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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01546597
• Other study ID #: GS-US-259-0137
• Status: Completed
• Phase: Phase 1
• First received: February 14, 2012
• Last updated: July 9, 2012
• Start date: February 2012
• Est. completion date: March 2012

Study information

• Verified date: July 2012
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

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

Locations

Country	Name	City	State
United States	Cetero Research	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No