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Efficacy and Safety of Toujeo® Versus Tresiba® in Insulin-Naive Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Oral Antihyperglycemic Drug(s) ± GLP-1 Receptor Agonist (BRIGHT)

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ClinicalTrials.gov Identifier: NCT02738151
Recruitment Status : Completed
First Posted : April 14, 2016
Results First Posted : September 14, 2018
Last Update Posted : September 14, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To demonstrate the noninferiority in the efficacy of Toujeo® to Tresiba® in glycated hemoglobin (HbA1c) change from Baseline to Week 24.

Secondary Objectives:

Change From Baseline in HbA1c to Week 12

To assess the effects of the insulin Toujeo® in comparison with insulin Tresiba® at week 12 and week 24 on:

  • Change in Fasting plasma glucose (FPG);
  • Change in Fasting self-monitored plasma glucose (SMPG) and 4-point SMPG and 8-point SMPG profile;
  • Percentage of participants reaching HbA1c targets <7% or ≤6.5%;
  • Percentage of participants reaching HbA1c targets <7% or ≤6.5% without severe and/or confirmed hypoglycemia
  • Frequency of occurrence and diurnal distribution of hypoglycemia by American Diabetes Association (ADA) category of hypoglycemia.

To assess the safety in each treatment group.

To assess the treatment effects in each treatment group on Patient Reported Outcomes (PRO).

Percentage of participants requiring rescue therapy.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Insulin glargine, 300U/mL Drug: Insulin degludec, 100 U/mL Drug: Non-insulin anti-diabetic treatment Phase 4

Detailed Description:
The maximum study duration per participant was approximately 27 weeks: an up to 2-week screening period, a 24-week randomized treatment period (including 12 weeks active titration), and a 7-day posttreatment safety follow-up period.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 929 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 24-week, Multicenter, Randomized, Open-Label, Parallel-group StudyComparing the Efficacy and Safety of Toujeo® and Tresiba® in Insulin-NaivePatients With Type 2 Diabetes Mellitus Not Adequately Controlled With OralAntihyperglycemic Drug(s) ± GLP-1 Receptor Agonist
Study Start Date : May 19, 2016
Actual Primary Completion Date : August 15, 2017
Actual Study Completion Date : August 15, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Toujeo
Toujeo® (Insulin glargine, 300 U/mL) subcutaneous (SC) injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Drug: Insulin glargine, 300U/mL
Self-administered by subcutaneous (SC) injection in the evening using a pre-filled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 80 to 100 mg/dL (4.4 to 5.6 mmol/L).
Other Names:
  • HOE901-U300
  • Toujeo

Drug: Non-insulin anti-diabetic treatment
Background therapy: Oral Anti diabetics Drugs (OADs), Glucagon-like peptide-1 (GLP-1) receptor agonist.

Active Comparator: Tresiba
Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment .
Drug: Insulin degludec, 100 U/mL

Self-administered by subcutaneous (SC) injection in the evening using a pre-filled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 80 to 100 mg/dL (4.4 to 5.6 mmol/L).

Route of administration: subcutaneous

Other Name: Tresiba

Drug: Non-insulin anti-diabetic treatment
Background therapy: Oral Anti diabetics Drugs (OADs), Glucagon-like peptide-1 (GLP-1) receptor agonist.




Primary Outcome Measures :
  1. Change From Baseline in HbA1c to Week 24 [ Time Frame: Baseline, Week 24 ]
    Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Adjusted Least Square (LS) 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 24-week on-treatment period.


Secondary Outcome Measures :
  1. Change From Baseline in HbA1c to Week 12 [ Time Frame: Baseline, Week 12 ]
    Change in HbA1c was calculated by subtracting baseline value from Week 12 value. Adjusted least square means and standard errors were obtained from a mixed-effect model with MMRM.

  2. Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ]
    Change in FPG was calculated by subtracting baseline value from Week 12 and Week 24 value. Adjusted LS means were obtained from MMRM including post baseline values during the 24-week on-treatment period.

  3. Change From Baseline in Fasting Self-Monitoring Plasma Glucose (SMPG) to Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ]
    Fasting SMPG was measured by the participant before breakfast and before the administration of the glucose-lowering agents once a day during the study. Adjusted LS means were obtained from MMRM including post baseline values during the 24 week on treatment period.

  4. Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point [ Time Frame: Baseline, Week 12 and Week 24 ]
    8-point SMPG profiles were measured at the following 8 points: 03:00 at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime.

  5. Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point [ Time Frame: Baseline, Week 12 and Week 24 ]
    4-point SMPG profiles were measured at the following 4 points: prebreakfast, prelunch, predinner and bedtime.

  6. Change From Baseline in 24-hour Average 8-point SMPG Profile to Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ]
    The 8-point SMPG profile was measured at the following 8 points: 03:00 at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Adjusted LS means were obtained from MMRM.

  7. Change From Baseline in Variability of Fasting SMPG to Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ]
    Adjusted LS means were obtained from MMRM. Variability was assessed by the mean of coefficient of variation calculated over at least 3 SMPG measured during the 7 days preceding the given visit.

  8. Change From Baseline in Variability of 24-Hour 8-Point SMPG Profiles at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ]
    Adjusted LS means were obtained from MMRM.

  9. Percentage of Participants Reaching Target HbA1c of < 7% and =<6.5% at Week 12 and Week 24 [ Time Frame: Week 12, and Week 24 ]
    Only the post-baseline HbA1c measurements before rescue and during the 12 week and 24-week on-treatment period were considered in the analysis.

  10. Percentage of Participants Reaching Target HbA1c <7% and =<6.5% at Week 12 and Week 24 Without Severe and/or Confirmed Hypoglycemia (70 mg/dL) Event [ Time Frame: Week 12, and Week 24 ]
    Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed by plasma glucose =<3.9 mmol/L (=<70 mg/dL).

  11. Percentage of Participants With Sulphonylurea or Meglitinide Dose Reduction/ Discontinuation Due to Hypoglycemia During 24 Weeks Treatment Period [ Time Frame: Baseline to Week 24 ]
    Percentage of participants With Sulphonylurea or Meglitinide dose reduction/ discontinuation due to Hypoglycemia during 24 Week treatment period were reported. Only participants with Sulphonylurea or meglitinides at Screening as per actual strata were taken into account in this analysis.

  12. Percentage of Participants Requiring a Rescue Therapy During 24 Weeks Treatment Period [ Time Frame: Baseline to Week 24 ]
    Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. Threshold values at Week 12: FPG >200 mg/dL (11 mmol/L), or HbA1c >8.5%.

  13. Change From Baseline in Basal Insulin Dose (U/kg Body Weight) to Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ]
    Only the insulin dose measurements performed before initiation of rescue therapy and during the on-treatment period were considered in the analysis.

  14. Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period [ Time Frame: Day 1-Week 12, Week 13-Week 24, and 24 Week Period ]
    Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed with plasma glucose =<70 mg/dL (=<3.9 mmol/L), or < 54 mg/dL (<3.0 mmol/L). Assessment was done by treatment period (for =<12 weeks, for >12 weeks to =<24 weeks (24W)). Percentage of participants with at least one hypoglycemia (hypo) event at any time of the day were reported.

  15. Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period [ Time Frame: Day 1-Week 12, Week 13-Week 24, and 24 Week Period ]
    Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycaemia event was a severe event or an event confirmed with plasma glucose =<70 mg/dL (=<3.9 mmol/L), or < 54 mg/dL (<3.0 mmol/L). Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time). Assessment was done by treatment period (for =<12 weeks, for >12 weeks to =<24 weeks).

  16. Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period [ Time Frame: Day 1-Week 12, Week 13-Week 24, and 24 Week Period ]
    Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed with plasma glucose =<70 mg/dL (=<3.9 mmol/L), or < 54 mg/dL (<3.0 mmol/L).

  17. Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period [ Time Frame: Day 1-Week 12, Week 13-Week 24, and 24 Week Period ]
    Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed with plasma glucose =<70 mg/dL (=<3.9 mmol/L), or < 54 mg/dL (<3.0 mmol/L). Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time).


Other Outcome Measures:
  1. Change From Baseline in Total Diabetes Treatment Satisfaction Questionnaire (DTSQ) Status at Week 12 and Week 24 [ Time Frame: Baseline, Week 12 and Week 24 ]
    The DTSQs is a validated questionnaire to assess participant's satisfaction with their diabetes treatment. It consists of 8 items that are answered on a Likert scale from 0 to 6. Total treatment satisfaction score is the sum of items 1, 4-8 scores and ranged from 0 (no satisfaction) to 36 (high satisfaction with treatment). Adjusted least square means and standard errors were obtained from a mixed-effect model with MMRM.



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.


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

Inclusion criteria :

  • Adult participants with type 2 diabetes mellitus (T2DM) inadequately controlled with OADs therapy with/without GLP-1 receptor agonist at stable dose for at least 3 months.
  • Signed written informed consent.

Exclusion criteria:

  • Age <18 years.
  • HbA1c <7.5% or >10.5% (at screening visit). Body mass index (BMI) <25 kg/m^2 or >40 kg/m^2.
  • History of T2DM for less than 1 year before screening.
  • Less than 6 months before screening on OADs treatment and GLP-1 receptor agonist (if taken).
  • Current or previous insulin use except for a maximum of 8 consecutive days or totally 15 days (eg, acute illness, surgery) during the last year prior to screening.
  • Initiation of new glucose-lowering medications and/or weight loss drug in the last 3 months before screening visit.
  • Participant receiving only noninsulin antihyperglycemic drugs not approved for combination with insulin according to local labelling/local treatment guideline.
  • History of hypoglycemia unawareness or repeated episodes of severe hypoglycemia or metabolic acidosis, including hospitalization for diabetic ketoacidosis during the last 12 months prior to screening.
  • 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.
  • End stage renal disease.
  • Any acute or chronic condition that in the opinion of Investigator would affect the safety of participant, compliance, or study results.
  • Any contraindication to use of Toujeo® or Tresiba® as defined in the national product label, hypersensitivity to Toujeo® or Tresiba® active ingredients or one of the excipients.
  • Pregnant or breast-feeding women.

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): NCT02738151


  Show 158 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] December 18, 2015
Statistical Analysis Plan  [PDF] July 3, 2017


Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02738151     History of Changes
Other Study ID Numbers: LPS14584
2015-005101-36 ( EudraCT Number )
U1111-1177-6327 ( Other Identifier: UTN )
First Posted: April 14, 2016    Key Record Dates
Results First Posted: September 14, 2018
Last Update Posted: September 14, 2018
Last Verified: August 2018

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin
Insulin Glargine
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs