Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Comparison of SAR341402 to NovoLog/NovoRapid in Adult Patients With Diabetes Mellitus Also Using Insulin Glargine (GEMELLI 1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03211858
Recruitment Status : Completed
First Posted : July 7, 2017
Results First Posted : August 8, 2019
Last Update Posted : August 8, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To demonstrate non-inferiority of SAR341402 versus NovoLog/NovoRapid in glycated hemoglobin A1c (HbA1c) change from baseline to Week 26 in participants with type 1 or type 2 diabetes mellitus (T1DM or T2DM) also using Lantus®.

Secondary Objectives:

  • To assess the immunogenicity of SAR341402 and NovoLog/NovoRapid in terms of positive/negative status and anti-insulin antibody (AIA) titers during the course of the study.
  • To assess the relationship of AIAs with efficacy and safety.
  • To assess the efficacy of SAR341402 and NovoLog/NovoRapid in terms of proportion of participants reaching HbA1c <7.0% and change in HbA1c, fasting plasma glucose (FPG), and self-measured plasma glucose (SMPG) profiles from baseline to Week 26 and Week 52 (only Week 52 for HbA1c).
  • To assess safety of SAR341402 and NovoLog/NovoRapid.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus-Type 2 Diabetes Mellitus Drug: Insulin Lispro Drug: Novolog/Novorapid Drug: Insulin glargine (HOE901) Phase 3

Detailed Description:
The study consisted of a 2-week screening period, a 26-week treatment period, a 26-week comparative safety extension period, and a 1-day follow-up period. The maximum study duration was 54 weeks per participant and a 1 day safety follow-up.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 597 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Six-month, Randomized, Open-label, Parallel-group Comparison of SAR341402 to NovoLog®/NovoRapid® in Adult Patients With Diabetes Also Using Insulin Glargine, With a 6-month Safety Extension Period
Actual Study Start Date : August 2, 2017
Actual Primary Completion Date : July 16, 2018
Actual Study Completion Date : January 12, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SAR341402
SAR341402 subcutaneous (SC), before meals intake on top of once daily (QD) Insulin Glargine, up to Week 26.
Drug: Insulin Lispro
SAR341402 100 units per milliliters (U/mL) (dose range of 1 unit to 80 units) self-administered by SC injection, immediately (within 5-10 minutes) before meal intake. Dose adjusted to achieve a 2 hour postprandial plasma glucose (PPG < 10 millimolar/Liter [mmol/L] [<180 milligram/deciLiter {mg/dL}]) while avoiding hypoglycemia.

Drug: 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 between 4.4 to 7.2 mmol/L (80 to 130 mg/dL) without hypoglycemia.
Other Name: Lantus

Active Comparator: NovoLog/NovoRapid
NovoLog/NovoRapid SC, before meals intake on top of QD Insulin Glargine, up to Week 26.
Drug: Novolog/Novorapid
NovoLog/NovoRapid 100 U/mL (dose range of 1 unit to 60 units) self-administered by SC injection, immediately (within 5-10 minutes) before meal intake. Dose adjusted to achieve a 2 hour postprandial plasma glucose (PPG < 10 mmol/L [<180 mg/dL]) while avoiding hypoglycemia.
Other Name: Insulin aspart

Drug: 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 between 4.4 to 7.2 mmol/L (80 to 130 mg/dL) without hypoglycemia.
Other Name: Lantus




Primary Outcome Measures :
  1. Change in Glycated Hemoglobin A1c From Baseline to Week 26 [ Time Frame: Baseline to Week 26 ]
    All values up to Week 26 were taken into account in the analysis, regardless of adherence to treatment. Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Missing changes at Week 26 were imputed using a retrieved dropout multiple imputation method (separately for participants who prematurely discontinued or completed treatment). Adjusted least square (LS) means and standard errors (SE) were obtained using an analysis of covariance (ANCOVA) model on data obtained from the multiple imputations (results were combined using Rubin's formulae).


Secondary Outcome Measures :
  1. Percentage of Participants With HbA1c <7 % at Week 26 [ Time Frame: Week 26 ]
    Participants who had no available assessment at Week 26 were considered as non-responders.

  2. Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 [ Time Frame: Baseline to Week 26 ]
    All values up to Week 26 were taken into account in the analysis, regardless of adherence to treatment. Change in FPG was calculated by subtracting baseline value from Week 26 value. Missing changes at Week 26 were imputed using a retrieved dropout multiple imputation method (separately for participants who prematurely discontinued or completed treatment). Adjusted LS means and SE were obtained using ANCOVA analysis on data obtained from the multiple imputations (results were combined using Rubin's formulae).

  3. Change in the Mean 24-hour Plasma Glucose Concentration From Baseline to Week 26 [ Time Frame: Baseline to 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 the week before a visit. All calculated values up to Week 26 were taken into account in the analysis, regardless of adherence to treatment. Change in mean 24-hour plasma glucose concentration was calculated by subtracting baseline value from Week 26 value. Missing changes at Week 26 were imputed using a return-to-baseline multiple imputation method (values imputed as participant baseline plus an error). Adjusted LS means and SE were obtained using ANCOVA analysis on data obtained from the multiple imputations (results were combined using Rubin's formulae).

  4. Change in Postprandial Plasma Glucose (PPG) Excursion From Baseline to Week 26 [ Time Frame: Baseline to 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 the average across profiles performed in the week before the visit. All calculated values up to Week 26 were taken into account in the analysis, regardless of adherence to treatment. Change in PPG excursions was calculated by subtracting baseline value from Week 26 value. Missing changes at Week 26 were imputed using a return-to-baseline multiple imputation method (values imputed as participant baseline plus an error). Adjusted LS means and SE were obtained using ANCOVA analysis on data obtained from the multiple imputations (results were combined using Rubin's formulae).

  5. Change in 7-Point SMPG Profiles From Baseline to Week 26 Per Time Point [ Time Frame: Baseline, Week 26 ]
    7-point SMPG profiles were measured at the following 7 points at each visit (Baseline, Week 26): before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, and bedtime. For each time point, the value at each visit was calculated as the average of values obtained for the same time point across profiles performed in the week before the visit.

  6. Number of Participants With at Least One Hypoglycemic Event [ Time Frame: From first injection of investigational medicinal product (IMP) up to Week 26 or up to 1 day after the last injection of IMP, whichever comes earlier ]
    Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because the participant was not capable of helping self. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=3.9 mmol/L (<=70 mg/dL) or plasma glucose level of <3.0 mmol/L (54 mg/dL). Percentage of participants with at least one hypoglycemia event (any, severe and documented [both thresholds]) were reported.

  7. Number of Hypoglycemia Events Per Participant-Year [ Time Frame: From first injection of IMP up to Week 26 or up to 1 day after the last injection of IMP, whichever come earlier ]
    Number of hypoglycemia events (any, severe and documented [both thresholds]) 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, because the participant was not capable of helping self. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=3.9 mmol/L (<=70 mg/dL) or plasma glucose level of <3.0 mmol/L (54 mg/dL).

  8. Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions [ Time Frame: From first injection of IMP up to Week 26 or up to 1 day after the last injection of IMP, whichever come earlier ]
    Participants with at least one treatment-emergent adverse event linked to hypersensitivity reaction and injection site reaction regardless of relationship to IMP during the main 6-month on-treatment period was assessed and reported.

  9. Percentage of Participants With at Least One Positive Anti-Insulin Aspart Antibodies (AIA) Sample [ Time Frame: From baseline up to Week 26 or up to 1 day after the last injection of IMP, whichever come earlier ]
    Participants with at least one positive AIA sample at baseline or at any time during the on-treatment period (Prevalence).

  10. Percentage of Participants With Treatment Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs) [ Time Frame: From first injection of IMP up to Week 26 or up to 1 day after the last injection of IMP, whichever come earlier ]
    AIA incidence were categorized as: treatment-induced, treatment-boosted AIAs, and treatment-emergent AIA. 1) 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. 2) 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). 3) Participants with treatment-emergent AIA were defined as participants with treatment-induced, or treatment-boosted AIAs.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Participants with T1DM or T2DM (T2DM US only) diagnosed for at least 12 months, who have been treated with a multiple daily injection regimen with
  • NovoLog/NovoRapid OR insulin lispro (100 U/mL) in the last 6 months prior to screening visit AND
  • insulin glargine (100 U/mL) in the last 6 months prior to screening visit OR insulin detemir (Levemir®) in the last 12 months prior to screening visit.

Exclusion criteria:

  • At screening visit, age under legal age of adulthood.
  • HbA1c <7.0% or >10% at screening.
  • Less than 1 year on continuous insulin treatment.
  • Use of insulin pump in the last 3 months before screening visit.
  • Participants with incomplete baseline 7-point SMPG profile, defined as participants who do not have 7-point profiles with at least 5 points on at least 2 days in the week before randomization Visit 3.
  • Participants with T1DM: Use of glucose lowering agents other than insulin including use of non-insulin injectable peptides in the last 3 months prior to screening.
  • Participants with T2DM:

    • Use of glucagon-like peptide-1 (GLP-1) receptor agonists in the last 3 months before screening visit.
    • Use of oral antidiabetic drugs (OADs) not on stable dose in the last 3 months before screening visit (sulfonylureas will be discontinued at baseline).
  • At screening visit, body mass index (BMI) >=35 kilogram per meter square (kg/m^2) in participants with T1DM and >=40 kg/m^2 in participants with T2DM.
  • Use of insulin other than:

    • insulin glargine 100 U/mL and NovoLog/NovoRapid or insulin lispro 100 U/mL as part of a multiple injection regimen in the last 6 months before screening visit, OR
    • insulin detemir 100 U/mL in the 12 months before screening visit and NovoLog/NovoRapid or insulin lispro 100 U/mL in the last 6 months before screening visit as part of a multiple injection regimen.
  • Status post pancreatectomy.
  • Status post pancreas and/or islet cell transplantation.
  • Hospitalization for recurrent diabetic ketoacidosis in the last 3 months before screening visit.
  • History of severe hypoglycemia requiring Emergency Room admission or hospitalization in the last 3 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.
  • Pregnant or breastfeeding women.
  • Women of childbearing potential not protected by highly effective method(s) of birth control.

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03211858


  Show 82 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] December 13, 2017
Statistical Analysis Plan  [PDF] February 28, 2018


Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03211858     History of Changes
Other Study ID Numbers: EFC15081
2017-000091-28 ( EudraCT Number )
U1111-1191-5775 ( Other Identifier: UTN )
First Posted: July 7, 2017    Key Record Dates
Results First Posted: August 8, 2019
Last Update Posted: August 8, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Insulin
Insulin, Globin Zinc
Insulin Glargine
Insulin Aspart
Insulin Lispro
Insulin, Long-Acting
Insulin degludec, insulin aspart drug combination
Diabetes Mellitus
Diabetes Mellitus, Type 2
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs