Single Cohort 4-period Study to Assess Pharmacokinetics of Metformin Alone and in Combination With Ranolazine | RxWiki

Single Cohort 4-period Study to Assess Pharmacokinetics of Metformin Alone and in Combination With Ranolazine

Overview[ - collapse ][ - ]

Purpose	The purpose of this study is to evaluate the effect of steady-state ranolazine on the steady state 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	NCT01546597
First Received	February 14, 2012
Last Updated	July 9, 2012
Last verified	July 2012

Tracking Information[ + expand ][ + ]

First Received Date	February 14, 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, 10, 15 and 20] [Designated as safety issue: No] Time to reach 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, 10, 15 and 20] [Designated as safety issue: No] Area under the plasma concentration versus 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, 10, 15 and 20] [Designated as safety issue: No]
Current Secondary Outcome Measures	Number of participants with adverse events [Time Frame: participants will be followed upon signing informed consent until the follow-up phone call, an expected average of 7 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 Days 15 and 20] [Designated as safety issue: No] Time to reach 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 Days 15 and 20] [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 Days 15 and 20] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief Title	Single Cohort 4-period Study to Assess Pharmacokinetics of Metformin Alone and in Combination With Ranolazine
Official Title	A Phase 1, Open-Label, Single Cohort, Four-period Sequential Study to Assess the Pharmacokinetics of Metformin Alone and in Combination With Ranolazine in Subjects With Type 2 Diabetes Mellitus
Brief Summary	The purpose of this study is to evaluate the effect of steady-state ranolazine on the steady state 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 on the steady state 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 at steady-state in subjects with T2DM. - To determine the steady-state PK of ranolazine 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 500 mg bid on Days 1-5 Metformin 850 mg bid on Days 6-10 Metformin 500 mg bid on Days 11-15 Metformin 850 mg bid on Days 16-20 Other Names: GlucophaseDrug: Ranolazine Ranolazine 1000 mg bid on Days 11-15 Ranolazine 1000 mg bid on Days 16-20 Other Names: Ranexa
Study Arm (s)	Experimental: Metformin, Ranolazine Single cohort, 4-period study: Period 1, metformin 500 mg bid on Days 1-5 Period 2, metformin 850 mg bid on Days 6-10 Period 3, metformin 500 mg bid + ranolazine 1000 mg bid on Days 11-15 Period 4, metformin 850 mg bid + ranolazine 1000 mg bid on Days 16-20

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	24
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 1000 to 2000 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 - Active thyroid disease (hypo- or hyperthyroidism) - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5x upper limits of normal - 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	NCT01546597
Other Study ID Numbers	GS-US-259-0137
Has Data Monitoring Committee	No
Information Provided By	Gilead Sciences
Study Sponsor	Gilead Sciences
Collaborators	Not Provided
Investigators	Not Provided
Verification Date	July 2012

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