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

NCT01546597 | Completed Phase 1

• 1 other identifier: GS-US-259-0137
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

Type 2 Diabetes Mellitus

Keywords

Metformin; Ranolazine; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• Maximum observed plasma concentration (Cmax) of metformin

  0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 5, 10, 15 and 20

• Time to reach maximum observed plasma concentration (Cmax) of metformin

  0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 5, 10, 15 and 20

• Area under the plasma concentration versus time curve over the dosing interval, at steady state (AUCtau) of metformin

  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 Outcomes (4)

• Number of participants with adverse events

  participants will be followed upon signing informed consent until the follow-up phone call, an expected average of 7 weeks

• Maximum observed plasma concentration (Cmax) of ranolazine and metabolites

  0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 15 and 20

• Time to reach maximum observed plasma concentration (Cmax) of ranolazine and metabolites

  0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 15 and 20

• Area under the plasma concentration versus time curve over the dosing interval, at steady state (AUCtau) of ranolazine and metabolites

  0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 15 and 20

Study Arms (1)

Metformin, Ranolazine

EXPERIMENTAL

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; Drug: Ranolazine

Interventions

Metformin DRUG

* 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

Also known as: Glucophase

Metformin, Ranolazine

Ranolazine DRUG

* Ranolazine 1000 mg bid on Days 11-15 * Ranolazine 1000 mg bid on Days 16-20

Also known as: Ranexa

Metformin, Ranolazine

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Cetero Research

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin; Ranolazine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2012
• First Posted: March 7, 2012
• Study Start: February 1, 2012
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: July 11, 2012

Record last verified: 2012-07

Locations

US (1)