Type 2 Diabetes Mellitus MedDRA version: 14.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent 2. Males and females, 18 to 75 years old, inclusive 3. Documented history of T2DM 4. Receiving one of the following SU or metformin therapies in addition to diet and exercise for at least 90 days prior to Screening: a. glimepiride at a daily dose of = 2 mg and = 4 mg b. glipizide, glyburide, or glibenclamide (or equivalent) at a daily dose of = 7.5 mg c. gliclazide at a daily dose of > 160 mg (or = 60 mg for the MR formulation) d. metformin at a daily dose of = 1500 mg 5. Body mass index (BMI) 25 kg/m2 to 45 kg/m2, inclusive, at Screening 6. HbA1c 7% to 10%, inclusive, at Screening and the end of the Qualifying Period (Day 14 + 2 days) 7. Fasting serum C-peptide = 0.8 ng/mL at Screening 8. FSG = 130 mg/dL (7.2 mmol/L) and = 240 mg/dL (13.3 mmol/L) at Screening and at the end of the Qualifying Period (Day 14 + 2 days):A one-time central laboratory re-test of FSG is allowed in subjects with an initial central laboratory FSG = 120 mg/dL (6.7mmol/L) and =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1.History of or current diagnosis of type 1 DM 2.History of diabetic ketoacidosis,ketosis-prone diabetes, or hyperosmolar hyperglycemic coma 3.History of a severe episode of hypoglycemia (=1 episode within 3 months prior to Screen or =2 episodes within 6 months prior to Screen),defined as hypoglycemia requiring 3rd party assistance to actively administer carbohydrate,glucagon,or other resuscitative actions due to severe impairment in consciousness or behavior 4.Clinically significant complications of diabetes that in the judgment of the investigator would make the subject unsuitable to participate in this study 5.History of any clinically significant CV or cerebrovascular event =3 months prior to Screening 6.Inadequately controlled or unstable hypertension as defined by a SBP>160 mmHg or DBP>100 mmHg at Screen and at Randomization 7.Prolonged QTc interval >500msec by ECG at Screen,a personal or family history of QTc prolongation,congenital long QT syndrome,or subjects who are receiving drugs that prolong the QTc interval,such as Class Ia or Class III antiarrhythmic agents, erythromycin,and certain antipsychotics 8.History of bariatric surgery at any time in the past or any other surgery 3x ULN and/or ALT >3x ULN and/or serum total bilirubin >2.0 mg/dL 14.History of cancer (except non-melanomic skin cancers or cervical in situ) within 5 years prior to Screen. 15.History of alcohol or other drug abuse <12 months prior to Screen 16.Any other clinically significant existing medical or psychiatric condition, including clinically significant laboratory abnormalities,or one requiring further evaluation that in the opinion of the investigator could interfere with conduct of the study or interpretation of the data 17.Use of antihyperglycemic agents other than SU agents or metformin, including but not limited to dipeptidyl peptidase-4 inhibitors (eg, saxagliptin and sitagliptin), and glucagon-like peptide-mimetics (eg, exenatide or insulin) <3 months prior to Screen".Use of TZDs (eg, rosiglitazone or pioglitazone)<24 weeks prior to Screen. 18.Previous history of intolerance of glimepiride (as a single-agent therapy) 19.Prior treatment with open-label ranolazine,or known hypersensitivity or intolerance to ranolazine or any of its excipients 20.Treatment with strong or moderate CYP3A inhibitors or P-gp inhibitors within 14 days prior to Randomization 21.Treatment with CYP3A inducers or P-gp inducers within 14 days prior to Randomization 22.Treatment with CYP3A4 substrates with a narrow therapeutic range (eg cyclosporine, tacrolimus, or sirolimus) within 14 days prior to Randomization 23.Treatment with simvastatin at a d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to: • Determine the effect of ranolazine on hemoglobin A1c (HbA1c) after 24 weeks of treatment when added to glimepiride in subjects who have inadequately controlled type 2 diabetes mellitus (T2DM) despite current treatment with stable sulfonylurea (SU) or metformin therapy in addition to diet and exercise;Secondary Objective: The secondary objectives of the study are to: • Determine the effect of ranolazine when added to glimepiride on postprandial serum glucose (PPG) • Determine the effect of ranolazine when added to glimepiride on fasting serum glucose (FSG) The additional objectives of the study are to: • Evaluate the effect of ranolazine when added to glimepiride on each of the following parameters: serum C-peptide, serum insulin, and plasma glucagon • Evaluate the pharmacokinetics (PK) of ranolazine The safety objective of the study is to: • Evaluate the safety and tolerability of ranolazine when added to glimepiride in subjects who have inadequately controlled T2DM despite current treatment with stable SU or metformin therapy in addition to diet and exercise;Primary end point(s): The primary efficacy endpoint of this study is the following: • Change from Baseline in HbA1c at Week 24 of Treatment Period;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints of this study are the following: • Change from Baseline in incremental change of 2-hour PPG at Week 24 •Change from Baseline in FSG at Week 24 or change from Baseline in 2-hour PPG at Week 24 ;Timepoint(s) of evaluation of this end point: Week 24 | — |
Countries
Belarus, Czech Republic, Hungary, Malaysia, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Taiwan, Thailand, Ukraine, United States
Contacts
Public ContactInternational Regulatory Affairs
Gilead Sciences International Ltd
Outcome results
None listed