Clinical trial NCT01546558: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: Metformin
Ranolazine
Type 2 Diabetes Mellitus
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2012-03-07
Enrollment: 25
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

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.

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

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax) of metformin
timeFrame: 0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 5 and 10
measure: Area under the plasma concentration vs time curve over the dosing interval, at steady state (AUCtau) of metformin
timeFrame: 0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 5 and 10
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: From time of signed informed consent to time of follow-up phone call, an expected average of 5 weeks
measure: Maximum observed plasma concentration (Cmax) of ranolazine and metabolites
timeFrame: 0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Day 10
measure: Area under the plasma concentration versus time curve over the dosing interval, at steady state (AUCtau) of ranolazine and metabolites
timeFrame: 0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Day 10
Other outcomes:
Locations:
city: Miami
country: United States
facility: SeaView Research Inc.
state: Florida
Study officials:
affiliation: SeaView Research, Inc.
name: Axel Juan, MD
role: PRINCIPAL_INVESTIGATOR
References: