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

An Open-Label, 2-Period, Crossover Study to Evaluate the Effects of Multiple Doses of JNJ-28431754 on the Pharmacokinetics of Multiple Doses of Digoxin in Healthy 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) of multiple doses of digoxin. The safety and tolerability of canagliflozin will also be assessed in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Digoxin 0.5 mg; Drug: Digoxin 0.25 mg; 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), randomized (the treatment is assigned by chance), multiple dose, cross-over study (all volunteers will switch from one treatment to another) to determine how canagliflozin (a drug currently being investigated for the treatment of type 2 diabetes mellitus) affects the pharmacokinetics of digoxin (a drug used to treat various heart conditions). Volunteers will be randomly assigned to 1 of 2 treatment sequence groups: Group AB or Group BA. Volunteers assigned to Group AB will be given Treatment A: digoxin once a day for 7 days. Volunteers assigned to Group BA will be given Treatment B: digoxin and canagliflozin once a day for 7 days. A washout period (when no medication is given) of at least 14 days will follow the first 7-day treatment period. Following the washout period, volunteers will be assigned to the treatment that they did not receive during the first treatment period. This second treatment period will last for 7 days. Each volunteer will participate in the study for approximately 60 days.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 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
• 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: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A; Each volunteer will receive digoxin once daily on Days 1 through 7.	Drug: Digoxin 0.5 mg; Two 0.25 mg tablets (0.5 mg total dose) taken orally (by mouth) on Day 1.; Other Names: Lanoxin; Drug: Digoxin 0.25 mg; One 0.25 mg tablet taken orally on Days 2 through 7.; Other Names: Lanoxin
Experimental: Treatment B; Each volunteer will receive digoxin once daily on Days 1 through 7 in combination with canagliflozin (JNJ-28431754) once daily on Days 1 through 7.	Drug: Digoxin 0.5 mg; Two 0.25 mg tablets (0.5 mg total dose) taken orally (by mouth) on Day 1.; Other Names: Lanoxin; Drug: Digoxin 0.25 mg; One 0.25 mg tablet taken orally on Days 2 through 7.; Other Names: Lanoxin; Drug: Canagliflozin (JNJ-28431754); One 300 mg tablet taken orally on Days 1 through 7.; Other Names: JNJ-28431754

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of digoxin	Comparison of plasma concentrations of digoxin following administration of digoxin alone (Treatment A) or in combination with canagliflozin (JNJ-28431754) (Treatment B). This will be used to determine whether there is a pharmacokinetic interaction between digoxin and canagliflozin.	Days 5 through 7
Urine concentration of digoxin	Comparison of the urine concentrations of digoxin following administration of digoxin alone (Treatment A) or in combination with canagliflozin (JNJ-28431754) (Treatment B). This will be used to determine whether there is a pharmacokinetic interaction between canagliflozin and digoxin.	Day 7

Secondary Outcome Measures

Outcome Measure
There are no secondary outcome measures

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Devineni D, Manitpisitkul P, Vaccaro N, Bernard A, Skee D, Mamidi RN, Tian H, Weiner S, Stieltjes H, Sha S, Rothenberg P. Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on the pharmacokinetics of oral contraceptives, warfarin, and digoxin in healthy participants. Int J Clin Pharmacol Ther. 2015 Jan;53(1):41-53. doi: 10.5414/CP202157.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: October 23, 2012
• First Submitted That Met QC Criteria: October 24, 2012
• First Posted (Estimate): October 25, 2012

Study Record Updates

• Last Update Posted (Estimate): November 19, 2012
• Last Update Submitted That Met QC Criteria: November 16, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Healthy; Pharmacokinetics; Canagliflozin (JNJ-28431754); Digoxin (LANOXIN)
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Sodium-Glucose Transporter 2 Inhibitors; Digoxin; Canagliflozin
• Other Study ID Numbers: CR016465; 28431754DIA1014 (Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)