Single Cohort, 2-Period Study to Assess Pharmacokinetics of Metformin Alone and in Combination With Ranolazine 500 mg | RxWiki

Single Cohort, 2-Period Study to Assess Pharmacokinetics of Metformin Alone and in Combination With Ranolazine 500 mg

Overview[ - collapse ][ - ]

Purpose	The purpose of this study is to evaluate the effect of steady-state ranolazine 500 mg bid on the steady state pharmacokinetics (PK) of metformin in subjects with type 2 diabetes mellitus (T2DM).
Condition	Type 2 Diabetes Mellitus
Intervention	Drug: Metformin Drug: Ranolazine
Phase	Phase 1
Sponsor	Gilead Sciences
Responsible Party	Gilead Sciences
ClinicalTrials.gov Identifier	NCT01546558
First Received	February 27, 2012
Last Updated	July 9, 2012
Last verified	July 2012

Tracking Information[ + expand ][ + ]

First Received Date	February 27, 2012
Last Updated Date	July 9, 2012
Start Date	February 2012
Estimated Primary Completion Date	March 2012
Current Primary Outcome Measures	Maximum observed plasma concentration (Cmax) of metformin [Time Frame: 0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 5 and 10] [Designated as safety issue: No] Area under the plasma concentration vs time curve over the dosing interval, at steady state (AUCtau) of metformin [Time Frame: 0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 5 and 10] [Designated as safety issue: No]
Current Secondary Outcome Measures	Number of participants with adverse events [Time Frame: From time of signed informed consent to time of follow-up phone call, an expected average of 5 weeks] [Designated as safety issue: Yes] Maximum observed plasma concentration (Cmax) of ranolazine and metabolites [Time Frame: 0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Day 10] [Designated as safety issue: No] Area under the plasma concentration versus time curve over the dosing interval, at steady state (AUCtau) of ranolazine and metabolites [Time Frame: 0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Day 10] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief Title	Single Cohort, 2-Period Study to Assess Pharmacokinetics of Metformin Alone and in Combination With Ranolazine 500 mg
Official Title	A Phase 1, Open-label, Single Cohort, Two-Period Fixed Sequence Study to Assess the Pharmacokinetics of Metformin Alone and in Combination With Ranolazine 500 mg Twice Daily in Subjects With Type 2 Diabetes Mellitus
Brief Summary	The purpose of this study is to evaluate the effect of steady-state ranolazine 500 mg bid on the steady state pharmacokinetics (PK) of metformin in subjects with type 2 diabetes mellitus (T2DM).
Detailed Description	The primary objective of this study is as follows: • To evaluate the effect of steady-state ranolazine 500 mg twice daily (bid) on the steady state pharmacokinetics (PK) of metformin in subjects with T2DM. The secondary objectives of this study are as follows: - To examine the safety and tolerability of metformin when co administered with ranolazine 500 mg bid at steady-state in subjects with T2DM. - To determine the steady-state PK of ranolazine 500 mg bid in subjects with T2DM receiving metformin.
Study Type	Interventional
Study Phase	Phase 1
Study Design	Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label
Condition	Type 2 Diabetes Mellitus
Intervention	Drug: Metformin Metformin 1000 mg bid on Days 1-10 Other Names: GlucophageDrug: Ranolazine Ranolazine 500 mg bid on Days 6-10 Other Names: Ranexa
Study Arm (s)	Experimental: Metformin, Ranolazine Single cohort, 2-period study: Period 1, metformin 1000 mg bid on Days 1-5 Period 2, metformin 1000 mg bid + ranolazine 500 mg bid on Days 6-10

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	25
Estimated Completion Date	March 2012
Estimated Primary Completion Date	March 2012
Eligibility Criteria	Inclusion Criteria: - Males and females, 30 to 65 years old, inclusive - Documented history of T2DM - HbA1c 6.5%-10%, inclusive - Fasting serum glucose ≤ 270 mg/dL at Screening - Fasting C-peptide ≥ 1 ng/mL at Screening - Stable metformin monotherapy (metformin ≥ 1500 mg total daily dose for at least 4 weeks prior to Screening) - Body mass index (BMI) 25 to 40 kg/m2, inclusive, at Screening - Creatinine Clearance > 80 mL/min at Screening - Females of child-bearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1 and must agree to use highly effective contraception methods from Screening throughout the duration of the Treatment Period and for 14 days following the last dose of study drug Exclusion Criteria: - Type 1 Diabetes Mellitus (T1DM) - Use of insulin therapy < 3 months prior to Screening - History of ketoacidosis, ketosis-prone diabetes, or lactic acidosis - Clinically significant complications of diabetes - History of hypoglycemia - Any non-insulin antidiabetic therapy (other than metformin) < 2 months prior to Screening - Any clinically significant cardiovascular event < 2 months prior to Screening - Clinically significant, inadequately controlled, or unstable hypertension - Hospitalization < 2 months prior to Screening or major surgery < 3 months prior to Screening - History of gastrointestinal disease or surgery that could impact drug absorption - History of substance of alcohol or substance abuse - Positive urine drug screen for drugs of abuse - Positive alcohol breath test - Any other clinically significant existing medical or psychiatric condition or one requiring further evaluation - Treatment with selected medications - Hemoglobin < 12 g/dL for males; or < 11 g/dL for females at Screening - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5x upper limits of normal - Clinically significant history of hepatic disease or evidence of hepatic impairment - Positive blood screen for hepatitis C or hepatitis B - QTc interval > 500 msec at Screening - Females who are pregnant or are breastfeeding
Gender	Both
Ages	30 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01546558
Other Study ID Numbers	GS-US-259-0143
Has Data Monitoring Committee	No
Information Provided By	Gilead Sciences
Study Sponsor	Gilead Sciences
Collaborators	Not Provided
Investigators	Principal Investigator: Axel Juan, MD SeaView Research, Inc.
Verification Date	July 2012

Locations[ + expand ][ + ]