A Study to Assess the Effects of Canagliflozin (JNJ-28431754) on the Pharmacokinetics, Pharmacodynamics, and Safety of Simvastatin in Healthy Volunteers

A Open-Label, Single Sequence Study to Assess the Pharmacokinetics and Pharmacodynamics of Simvastatin Alone and of Simvastatin in Combination With JNJ-28431754 in Healthy Adult Subjects

The purpose of this study is to determine how multiple doses of canagliflozin (JNJ-28431754) affect the pharmacokinetics (ie, how the body affects the drug) and pharmacodynamics (ie, how the drug affects the body) of a single dose of simvastatin.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Simvastatin; Drug: Canagliflozin (JNJ-28431754)

Detailed Description

This study will be an open-label (all volunteers and study staff know the identity of the assigned treatment), single-center, fixed-sequence study (all volunteers receive the same medication on the same days and in the same order) to determine how multiple doses of canagliflozin (a drug currently being investigated for the treatment of type 2 diabetes mellitus) affects the pharmacokinetics and pharmacodynamics of a single dose of simvastatin (a drug used to treat raised cholesterol). The study will consist of 3 phases: a screening phase, an open-label treatment phase, and an end-of-study (or follow-up) phase. During the open-label treatment phase, each volunteer will receive a single 40 mg dose of simvastatin on Day 1, followed by 300 mg of canagliflozin once daily on Days 2 through 6. On Day 7, volunteers will receive both simvastatin 40 mg and canagliflozin 300 mg. Each volunteer will participate in the study for approximately 32 days

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Volunteers must have a body mass index (BMI) (weight in kg/height in m2) between 18 and 30 kg/m2 (inclusive), and body weight not less than 50 kg
• Volunteers must be non-smokers

Exclusion Criteria:

- History of, or current active illness, considered to be clinically significant by the Investigator, or any other illness that the Investigator considers should exclude the patient from the study, or that could interfere with the interpretation of the study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Canagliflozin + simvastatin; Each volunteer will receive a single dose of simvastatin on Day 1, followed by canagliflozin (JNJ-28431754) once daily on Days 2 through 6. On Day 7 volunteers will receive a single dose of simvastatin in combination with a single dose of canagliflozin.	Drug: Simvastatin; One 40 mg tablet taken orally (by mouth) on Day 1 and Day 7.; Other Names: Zocor; Drug: Canagliflozin (JNJ-28431754); One 300 mg dose (ie, one 100 mg and one 200 mg over-encapsulated tablet) taken orally (by mouth) on Days 2 through Day 7.; Other Names: JNJ-28431754

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of simvastatin	Comparison of plasma concentrations of simvastatin following administration of a single dose of simvastatin alone or in combination with multiple doses of canagliflozin (JNJ-28431754). This will be used to determine whether there is a pharmacokinetic interaction between simvastatin and canagliflozin.	Up to Day 8
Plasma concentrations of the active beta-hydroxyacid metabolite of simvastatin	Comparison of plasma concentrations of the active metabolite of simvastatin following administration of a single dose of simvastatin alone or in combination with multiple doses of canagliflozin (JNJ-28431754). This will be used to determine whether there is a pharmacokinetic interaction between simvastatin and canagliflozin.	Up to Day 8
Plasma concentrations of active 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitory activity	Comparison of plasma HMG-CoA reductase inhibitory activity following administration of a single dose of simvastatin alone or in combination with multiple doses of canagliflozin (JNJ-28431754). This will be used to determine whether there is a pharmacodynamic interaction between simvastatin and canagliflozin. (Simvastatin lowers cholesterol by inhibiting the activity of the enzyme HMG-CoA reductase).	Up to Day 8

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications and helpful links

General Publications

• Devineni D, Manitpisitkul P, Murphy J, Skee D, Wajs E, Mamidi RN, Tian H, Vandebosch A, Wang SS, Verhaeghe T, Stieltjes H, Usiskin K. Effect of canagliflozin on the pharmacokinetics of glyburide, metformin, and simvastatin in healthy participants. Clin Pharmacol Drug Dev. 2015 May-Jun;4(3):226-36. doi: 10.1002/cpdd.166. Epub 2014 Oct 27.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: March 26, 2013
• First Submitted That Met QC Criteria: March 26, 2013
• First Posted (Estimate): March 29, 2013

Study Record Updates

• Last Update Posted (Estimate): March 29, 2013
• Last Update Submitted That Met QC Criteria: March 26, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Healthy; Pharmacokinetics; Pharmacodynamics; Canagliflozin (JNJ-28431754); Simvastatin (ZOCOR)
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Simvastatin; Canagliflozin
• Other Study ID Numbers: CR015511; 28431754DIA1009 (Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)