24-week Treatment With Lixisenatide in Type 2 Diabetes Insufficiently Controlled With Metformin and Insulin Glargine
Overview[ - collapse ][ - ]
| Purpose | The primary objective of this study is to assess the effects on glycemic control of lixisenatide in comparison to placebo as an add-on treatment to insulin glargine and metformin over a period of 24 weeks. The secondary objectives are : - To assess the effects of lixisenatide on the percentage of patients reaching HbA1c <7 % and < or = 6.5 %, on plasma glucose (fasting, post-prandial during a standardized meal challenge test, 7-point self monitored profiles), body weight, insulin glargine doses. - To evaluate lixisenatide safety and tolerability as add on treatment to insulin glargine and metformin. - To assess the impact of lixisenatide on treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (state) (DTSQs) in the participating countries where it is validated. |
|---|---|
| Condition | Type 2 Diabetes Mellitus |
| Intervention | Drug: lixisenatide (AVE0010) Drug: placebo Drug: insulin glargine (HOE901) Drug: metformin |
| Phase | Phase 3 |
| Sponsor | Sanofi |
| Responsible Party | Sanofi |
| ClinicalTrials.gov Identifier | NCT00975286 |
| First Received | September 10, 2009 |
| Last Updated | May 7, 2012 |
| Last verified | May 2012 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 10, 2009 |
|---|---|
| Last Updated Date | May 7, 2012 |
| Start Date | October 2009 |
| Estimated Primary Completion Date | August 2011 |
| Current Primary Outcome Measures | Change from baseline in glycated hemoglobin (HbA1c) [Time Frame: 24 weeks] [Designated as safety issue: No] |
| Current Secondary Outcome Measures |
|
Descriptive Information[ + expand ][ + ]
| Brief Title | 24-week Treatment With Lixisenatide in Type 2 Diabetes Insufficiently Controlled With Metformin and Insulin Glargine |
|---|---|
| Official Title | A Randomized, Placebo-controlled, 2-arm Parallel-group, Multicenter Study With a 24-week Double-blind Treatment Period Assessing the Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Insufficiently Controlled With Insulin Glargine and Metformin |
| Brief Summary | The primary objective of this study is to assess the effects on glycemic control of lixisenatide in comparison to placebo as an add-on treatment to insulin glargine and metformin over a period of 24 weeks. The secondary objectives are : - To assess the effects of lixisenatide on the percentage of patients reaching HbA1c <7 % and < or = 6.5 %, on plasma glucose (fasting, post-prandial during a standardized meal challenge test, 7-point self monitored profiles), body weight, insulin glargine doses. - To evaluate lixisenatide safety and tolerability as add on treatment to insulin glargine and metformin. - To assess the impact of lixisenatide on treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (state) (DTSQs) in the participating countries where it is validated. |
| Detailed Description | The study will comprise 3 periods: - An up-to 14-week screening period, which includes an up to 2-week screening phase and a 12-week run-in phase with introduction and titration of insulin glargine on top of metformin +/-TZDs. - At the end of the run-in phase, patients whose HbA1c (centralized assay) is > or = 7% and < or = 9% and whose mean fasting SMPG calculated from the self measurements for the 7 days prior to visit 12 (week -1) is less than or equal to 140 mg/dl (7.8 mmol/l), will enter a 24-week double-blind randomized treatment period comparing lixisenatide to placebo (on top of insulin glargine + metformin +/-TZDs). - A 3 day-safety follow up period. Maximum duration of 39 weeks ± 7 days |
| Study Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
| Condition | Type 2 Diabetes Mellitus |
| Intervention | Drug: lixisenatide (AVE0010) solution for subcutaneous injection Drug: placebo solution for subcutaneous injection Drug: insulin glargine (HOE901) solution for subcutaneous injection Drug: metformin continued at a stable dose throughout the study |
| Study Arm (s) |
|
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Completed |
|---|---|
| Estimated Enrollment | 446 |
| Estimated Completion Date | August 2011 |
| Estimated Primary Completion Date | August 2011 |
| Eligibility Criteria | Inclusion criteria: At screening: - Patients with type 2 diabetes mellitus, as defined by WHO (fasting plasma glucose > or = 7 mmol/L (126mg/dL) or 2 hours postprandial plasma glucose > or = 11.1 mmol/L (200 mg/dL), diagnosed at least 1 year before the screening visit - For at least 3 months: treatment with a stable dose of metformin > or = 1.5 g/day or combination of stable doses of metformin > or = 1.5 g/day with sulfonylureas (SUs) (to be stopped at the run-in visit (V2)) and/or Thiazolidinediones (TZDs) - Glycated hemoglobin (HbA1c) > or = 7.0 and < or = 10% At the end of the run in phase and before randomization: - HbA1c > or = 7.0 and < or = 9% - Mean fasting Self Monitored Plasma Glucose (SMPG) calculated from the self measurements for the 7 days prior to visit 12 (week -1) is less than or equal to 140 mg/dll (7.8 mmol/l) Exclusion criteria: At screening: - Pregnancy or lactation - Women of childbearing potential with no effective contraceptive method. - Type 1 diabetes mellitus - Metformin not at a stable dose of at least 1.5 g/day for at least 3 months prior to the screening visit. - Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin, sulfonylurea and thiazolidinediones within 3 months prior to the time of screening, use of weight loss drugs if not at a stable dose for at least 3 months prior to the screening visit. - History of hypoglycemia unawareness. - History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease - History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening - Hemoglobinopathy or hemolytic anemia, blood or plasma products transfusion within 3 months prior to the time of screening - Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization - Known history of drug or alcohol abuse within 6 months prior to the time of screening - Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure > 180 mmHg or > 110 mmHg, respectively - Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening - Use of any investigational drug within 3 months prior to screening - Renal impairment defined with serum creatinine > 1.4 mg/dL in women and > 1.5 mg/dL in men - History of hypersensitivity to insulin glargine or to any of the excipients - Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (i.e worsening) and not controlled (i.e prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening - Any previous treatment with lixisenatide (e.g. participation in a previous study with lixisenatide) - Allergic reaction to any GLP-1 receptor agonist in the past (e.g. exenatide, liraglutide) or to metacresol Additional exclusion criteria during or at the end of the run-in phase before randomization : - Informed consent withdrawal (patient who is not willing to continue or fails to return) - Mean fasting SMPG calculated from the self-measurements for the 7 days prior to visit 12 (week -1) is > 140 mg/dl (7.8 mmol/l) - HbA1c measured at visit 12 (week -1) is < 7% or > 9 %, - Amylase and/or lipase > 3 times the upper limit of the normal laboratory range at visit 12 (week -1) The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States, Argentina, Brazil, Canada, Chile, Colombia, Czech Republic, Denmark, Estonia, France, Germany, Hungary, India, Israel, Italy, Malaysia, Mexico, Netherlands, Poland, Romania, Russian Federation, South Africa, Sweden, Taiwan, Ukraine |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00975286 |
|---|---|
| Other Study ID Numbers | EFC10781 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | Sanofi |
| Study Sponsor | Sanofi |
| Collaborators | Not Provided |
| Investigators | Study Director: Clinical Study Operations Sanofi |
| Verification Date | May 2012 |
Locations[ + expand ][ + ]
| Sanofi-Aventis Investigational Site Number 840223 | Mesa, Arizona, United States, 85206 |
|---|---|
| Sanofi-Aventis Investigational Site Number 840206 | Hot Springs, Arkansas, United States, 71913 |
| Sanofi-Aventis Investigational Site Number 840201 | Little Rock, Arkansas, United States, 72205 |
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| Sanofi-Aventis Investigational Site Number 804204 | Vinnytsya, Ukraine, 21010 |