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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01546597
First received: February 14, 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 on the steady state 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, Four-period Sequential Study to Assess the Pharmacokinetics of Metformin Alone and in Combination With Ranolazine 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, 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 ]

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 ]

Enrollment: 24
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, 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
 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 Name: Glucophase
Drug: Ranolazine
  • Ranolazine 1000 mg bid on Days 11-15
  • Ranolazine 1000 mg bid on Days 16-20
Other Name: Ranexa

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.
  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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01546597

Locations
United States, Texas
Cetero Research
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01546597     History of Changes
Other Study ID Numbers: GS-US-259-0137
Study First Received: February 14, 2012
Last Updated: July 9, 2012
Health Authority: United States: Food and Drug Administration

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