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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01546558
First received: February 27, 2012
Last updated: July 9, 2012
Last verified: July 2012
History of Changes
  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 Intervention Phase
Type 2 Diabetes Mellitus
 Drug: Metformin
Drug: Ranolazine
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

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 ]

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 ]

Enrollment: 25
Study Start Date: February 2012
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
 Drug: Metformin
Metformin 1000 mg bid on Days 1-10
Other Name: Glucophage
Drug: Ranolazine
Ranolazine 500 mg bid on Days 6-10
Other Name: Ranexa

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

Ages Eligible for Study:   30 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01546558

Locations
United States, Florida
SeaView Research Inc.
Miami, Florida, United States, 33126
Sponsors and Collaborators
Gilead Sciences
Investigators
Principal Investigator: Axel Juan, MD SeaView Research, Inc.
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01546558     History of Changes
Other Study ID Numbers: GS-US-259-0143
Study First Received: February 27, 2012
Last Updated: July 9, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Federal Government

Keywords provided by Gilead Sciences:
Metformin
Ranolazine
Type 2 Diabetes Mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
 Ranolazine
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013