GetGoal-Duo-2: Efficacy and Safety of Lixisenatide Versus Insulin Glulisine on Top of Insulin Glargine With or Without Metformin in Type 2 Diabetic Patients
Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT01768559
Collaborator
(none)
894
199
3
23
4.5
0.2
Study Details
Study Description
Brief Summary
Primary Objective:
- To compare lixisenatide versus insulin glulisine in terms of glycosylated hemoglobin (HbA1c) reduction and body weight change at Week 26 in type 2 diabetic participants not adequately controlled on insulin glargine ± metformin.
Secondary Objectives:
-
To compare the treatments/regimens on:
-
The percentage of participants reaching the target of HbA1c <7% or ≤6.5%,
-
Body weight,
-
Self-Monitored Glucose profiles,
-
Fasting Plasma Glucose (FPG),
-
Post-prandial plasma glucose (PPG) /glucose excursions during a standardized meal test (subset of participants),
-
Daily doses of insulins,
-
Safety and tolerability.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Approximately 41 weeks including a 26 week treatment period.
Study Design
Study Type:
Interventional
Actual Enrollment
:
894 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open-label, Active-controlled, 3-arm Parallel-group, 26-week Study Comparing the Efficacy and Safety of Lixisenatide to That of Insulin Glulisine Once Daily and Insulin Glulisine Three Times Daily in Patients With Type 2 Diabetes Insufficiently Controlled With Insulin Glargine With or Without Metformin
Study Start Date
:
Jan 1, 2013
Actual Primary Completion Date
:
Dec 1, 2014
Actual Study Completion Date
:
Dec 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Lixisenatide Lixisenatide 10 mcg once daily (QD) for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. |
Drug: Lixisenatide (AVE0010)
Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection 30 to 60 minutes before breakfast or dinner.
Other Names:
Drug: Insulin Glargine (Mandatory background drug)
Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection at breakfast or dinner. Doses were adjusted to maintain a fasting self-monitored plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL).
Other Names:
Drug: Metformin (Background drug)
Pharmaceutical form: Tablet; Route of administration: Oral administration. If previously taken, Metformin to be continued at stable dose (≥1.5 g/day) throughout the study.
|
| Active Comparator: Insulin Glulisine QD Insulin glulisine QD from randomization up to Week 26 on top of Insulin glargine with or without metformin. |
Drug: Insulin glulisine QD
Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection within 15 minutes before breakfast or dinner. The initial dose was 3-5 units and then individually titrated to obtain the SMPG value >5.6 mmol/L (100 mg/dL) and ≤7.8 mmol/L (140 mg/dL) before lunch (if administered at breakfast) or at bedtime (if administered at dinner).
Other Names:
Drug: Insulin Glargine (Mandatory background drug)
Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection at breakfast or dinner. Doses were adjusted to maintain a fasting self-monitored plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL).
Other Names:
Drug: Metformin (Background drug)
Pharmaceutical form: Tablet; Route of administration: Oral administration. If previously taken, Metformin to be continued at stable dose (≥1.5 g/day) throughout the study.
|
| Active Comparator: Insulin Glulisine TID Insulin glulisine thrice daily (TID) from randomization up to Week 26 on top of Insulin glargine with or without metformin. |
Drug: Insulin glulisine TID
Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection within 15 minutes before each meal. The initial dose was 3-5 units for each meal and then individually titrated to obtain the SMPG value >5.6 mmol/L (100 mg/dL) and ≤7.8 mmol/L (140 mg/dL) before the next meal or at bedtime (for injection at dinner).
Other Names:
Drug: Insulin Glargine (Mandatory background drug)
Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection at breakfast or dinner. Doses were adjusted to maintain a fasting self-monitored plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL).
Other Names:
Drug: Metformin (Background drug)
Pharmaceutical form: Tablet; Route of administration: Oral administration. If previously taken, Metformin to be continued at stable dose (≥1.5 g/day) throughout the study.
|
Outcome Measures
Primary Outcome Measures
- Change in HbA1c From Baseline to Week 26 [Baseline, Week 26]
Change in HbA1C was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using last on-treatment observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.
- Change in Body Weight From Baseline to Week 26 [Baseline, Week 26]
Primary outcome was the comparison between Lixisenatide versus Insulin Glulisine TID. Change in body weight was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug.
Secondary Outcome Measures
- Percentage of Participants With HbA1c Level <7% and ≤6.5% at Week 26 [Week 26]
The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Missing data was imputed using LOCF.
- Percentage of Participants With no Weight Gain at Week 26 [Week 26]
The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 3 days after the last dose of study drug.
- Change in Average 7-point SMPG Profiles From Baseline to Week 26 [Baseline, Week 26]
Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime three times in a week before baseline, before visit Week 12 and before visit week 26 and the average value across the profiles performed in the week a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to the day of last dose of study drug.
- Change in FPG From Baseline to Week 26 [Baseline, Week 26]
Change in FPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 1 day after the last dose of study drug.
- Change in PPG From Baseline to Week 26 (in Participants Who Had an Injection of Investigational Medicinal Product [IMP] Before Breakfast) [Baseline, Week 26]
The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.
- Change in Glucose Excursions From Baseline to Week 26 (in Participants Who Had an Injection of IMP Before Breakfast) [Baseline, Week 26]
Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change in glucose excursions was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.
- Change in Insulin Glargine Dose From Baseline to Week 26 [Baseline, Week 26]
Change in Insulin glargine dose was calculated by subtracting the baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.
- Insulin Glulisine Dose at Week 26 [Week 26]
The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF.
- Total Insulin Dose at Week 26 [Week 26]
The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF. The outcome is reporting results of total insulin (amounts of Insulin Glargine plus Insulin Glulisine ) only for the arms in which Insulin Glulisine was administered and is not applicable for the lixisenatide arm in which only Insulin Glargine is administered. Change in dose of the insulin used by patients in the Lixisenatide arm (i.e. Insulin Glargine) is reported in the secondary Outcome Measure 9.
- Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia [First dose of study drug up to 3 days after the last dose administration (maximum of 185 days)]
Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <60 mg/dL (3.3 mmol/L). Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the participant required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.
- Percentage of Participants Who Reached the Target of HbA1c <7% at Week 26 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26 Week Treatment Period [Week 26]
The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug.
- Percentage of Participants Who Reached the Target of HbA1c <7% and Had no Weight Gain at Week 26 [Week 26]
The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug.
- Percentage of Participants Who Reached the Target of HbA1c <7%, Had no Weight Gain at Week 26, and Did Not Experience Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26-Week Treatment Period [Week 26]
The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug. Participants without post-baseline on-treatment values (HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (HbA1c and/or body weight) was available and showed non-response, or if they experienced at least one documented symptomatic hypoglycemia during the on-treatment period. Otherwise, they were counted as missing data.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria :
-
Participants with type 2 diabetes mellitus diagnosed at least 1 year before screening visit (V1).
-
Participants treated with basal insulin for at least 6 months.
-
Participants treated for at least 3 months prior to visit 1 with a stable basal insulin regimen (i.e. type of insulin and time/frequency of the injection). The insulin dose should be stable (± 20%) and ≥20 U/day for at least 2 months prior to visit 1.
-
Participants treated with basal insulin alone or in combination with 1 to 3 oral anti-diabetic drugs (OADs) that could be: metformin (≥1.5 g/day or maximal tolerated dose), a sulfonylurea (SU), a dipeptidyl-peptidase-4 (DPP-4) inhibitor, a glinide. The dose of OADs should be stable for at least 3 months prior to visit 1.
Exclusion criteria:
-
At screening: age < legal age of majority.
-
At screening, HbA1c: <7.5% and >10.0% for participants treated with basal insulin alone or in combination with metformin only; < 7.0% and > 10.0% for participants treated with basal insulin and a combination of oral anti-diabetic drugs which included a SU and/or a DPP-4 inhibitor and/or a glinide.
-
Women of childbearing potential with no effective contraceptive method, pregnancy or lactation.
-
Type 1 diabetes mellitus.
-
Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria within 3 months prior to screening.
-
Previous treatment with short or rapid acting insulin other than in relation to hospitalization or an acute illness.
-
Any previous treatment with lixisenatide, or any discontinuation from another glucagon-like peptide 1 (GLP-1) receptor agonist due to safety/tolerability issue or lack of efficacy.
-
At screening, Body Mass Index (BMI) ≤20 or >40 kg/m^2.
-
Weight change of more than 5 kg during the 3 months prior to the screening visit; use of weight loss drugs within 3 months prior to screening.
-
Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures.
-
History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery.
-
At screening resting systolic blood pressure >180 mmHg or diastolic blood pressure >95 mmHg.
-
Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposed to MTC (e.g. multiple endocrine neoplasia syndromes).
-
Contraindication related to metformin (for participant receiving this treatment), insulin glargine, insulin glulisine or lixisenatide.
-
Participants with severe renal impairment (creatinine clearance less than 30 ml/min) or end-stage renal disease.
-
At screening, amylase and/or lipase >3 times the upper limit of the normal laboratory range (ULN).
-
At screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 ULN.
-
At screening calcitonin ≥20 pg/ml (5.9 pmol/L).
Exclusion Criteria for randomization at the end of the screening period before randomization:
-
HbA1c <7.0% or >9.0%.
-
7-day mean fasting SMPG >140 mg/dl (7.8 mmol/L).
-
Amylase and/or lipase >3 times ULN.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site Number 840043 | Sun City | Arizona | United States | 85351 |
| 2 | Investigational Site Number 840042 | Tempe | Arizona | United States | 85282 |
| 3 | Investigational Site Number 840003 | Little Rock | Arkansas | United States | 72205 |
| 4 | Investigational Site Number 840031 | La Mesa | California | United States | 91942 |
| 5 | Investigational Site Number 840005 | Mission Viejo | California | United States | 92691 |
| 6 | Investigational Site Number 840057 | Northridge | California | United States | 91325 |
| 7 | Investigational Site Number 840035 | Santa Ana | California | United States | 92704 |
| 8 | Investigational Site Number 840002 | Temecula | California | United States | 92591 |
| 9 | Investigational Site Number 840037 | Walnut Creek | California | United States | 94598 |
| 10 | Investigational Site Number 840023 | West Hills | California | United States | 91345 |
| 11 | Investigational Site Number 840041 | Denver | Colorado | United States | 80246 |
| 12 | Investigational Site Number 840012 | Miami | Florida | United States | 33136 |
| 13 | Investigational Site Number 840061 | Miami | Florida | United States | 33142 |
| 14 | Investigational Site Number 840045 | Lawrenceville | Georgia | United States | 30045 |
| 15 | Investigational Site Number 840036 | Nampa | Idaho | United States | 83686 |
| 16 | Investigational Site Number 840024 | Chicago | Illinois | United States | 60611 |
| 17 | Investigational Site Number 840009 | Evanston | Illinois | United States | 60201 |
| 18 | Investigational Site Number 840004 | Avon | Indiana | United States | 46123 |
| 19 | Investigational Site Number 840055 | Avon | Indiana | United States | 46123 |
| 20 | Investigational Site Number 840027 | Des Moines | Iowa | United States | 50314 |
| 21 | Investigational Site Number 840006 | Wichita | Kansas | United States | 67203 |
| 22 | Investigational Site Number 840047 | Lexington | Kentucky | United States | 40504 |
| 23 | Investigational Site Number 840056 | Paducah | Kentucky | United States | 42003 |
| 24 | Investigational Site Number 840022 | Marrero | Louisiana | United States | 70072 |
| 25 | Investigational Site Number 840016 | Baltimore | Maryland | United States | 21237 |
| 26 | Investigational Site Number 840017 | Rockville | Maryland | United States | 20852 |
| 27 | Investigational Site Number 840025 | Buckley | Michigan | United States | 49620 |
| 28 | Investigational Site Number 840048 | Dearborn | Michigan | United States | 48124 |
| 29 | Investigational Site Number 840026 | Kalamazoo | Michigan | United States | 49048 |
| 30 | Investigational Site Number 840049 | Las Vegas | Nevada | United States | 89148 |
| 31 | Investigational Site Number 840029 | New Hyde Park | New York | United States | 11042 |
| 32 | Investigational Site Number 840060 | Smithtown | New York | United States | 11787 |
| 33 | Investigational Site Number 840030 | Staten Island | New York | United States | 10301-3914 |
| 34 | Investigational Site Number 840011 | Salisbury | North Carolina | United States | 28144 |
| 35 | Investigational Site Number 840028 | Fargo | North Dakota | United States | 58103 |
| 36 | Investigational Site Number 840007 | Oklahoma City | Oklahoma | United States | 73104 |
| 37 | Investigational Site Number 840021 | Pittsburgh | Pennsylvania | United States | 15212 |
| 38 | Investigational Site Number 840052 | Myrtle Beach | South Carolina | United States | 29572 |
| 39 | Investigational Site Number 840032 | Chattanooga | Tennessee | United States | 37404 |
| 40 | Investigational Site Number 840033 | Nashville | Tennessee | United States | 37232 |
| 41 | Investigational Site Number 840034 | Corpus Christi | Texas | United States | 78404 |
| 42 | Investigational Site Number 840001 | Dallas | Texas | United States | 75230 |
| 43 | Investigational Site Number 840020 | Houston | Texas | United States | 77081 |
| 44 | Investigational Site Number 840018 | Norfolk | Virginia | United States | 23502 |
| 45 | Investigational Site Number 840015 | Salem | Virginia | United States | 24153 |
| 46 | Investigational Site Number 840010 | Milwaukee | Wisconsin | United States | 53217 |
| 47 | Investigational Site Number 124008 | Brampton | Canada | L6R 3J5 | |
| 48 | Investigational Site Number 124015 | Burlington | Canada | L7M 4Y1 | |
| 49 | Investigational Site Number 124018 | Chatham | Canada | N7L 1C1 | |
| 50 | Investigational Site Number 124004 | Coquitlam | Canada | V3K 3P4 | |
| 51 | Investigational Site Number 124016 | Etobicoke | Canada | M9R 4E1 | |
| 52 | Investigational Site Number 124014 | Hamilton | Canada | L8L 5G8 | |
| 53 | Investigational Site Number 124020 | Montreal | Canada | H1Y 3L1 | |
| 54 | Investigational Site Number 124011 | Montreal | Canada | H3A 1A1 | |
| 55 | Investigational Site Number 124017 | Newmarket | Canada | L3Y 5G8 | |
| 56 | Investigational Site Number 124021 | Quebec | Canada | G1N 4V3 | |
| 57 | Investigational Site Number 124003 | Red Deer | Canada | T4N 6V7 | |
| 58 | Investigational Site Number 124002 | Sherbrooke | Canada | J1H 5N4 | |
| 59 | Investigational Site Number 124012 | St-Romuald | Canada | G6W 5M6 | |
| 60 | Investigational Site Number 124001 | Toronto | Canada | M4G 3E8 | |
| 61 | Investigational Site Number 124010 | Toronto | Canada | M5C 2T2 | |
| 62 | Investigational Site Number 124005 | Vancouver | Canada | V5Z 1M9 | |
| 63 | Investigational Site Number 124006 | Victoria | Canada | V8V 4A1 | |
| 64 | Investigational Site Number 124007 | Winnipeg | Canada | R3E 3P4 | |
| 65 | Investigational Site Number 152103 | Santiago | Chile | 7500010 | |
| 66 | Investigational Site Number 152107 | Santiago | Chile | 7500347 | |
| 67 | Investigational Site Number 152101 | Santiago | Chile | 7500710 | |
| 68 | Investigational Site Number 152105 | Santiago | Chile | 7591047 | |
| 69 | Investigational Site Number 152102 | Santiago | Chile | 7980378 | |
| 70 | Investigational Site Number 152106 | Santiago | Chile | 8053095 | |
| 71 | Investigational Site Number 152108 | Santiago | Chile | 8053095 | |
| 72 | Investigational Site Number 152109 | Santiago | Chile | ||
| 73 | Investigational Site Number 203107 | Beroun | Czech Republic | 26601 | |
| 74 | Investigational Site Number 203103 | Jilove U Prahy | Czech Republic | 254 01 | |
| 75 | Investigational Site Number 203101 | Ostrava 2 | Czech Republic | 702 00 | |
| 76 | Investigational Site Number 203110 | Police Nad Metuji | Czech Republic | 549 54 | |
| 77 | Investigational Site Number 203105 | Praha 4 | Czech Republic | 14021 | |
| 78 | Investigational Site Number 203102 | Praha 4 | Czech Republic | 148 00 | |
| 79 | Investigational Site Number 203108 | Praha 4 | Czech Republic | 14900 | |
| 80 | Investigational Site Number 203104 | Trutnov | Czech Republic | 54101 | |
| 81 | Investigational Site Number 233102 | Pärnu | Estonia | 80018 | |
| 82 | Investigational Site Number 233103 | Tallinn | Estonia | 13415 | |
| 83 | Investigational Site Number 233104 | Tallinn | Estonia | 13419 | |
| 84 | Investigational Site Number 233101 | Viljandimaa | Estonia | 71024 | |
| 85 | Investigational Site Number 250108 | Bois Guillaume | France | 76230 | |
| 86 | Investigational Site Number 250105 | Corbeil Essonnes | France | 91100 | |
| 87 | Investigational Site Number 250104 | La Rochelle Cedex | France | 17019 | |
| 88 | Investigational Site Number 250106 | Lyon | France | 69495 | |
| 89 | Investigational Site Number 250107 | Lyon | France | 69495 | |
| 90 | Investigational Site Number 250109 | Mantes La Jolie | France | 78200 | |
| 91 | Investigational Site Number 250102 | Paris Cedex 15 | France | 75908 | |
| 92 | Investigational Site Number 250101 | Vandoeuvre Les Nancy | France | 54511 | |
| 93 | Investigational Site Number 250103 | Venissieux | France | 69200 | |
| 94 | Investigational Site Number 276112 | Bad Mergentheim | Germany | 97980 | |
| 95 | Investigational Site Number 276108 | Berlin | Germany | 13125 | |
| 96 | Investigational Site Number 276102 | Dortmund | Germany | 44137 | |
| 97 | Investigational Site Number 276120 | Dresden | Germany | 01067 | |
| 98 | Investigational Site Number 276106 | Dresden | Germany | 01307 | |
| 99 | Investigational Site Number 276117 | Frankfurt A.M. | Germany | 60596 | |
| 100 | Investigational Site Number 276116 | Görlitz | Germany | 02826 | |
| 101 | Investigational Site Number 276113 | Heidelberg | Germany | 69115 | |
| 102 | Investigational Site Number 276118 | Leipzig | Germany | 04103 | |
| 103 | Investigational Site Number 276119 | Magdeburg | Germany | 39104 | |
| 104 | Investigational Site Number 276103 | Neumünster | Germany | 24534 | |
| 105 | Investigational Site Number 276115 | Speyer | Germany | 67346 | |
| 106 | Investigational Site Number 276109 | St. Ingbert-Oberwürzbach | Germany | 66386 | |
| 107 | Investigational Site Number 348107 | Budapest | Hungary | 1134 | |
| 108 | Investigational Site Number 348108 | Budapest | Hungary | 1138 | |
| 109 | Investigational Site Number 348102 | Budapest | Hungary | 1139 | |
| 110 | Investigational Site Number 348101 | Eger | Hungary | 3300 | |
| 111 | Investigational Site Number 348103 | Pápa | Hungary | 8500 | |
| 112 | Investigational Site Number 348104 | Szeged | Hungary | 6720 | |
| 113 | Investigational Site Number 348106 | Sátoraljaújhely | Hungary | 3980 | |
| 114 | Investigational Site Number 348105 | Zalaegerszeg | Hungary | 8900 | |
| 115 | Investigational Site Number 380103 | Bologna | Italy | 40138 | |
| 116 | Investigational Site Number 380102 | Catania | Italy | 95122 | |
| 117 | Investigational Site Number 380101 | Milano | Italy | 20132 | |
| 118 | Investigational Site Number 380105 | Napoli | Italy | 80131 | |
| 119 | Investigational Site Number 380104 | Torino | Italy | 10126 | |
| 120 | Investigational Site Number 428103 | Jelgava | Latvia | LV-3001 | |
| 121 | Investigational Site Number 428104 | Ogre | Latvia | LV-5001 | |
| 122 | Investigational Site Number 428102 | Riga | Latvia | LV-1002 | |
| 123 | Investigational Site Number 428105 | Riga | Latvia | LV-1006 | |
| 124 | Investigational Site Number 428101 | Sigulda | Latvia | LV-2150 | |
| 125 | Investigational Site Number 440104 | Jonava | Lithuania | LT-55201 | |
| 126 | Investigational Site Number 440103 | Kaunas | Lithuania | LT-48259 | |
| 127 | Investigational Site Number 440102 | Kaunas | Lithuania | LT-49456 | |
| 128 | Investigational Site Number 440101 | Kaunas | Lithuania | LT-51270 | |
| 129 | Investigational Site Number 440105 | Klaipeda | Lithuania | LT-92288 | |
| 130 | Investigational Site Number 484108 | Chihuahua | Mexico | 31200 | |
| 131 | Investigational Site Number 484101 | Cuernavaca | Mexico | 62250 | |
| 132 | Investigational Site Number 484111 | Durango | Mexico | 34080 | |
| 133 | Investigational Site Number 484104 | Guadalajara | Mexico | 44150 | |
| 134 | Investigational Site Number 484109 | Guadalajara | Mexico | 44210 | |
| 135 | Investigational Site Number 484107 | Guadalajara | Mexico | 44600 | |
| 136 | Investigational Site Number 484105 | Guadalajara | Mexico | 44650 | |
| 137 | Investigational Site Number 484110 | Guadalajara | Mexico | 44656 | |
| 138 | Investigational Site Number 484103 | Mexico Df | Mexico | 11850 | |
| 139 | Investigational Site Number 484106 | Monterrey | Mexico | 64000 | |
| 140 | Investigational Site Number 484102 | México | Mexico | 06700 | |
| 141 | Investigational Site Number 616101 | Bialystok | Poland | 15-435 | |
| 142 | Investigational Site Number 616103 | Bydgoszcz | Poland | 85-822 | |
| 143 | Investigational Site Number 616102 | Bytom | Poland | 41-902 | |
| 144 | Investigational Site Number 616106 | Krakow | Poland | 31-455 | |
| 145 | Investigational Site Number 616104 | Krakow | Poland | 31-548 | |
| 146 | Investigational Site Number 616105 | Pulawy | Poland | 24-100 | |
| 147 | Investigational Site Number 616107 | Warszawa | Poland | 02-507 | |
| 148 | Investigational Site Number 642105 | Bacau | Romania | 600114 | |
| 149 | Investigational Site Number 642108 | Cluj Napoca | Romania | 400006 | |
| 150 | Investigational Site Number 642106 | Deva | Romania | 330084 | |
| 151 | Investigational Site Number 642113 | Galati | Romania | 800098 | |
| 152 | Investigational Site Number 642107 | Hunedoara | Romania | 331057 | |
| 153 | Investigational Site Number 642117 | Iasi | Romania | 700547 | |
| 154 | Investigational Site Number 642103 | Oradea | Romania | 410169 | |
| 155 | Investigational Site Number 642104 | Oradea | Romania | 410169 | |
| 156 | Investigational Site Number 642112 | Pitesti | Romania | 110084 | |
| 157 | Investigational Site Number 642114 | Ploiesti | Romania | 100342 | |
| 158 | Investigational Site Number 642102 | Resita | Romania | 320076 | |
| 159 | Investigational Site Number 642111 | Sibiu | Romania | 550371 | |
| 160 | Investigational Site Number 642109 | Targu Mures | Romania | 540142 | |
| 161 | Investigational Site Number 642110 | Targu Mures | Romania | 540142 | |
| 162 | Investigational Site Number 642116 | Timisoara | Romania | 300133 | |
| 163 | Investigational Site Number 642101 | Timisoara | Romania | 300456 | |
| 164 | Investigational Site Number 642115 | Timisoara | Romania | 300723 | |
| 165 | Investigational Site Number 643111 | Moscow | Russian Federation | 117036 | |
| 166 | Investigational Site Number 643107 | Moscow | Russian Federation | 119991 | |
| 167 | Investigational Site Number 643105 | Moscow | Russian Federation | 129110 | |
| 168 | Investigational Site Number 643110 | Penza | Russian Federation | 440026 | |
| 169 | Investigational Site Number 643102 | Saratov | Russian Federation | 410030 | |
| 170 | Investigational Site Number 643101 | St-Petersburg | Russian Federation | 194044 | |
| 171 | Investigational Site Number 643104 | St-Petersburg | Russian Federation | 194354 | |
| 172 | Investigational Site Number 643109 | St-Petersburg | Russian Federation | 194354 | |
| 173 | Investigational Site Number 643108 | St-Petersburg | Russian Federation | 195112 | |
| 174 | Investigational Site Number 643103 | St-Petersburg | Russian Federation | 195257 | |
| 175 | Investigational Site Number 643106 | St. Petersburg | Russian Federation | 194358 | |
| 176 | Investigational Site Number 724102 | El Ferrol | Spain | 15403 | |
| 177 | Investigational Site Number 724105 | La Coruña | Spain | 15006 | |
| 178 | Investigational Site Number 724103 | Malaga | Spain | 29010 | |
| 179 | Investigational Site Number 724104 | Sevilla | Spain | 41010 | |
| 180 | Investigational Site Number 804104 | Chernivtsi | Ukraine | 58022 | |
| 181 | Investigational Site Number 804107 | Donetsk | Ukraine | 83003 | |
| 182 | Investigational Site Number 804103 | Donetsk | Ukraine | 83059 | |
| 183 | Investigational Site Number 804108 | Mykolaiv | Ukraine | 54003 | |
| 184 | Investigational Site Number 804110 | Odessa | Ukraine | 65059 | |
| 185 | Investigational Site Number 804105 | Vinnytsya | Ukraine | 21001 | |
| 186 | Investigational Site Number 804102 | Vinnytsya | Ukraine | 21010 | |
| 187 | Investigational Site Number 804111 | Zaporizhia | Ukraine | 69600 | |
| 188 | Investigational Site Number 826006 | Ashton-Under-Lyne | United Kingdom | OL6 9RW | |
| 189 | Investigational Site Number 826002 | Birmingham | United Kingdom | B9 5SS | |
| 190 | Investigational Site Number 826007 | Carmarthen | United Kingdom | SA31 2AF | |
| 191 | Investigational Site Number 826005 | Chester | United Kingdom | CH2 1UL | |
| 192 | Investigational Site Number 826008 | Coventry | United Kingdom | CV1 4FH | |
| 193 | Investigational Site Number 826009 | Dundee | United Kingdom | DD1 9SI | |
| 194 | Investigational Site Number 826001 | Durham | United Kingdom | DH1 5TW | |
| 195 | Investigational Site Number 826011 | Haddington | United Kingdom | EH41 3PF | |
| 196 | Investigational Site Number 826012 | Leicester | United Kingdom | LE5 4PW | |
| 197 | Investigational Site Number 826010 | Plymouth | United Kingdom | PL6 8BX | |
| 198 | Investigational Site Number 826004 | Sheffield | United Kingdom | S5 7AU | |
| 199 | Investigational Site Number 826003 | St Helens | United Kingdom | WA93DA |
Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT01768559
Other Study ID Numbers:
- EFC12626
- 2012-004096-38
- U1111-1131-4936
First Posted:
Jan 15, 2013
Last Update Posted:
Jan 4, 2017
Last Verified:
Nov 1, 2016
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 199 centers in 18 countries. A total of 2159 participants were screened between January 08, 2013 and April 10, 2014. |
|---|---|
| Pre-assignment Detail | Participants underwent a 12-week run-in period with switch from other basal insulins to insulin glargine. A total of 1265 participants were screen failures/run-in failures; the most frequent reason for run-in failure was that glycosylated hemoglobin (HbA1c) criteria were not met at the end of run-in phase. 894 participants were randomized. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg once daily (QD) subcutaneously (SC) for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine thrice daily (TID) SC up to Week 26 on top of insulin glargine with or without metformin. |
| Period Title: Overall Study | |||
| STARTED | 298 | 298 | 298 |
| Treated | 298 | 298 | 297 |
| COMPLETED | 268 | 281 | 285 |
| NOT COMPLETED | 30 | 17 | 13 |
Baseline Characteristics
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID | Total |
|---|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of insulin glargine with or without metformin. | Total of all reporting groups |
| Overall Participants | 298 | 298 | 298 | 894 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
59.8
(8.6)
|
60.2
(8.6)
|
59.4
(9.5)
|
59.8
(8.9)
|
| Gender (Count of Participants) | ||||
| Female |
160
53.7%
|
163
54.7%
|
166
55.7%
|
489
54.7%
|
| Male |
138
46.3%
|
135
45.3%
|
132
44.3%
|
405
45.3%
|
| Race (participants) [Number] | ||||
| Caucasian/White |
276
92.6%
|
280
94%
|
272
91.3%
|
828
92.6%
|
| Black |
13
4.4%
|
11
3.7%
|
12
4%
|
36
4%
|
| Asian/Oriental |
9
3%
|
7
2.3%
|
13
4.4%
|
29
3.2%
|
| Other |
0
0%
|
0
0%
|
1
0.3%
|
1
0.1%
|
| Ethnicity (participants) [Number] | ||||
| Hispanic |
63
21.1%
|
58
19.5%
|
68
22.8%
|
189
21.1%
|
| Non-Hispanic |
235
78.9%
|
240
80.5%
|
230
77.2%
|
705
78.9%
|
| Metformin Use at Screening (participants) [Number] | ||||
| Yes |
262
87.9%
|
260
87.2%
|
259
86.9%
|
781
87.4%
|
| No |
36
12.1%
|
38
12.8%
|
39
13.1%
|
113
12.6%
|
| Number of Participants with Categorical Body Mass Index (BMI) (participants) [Number] | ||||
| <30 kg/m^2 |
97
32.6%
|
118
39.6%
|
97
32.6%
|
312
34.9%
|
| ≥30 kg/m^2 |
201
67.4%
|
180
60.4%
|
200
67.1%
|
581
65%
|
| Participants not analyzed for BMI |
0
0%
|
0
0%
|
1
0.3%
|
1
0.1%
|
| BMI (kg/m^2) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg/m^2] |
32.27
(4.57)
|
31.86
(4.39)
|
32.50
(4.60)
|
32.21
(4.52)
|
| Weight (kg) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg] |
90.06
(17.31)
|
88.45
(15.84)
|
90.08
(17.18)
|
89.53
(16.79)
|
| HbA1c (percentage of hemoglobin) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [percentage of hemoglobin] |
7.77
(0.55)
|
7.73
(0.59)
|
7.79
(0.60)
|
7.76
(0.58)
|
| Fasting Plasma Glucose (FPG) (mmol/L) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mmol/L] |
6.58
(1.82)
|
6.84
(1.98)
|
6.65
(1.89)
|
6.69
(1.90)
|
| 2-Hour Postprandial Plasma Glucose (PPG) (mmol/L) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mmol/L] |
14.26
(3.55)
|
14.02
(3.59)
|
14.25
(3.35)
|
14.18
(3.47)
|
| 2-Hour Glucose Excursion (mmol/L) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mmol/L] |
7.31
(3.19)
|
7.31
(3.63)
|
7.35
(3.34)
|
7.33
(3.37)
|
| Average 7-Point Self-monitored Plasma Glucose (SMPG) (mmol/L) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mmol/L] |
9.02
(1.75)
|
9.07
(1.74)
|
8.99
(1.57)
|
9.02
(1.68)
|
| Insulin Glargine Dose (Units (U)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Units (U)] |
67.25
(31.95)
|
64.72
(32.07)
|
64.97
(26.90)
|
65.65
(30.39)
|
| Duration of Diabetes (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
11.89
(6.43)
|
12.33
(6.75)
|
12.41
(6.80)
|
12.21
(6.66)
|
Outcome Measures
| Title | Change in HbA1c From Baseline to Week 26 |
|---|---|
| Description | Change in HbA1C was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using last on-treatment observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period. |
| Time Frame | Baseline, Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| modified intent-to-treat (mITT) population: all randomized participants who received at least one dose of study drug; and had both baseline and at least one post-baseline efficacy assessment, irrespective of compliance with study protocol/procedures. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 292 | 292 | 295 |
| Least Squares Mean (Standard Error) [percentage of hemoglobin] |
-0.63
(0.054)
|
-0.58
(0.054)
|
-0.84
(0.053)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lixisenatide, Insulin Glulisine QD |
|---|---|---|
| Comments | Analysis was performed using analysis of covariance (ANCOVA) model with treatment groups, strata of Week -1 HbA1c (<8.0, ≥8.0%), randomization strata of metformin use, and country as fixed effects and baseline HbA1c value as a covariate. The non-inferiority was assessed using upper bound of 2-sided 95% Confidence Interval (CI). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Pre-specified non-inferiority margin of 0.4%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square (LS) Mean Difference |
| Estimated Value | -0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.17 to 0.064 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.059 |
|
| Estimation Comments | Lixisenatide vs Insulin Glulisine QD | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Lixisenatide, Insulin Glulisine TID |
|---|---|---|
| Comments | Analysis was performed using ANCOVA model as described above. Hochberg procedure was used to control type 1 error at significance level = 0.025 (1-sided) for comparison between Lixisenatide vs Insulin glulisine TID in HbA1c and body weight. If both comparisons were met, then both would be declared significant. Otherwise, if only one was met, then the one met should be tested at α=0.0125 (1-sided). | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Pre-specified non-inferiority margin of 0.4%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.21 | |
| Confidence Interval |
(2-Sided) 95% 0.095 to 0.328 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.059 |
|
| Estimation Comments | Lixisenatide vs Insulin Glulisine TID | |
| Title | Change in Body Weight From Baseline to Week 26 |
|---|---|
| Description | Primary outcome was the comparison between Lixisenatide versus Insulin Glulisine TID. Change in body weight was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. |
| Time Frame | Baseline, Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline body weight assessment during on-treatment period. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 295 | 295 | 295 |
| Least Squares Mean (Standard Error) [kg] |
-0.63
(0.276)
|
1.03
(0.276)
|
1.37
(0.271)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lixisenatide, Insulin Glulisine TID |
|---|---|---|
| Comments | Analysis was performed using ANCOVA model as described above. Hochberg procedure was used to control type 1 error at α = 0.025 (1-sided) for comparison between lixisenatide vs insulin glulisine TID in HbA1c and body weight. If both comparisons were met, then both would be declared significant. Otherwise, if only one was met, then the one met should be tested at α=0.0125 (1-sided). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | Threshold for significance at 0.025 level. | |
| Method | ANCOVA | |
| Comments | The superiority was assessed by comparing the P-value at significance level = 0.025 or 0.0125. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.99 | |
| Confidence Interval |
(2-Sided) 95% -2.593 to -1.396 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.305 |
|
| Estimation Comments | Lixisenatide vs Insulin Glulisine TID | |
| Title | Percentage of Participants With HbA1c Level <7% and ≤6.5% at Week 26 |
|---|---|
| Description | The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Missing data was imputed using LOCF. |
| Time Frame | Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 292 | 292 | 295 |
| HbA1c ≤6.5% |
20.5
6.9%
|
17.8
6%
|
30.8
10.3%
|
| HbA1c <7.0% |
42.1
14.1%
|
38.4
12.9%
|
49.2
16.5%
|
| Title | Percentage of Participants With no Weight Gain at Week 26 |
|---|---|
| Description | The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 3 days after the last dose of study drug. |
| Time Frame | Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline body weight assessment during on-treatment period. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 295 | 295 | 295 |
| Number [percentage of participants] |
64.7
21.7%
|
36.6
12.3%
|
30.5
10.2%
|
| Title | Change in Average 7-point SMPG Profiles From Baseline to Week 26 |
|---|---|
| Description | Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime three times in a week before baseline, before visit Week 12 and before visit week 26 and the average value across the profiles performed in the week a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to the day of last dose of study drug. |
| Time Frame | Baseline, Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline 7-point SMPG assessment during on-treatment period. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 270 | 268 | 278 |
| Least Squares Mean (Standard Error) [mmol/L] |
-0.784
(0.1141)
|
-0.782
(0.1133)
|
-1.053
(0.1105)
|
| Title | Change in FPG From Baseline to Week 26 |
|---|---|
| Description | Change in FPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 1 day after the last dose of study drug. |
| Time Frame | Baseline, Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline FPG assessment during on-treatment period. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 295 | 295 | 294 |
| Least Squares Mean (Standard Error) [mmol/L] |
-0.23
(0.143)
|
-0.21
(0.142)
|
-0.06
(0.14)
|
| Title | Change in PPG From Baseline to Week 26 (in Participants Who Had an Injection of Investigational Medicinal Product [IMP] Before Breakfast) |
|---|---|
| Description | The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. |
| Time Frame | Baseline, Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Here, number of participants analyzed = participants with IMP injection before breakfast and baseline and at least one post-baseline 2-hour PPG assessment during on-treatment period. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 69 | 55 | 68 |
| Mean (Standard Deviation) [mmol/L] |
-3.93
(4.29)
|
-1.62
(4.01)
|
-1.87
(3.18)
|
| Title | Change in Glucose Excursions From Baseline to Week 26 (in Participants Who Had an Injection of IMP Before Breakfast) |
|---|---|
| Description | Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change in glucose excursions was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. |
| Time Frame | Baseline, Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Here, number of participants analyzed = participants with IMP injection before breakfast and baseline and at least one post-baseline glucose excursion assessment during on-treatment period. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 64 | 53 | 66 |
| Mean (Standard Deviation) [mmol/L] |
-3.42
(4.13)
|
-1.59
(3.42)
|
-1.56
(2.52)
|
| Title | Change in Insulin Glargine Dose From Baseline to Week 26 |
|---|---|
| Description | Change in Insulin glargine dose was calculated by subtracting the baseline value from Week 26 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. |
| Time Frame | Baseline, Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline insulin glargine dose assessment during on-treatment period. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 292 | 294 | 294 |
| Least Squares Mean (Standard Error) [U] |
0.7
(1.002)
|
-0.06
(0.999)
|
-3.13
(0.982)
|
| Title | Insulin Glulisine Dose at Week 26 |
|---|---|
| Description | The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF. |
| Time Frame | Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline insulin glulisine dose assessment during on-treatment period. |
| Arm/Group Title | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|
| Arm/Group Description | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 295 | 293 |
| Mean (Standard Deviation) [U] |
9.97
(7.8)
|
20.24
(13.04)
|
| Title | Total Insulin Dose at Week 26 |
|---|---|
| Description | The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF. The outcome is reporting results of total insulin (amounts of Insulin Glargine plus Insulin Glulisine ) only for the arms in which Insulin Glulisine was administered and is not applicable for the lixisenatide arm in which only Insulin Glargine is administered. Change in dose of the insulin used by patients in the Lixisenatide arm (i.e. Insulin Glargine) is reported in the secondary Outcome Measure 9. |
| Time Frame | Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline total insulin dose assessment during on-treatment period. |
| Arm/Group Title | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|
| Arm/Group Description | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 295 | 294 |
| Mean (Standard Deviation) [U] |
73.61
(39.13)
|
81.05
(33.55)
|
| Title | Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia |
|---|---|
| Description | Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <60 mg/dL (3.3 mmol/L). Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the participant required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available. |
| Time Frame | First dose of study drug up to 3 days after the last dose administration (maximum of 185 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who were exposed to at least one dose of study drug, regardless of the amount of treatment administered. The 4 participants in the TID group who received Insulin Glulisine QD were analyzed according to the QD dose.The 1 participant in the QD group who received Insulin Glulisine TID was analyzed according to the TID dose |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 298 | 301 | 294 |
| Documented symptomatic hypoglycemia |
31.5
10.6%
|
37.5
12.6%
|
44.6
15%
|
| Severe symptomatic hypoglycemia |
0
0%
|
0.7
0.2%
|
0
0%
|
| Title | Percentage of Participants Who Reached the Target of HbA1c <7% at Week 26 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26 Week Treatment Period |
|---|---|
| Description | The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug. |
| Time Frame | Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Participants without any post-baseline on-treatment value for HbA1c were counted as non-responders if they experienced at least one symptomatic hypoglycemia. Otherwise, they were counted as missing. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 296 | 293 | 295 |
| Number [percentage of participants] |
29.4
9.9%
|
24.2
8.1%
|
26.1
8.8%
|
| Title | Percentage of Participants Who Reached the Target of HbA1c <7% and Had no Weight Gain at Week 26 |
|---|---|
| Description | The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. |
| Time Frame | Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population. Participants without post-baseline on-treatment values (for HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (HbA1c and/or body weight) was available and showed non-response. Otherwise, they were counted as missing data. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin. |
| Measure Participants | 295 | 293 | 295 |
| Number [percentage of participants] |
31.2
10.5%
|
16.7
5.6%
|
17.6
5.9%
|
| Title | Percentage of Participants Who Reached the Target of HbA1c <7%, Had no Weight Gain at Week 26, and Did Not Experience Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26-Week Treatment Period |
|---|---|
| Description | The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug. Participants without post-baseline on-treatment values (HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (HbA1c and/or body weight) was available and showed non-response, or if they experienced at least one documented symptomatic hypoglycemia during the on-treatment period. Otherwise, they were counted as missing data. |
| Time Frame | Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population.Participants without post-baseline on-treatment values(HbA1c;body weight),no more than 30 days apart counted as non-responders if at least one of components(HbA1c;body weight) was available,showed non-response or experienced at least one symptomatic hypoglycemia during on-treatment period.Otherwise,they were counted as missing data. |
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID |
|---|---|---|---|
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine QD SC up to Week 26 on top of insulin glargine with or without metformin. | Insulin glulisine TID SC up to Week 26 on top of insulin glargine with or without metformin. |
| Measure Participants | 297 | 294 | 295 |
| Number [percentage of participants] |
22.2
7.4%
|
9.2
3.1%
|
10.8
3.6%
|
Adverse Events
| Time Frame | All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 185) regardless of seriousness or relationship to IMP. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Analysis was done on safety population. 4 participants randomized to TID group, but received insulin glulisine QD were analyzed according to the QD dose. 1 participant randomized to QD group, but received insulin glulisine TID was analyzed according to the TID dose. | |||||
| Arm/Group Title | Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID | |||
| Arm/Group Description | Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin (Median exposure of 182 days). | Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin (Median exposure of 182 days). | Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin (Median exposure of 182 days). | |||
All Cause Mortality |
||||||
| Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/298 (3.7%) | 11/301 (3.7%) | 14/294 (4.8%) | |||
| Cardiac disorders | ||||||
| Angina pectoris | 1/298 (0.3%) | 0/301 (0%) | 1/294 (0.3%) | |||
| Angina unstable | 0/298 (0%) | 1/301 (0.3%) | 0/294 (0%) | |||
| Atrial fibrillation | 0/298 (0%) | 1/301 (0.3%) | 0/294 (0%) | |||
| Atrioventricular block complete | 0/298 (0%) | 0/301 (0%) | 1/294 (0.3%) | |||
| Cardiac failure chronic | 0/298 (0%) | 0/301 (0%) | 1/294 (0.3%) | |||
| Cardiac failure congestive | 0/298 (0%) | 0/301 (0%) | 1/294 (0.3%) | |||
| Myocardial infarction | 0/298 (0%) | 1/301 (0.3%) | 0/294 (0%) | |||
| Myocardial ischaemia | 0/298 (0%) | 0/301 (0%) | 1/294 (0.3%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Epigastric discomfort | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Gastric ulcer haemorrhage | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Hepatobiliary disorders | ||||||
| Hepatic mass | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Infections and infestations | ||||||
| Erysipelas | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Penile infection | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Septic arthritis staphylococcal | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Cellulitis | 0/298 (0%) | 1/301 (0.3%) | 1/294 (0.3%) | |||
| Injury, poisoning and procedural complications | ||||||
| Accidental overdose | 0/298 (0%) | 2/301 (0.7%) | 1/294 (0.3%) | |||
| Ankle fracture | 0/298 (0%) | 1/301 (0.3%) | 0/294 (0%) | |||
| Incisional hernia | 0/298 (0%) | 1/301 (0.3%) | 0/294 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Dehydration | 1/298 (0.3%) | 1/301 (0.3%) | 0/294 (0%) | |||
| Hypoglycaemia | 0/298 (0%) | 1/301 (0.3%) | 0/294 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Invasive ductal breast carcinoma | 1/298 (0.3%) | 0/301 (0%) | 1/294 (0.3%) | |||
| Pancreatic carcinoma metastatic | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Uterine cancer | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Basal cell carcinoma | 0/298 (0%) | 0/301 (0%) | 1/294 (0.3%) | |||
| Neoplasm malignant | 0/298 (0%) | 0/301 (0%) | 1/294 (0.3%) | |||
| Nervous system disorders | ||||||
| Cerebrovascular accident | 1/298 (0.3%) | 0/301 (0%) | 2/294 (0.7%) | |||
| Hypoglycaemic unconsciousness | 0/298 (0%) | 2/301 (0.7%) | 0/294 (0%) | |||
| Neuritis cranial | 0/298 (0%) | 1/301 (0.3%) | 0/294 (0%) | |||
| Renal and urinary disorders | ||||||
| Renal failure | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Renal failure acute | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Diabetic bullosis | 1/298 (0.3%) | 0/301 (0%) | 0/294 (0%) | |||
| Skin ulcer haemorrhage | 0/298 (0%) | 0/301 (0%) | 1/294 (0.3%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/298 (0%) | 0/301 (0%) | 1/294 (0.3%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Lixisenatide | Insulin Glulisine QD | Insulin Glulisine TID | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 183/298 (61.4%) | 186/301 (61.8%) | 195/294 (66.3%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 75/298 (25.2%) | 5/301 (1.7%) | 3/294 (1%) | |||
| Vomiting | 26/298 (8.7%) | 5/301 (1.7%) | 6/294 (2%) | |||
| Diarrhoea | 20/298 (6.7%) | 10/301 (3.3%) | 4/294 (1.4%) | |||
| Infections and infestations | ||||||
| Nasopharyngitis | 14/298 (4.7%) | 21/301 (7%) | 18/294 (6.1%) | |||
| Injury, poisoning and procedural complications | ||||||
| Accidental overdose | 0/298 (0%) | 12/301 (4%) | 20/294 (6.8%) | |||
| Investigations | ||||||
| Blood glucose decreased | 60/298 (20.1%) | 67/301 (22.3%) | 82/294 (27.9%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypoglycaemia | 107/298 (35.9%) | 140/301 (46.5%) | 154/294 (52.4%) | |||
| Nervous system disorders | ||||||
| Headache | 20/298 (6.7%) | 8/301 (2.7%) | 12/294 (4.1%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
| Name/Title | Trial Transparency Team |
|---|---|
| Organization | Sanofi |
| Phone | |
| Contact-US@sanofi.com |
Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT01768559
Other Study ID Numbers:
- EFC12626
- 2012-004096-38
- U1111-1131-4936
First Posted:
Jan 15, 2013
Last Update Posted:
Jan 4, 2017
Last Verified:
Nov 1, 2016