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

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ClinicalTrials.gov Identifier: NCT01546597
Recruitment Status : Completed
First Posted : March 7, 2012
Last Update Posted : July 11, 2012
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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).

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Metformin Drug: Ranolazine Phase 1

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  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : February 2012
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]


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Ages Eligible for Study:   30 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01546597


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

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01546597     History of Changes
Other Study ID Numbers: GS-US-259-0137
First Posted: March 7, 2012    Key Record Dates
Last Update Posted: July 11, 2012
Last Verified: July 2012

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
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action