational Site Number 840259	Tustin	California
United States	Investigational Site Number 840243	Uniontown	Pennsylvania
United States	Investigational Site Number 840240	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Colombia,  Germany,  Hungary,  Italy,  Korea, Republic of,  Romania,  Russian Federation,  Spain,  Turkey, 

References & Publications (1)

Derwahl KM, Bailey TS, Wernicke-Panten K, Ping L, Pierre S. Efficacy and Safety of Biosimilar SAR342434 Insulin Lispro in Adults with Type 2 Diabetes, Also Using Insulin Glargine: SORELLA 2 Study. Diabetes Technol Ther. 2018 Jan;20(1):49-58. doi: 10.1089/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Daily Insulin Dose From Baseline to Week 26	Change in daily insulin dose (basal, mealtime and total) was calculated by subtracting baseline value from Week 26 value.	Baseline, Week 26
Primary	Change in HbA1c From Baseline to 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.	Baseline, Week 26
Secondary	Percentage of Participants With HbA1c <7.0% and <=6.5% at Week 26	Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders.	Week 26
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline to 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.	Baseline, Week 26
Secondary	Change in Mean 24-Hour Plasma Glucose Concentration From Baseline to 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.	Baseline, Week 26
Secondary	Change in Post Prandial Glucose (PPG) Excursion From Baseline to 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.	Baseline, Week 26
Secondary	Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia and Severe Hypoglycemia)	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.	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)
Secondary	Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions	Percentage of participants with hypersensitivity reactions and injection site reactions were reported.	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)
Secondary	Percentage of Participants With Treatment-Emergent Anti-insulin Antibodies (AIAs)	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).	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)