Primary Objective: To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (FRC) to insulin glargine in glycated hemoglobin (HbA1c) change from baseline to Week 30. Secondary Objective: To compare the overall efficacy and safety of insulin glargine/lixisenatide FRC to insulin glargine (with or without metformin) over a 30 week treatment period in participants with type 2 diabetes.
Maximum duration of approximately 39 weeks: an up to 8-week screening period, a 30-week randomized treatment period and 3 days post-treatment safety follow up period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
736
Insulin glargine/lixisenatide FRC was self-administered by subcutaneous (SC) injection within 1 hour before breakfast using one of 2 SoloStar® pen-injectors: Pen A (ratio of 2 Units (U) of insulin glargine U 100:1 mcg of lixisenatide) or Pen B (ratio of 3 U of insulin glargine U 100:1 mcg of lixisenatide). After run-in, the FRC was initiated at a dose of either 20 U/10 mcg with Pen A or 30 U/10 mcg with Pen B, depending on participant's dose of Insulin glargine on the day prior to randomization. Dose was adjusted weekly to reach and maintain fasting self-monitored plasma glucose (SMPG) of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L). Pen A was used for administration of doses up to 40 U/20 mcg and Pen B for administration of doses from 30 U/10 mcg up to 60 U/20 mcg.
Insulin glargine was self-administered QD by SC injection at approximately the same time every day. After screening, eligible participants entered 6 week run-in phase during which they were switched (if necessary) to insulin glargine and dose was stabilized. The first dose after randomization was same as the one administered on the day prior to randomization and then dose was adjusted weekly to reach and maintain fasting SMPG of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L).
Change in Glycated Hemoglobin (HbA1c) From Baseline to Week 30
Change in HbA1c was calculated by subtracting baseline value from Week 30 value.
Time frame: Baseline, Week 30
Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30
Time frame: Week 30
Change in 2-hour Plasma Blood Glucose Excursion From Baseline to Week 30
Plasma glucose excursion = 2-hour postprandial glucose (PPG) minus plasma glucose value obtained 30 minutes prior to the start of the meal and before investigational medicinal product (IMP) administration, if IMP was injected before breakfast. Change in plasma glucose excursions was calculated by subtracting baseline value from Week 30 value.
Time frame: Baseline, Week 30
Change in Body Weight From Baseline to Week 30
Change in body weight was calculated by subtracting baseline value from Week 30 value.
Time frame: Baseline, Week 30
Mean Change in 7-point Self-monitored Plasma Glucose (SMPG) Profile From Baseline to Week 30
Participants recorded a 7-point plasma glucose profile measured before and 2-hours after each meal and at bedtime, two times in a week before baseline, before visit Week 12 and before visit Week 30 and the average value across the profiles performed in the week before a visit for the 7 time points was calculated. Change in average 7 point SMPG was calculated by subtracting baseline value from Week 30 value. The analysis included all scheduled measurements obtained during the study. The missing data was handled by mixed effect model with repeated measures (MMRM) approach.
Time frame: Baseline, Week 30
Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30
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Pharmaceutical form: Tablet; Route of administration: Oral administration
Investigational Site Number 840607
Birmingham, Alabama, United States
Investigational Site Number 840570
Sun City, Arizona, United States
Investigational Site Number 840562
Tempe, Arizona, United States
Investigational Site Number 840577
Tucson, Arizona, United States
Investigational Site Number 840517
Little Rock, Arkansas, United States
Investigational Site Number 840537
Little Rock, Arkansas, United States
Investigational Site Number 840568
Bell Gardens, California, United States
Investigational Site Number 840550
Chino, California, United States
Investigational Site Number 840529
Chula Vista, California, United States
Investigational Site Number 840623
Corona, California, United States
...and 226 more locations
Time frame: Week 30
Change in Daily Insulin Glargine Dose From Baseline to Week 30
Time frame: Baseline, Week 30
Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 and No Documented Symptomatic Hypoglycemia (Plasma Glucose [PG] ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period
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).
Time frame: Baseline up to Week 30
Change in FPG From Baseline to Week 30
Change in FPG was calculated by subtracting baseline value from Week 30 value.
Time frame: Baseline, Week 30
Change in 2-hour PPG From Baseline to Week 30
Change in PPG was calculated by subtracting baseline value from Week 30 value.
Time frame: Baseline, Week 30
Percentage of Participants Reaching HbA1c <7.0% With No Documented Symptomatic Hypoglycemia (PG ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period
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).
Time frame: Baseline up to Week 30
Percentage of Participants Requiring Rescue Therapy During 30-Week Treatment Period
Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after Week 12) were performed. Threshold values - from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 30: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8%.
Time frame: Baseline up to Week 30
Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year
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).
Time frame: First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])
Percentage of Participants With Documented Symptomatic Hypoglycemia
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).
Time frame: First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])
Percentage of Participants With Severe Symptomatic Hypoglycemia
Severe symptomatic hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Plasma glucose measurements might not had been available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal was considered sufficient evidence that the event had been induced by a low plasma glucose concentration. Severe symptomatic hypoglycemia included all episodes in which neurological impairment was severe enough to prevent self-treatment, and which were thus thought to place participants at risk for injury to themselves or others.
Time frame: First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])