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

An Open-label Drug-Drug Interaction Study in Healthy Female Subjects to Explore the Effects of Multiple Doses of JNJ-28431754 on the Pharmacokinetics and Safety of Single Doses of an Oral Contraceptive Containing Ethinyl Estradiol and Levonorgestrel

The purpose of this study is to investigate whether there is a drug-drug interaction between multiple doses of canagliflozin (JNJ-28431754) and single doses of an oral contraceptive containing ethinyl estradiol and levonorgestrel. The safety and tolerability of canagliflozin will also be assessed in healthy volunteers.

Study Overview

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

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), to determine how canagliflozin (a drug currently being investigated for the treatment of type 2 diabetes mellitus) affects the pharmacokinetics (ie, how the body affects the drug) of an oral contraceptive containing ethinyl estradiol and levonorgestrel. The study will consist of 3 phases; a screening phase, an open-label treatment phase, and an end-of-study (or follow-up) phase. Each volunteer will participate in the study for approximately 33 days.

• Study Type: Interventional
• Enrollment (Actual): 30
• 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: Female

Description

Inclusion Criteria:

• Volunteer must have a body mass index (weight [kg]/height [m2]) between 18 and 30 kg/m2 (inclusive), and body weight not less than 50 kg
• Volunteer must be a non-smoker (has not used tobacco or nicotine products in 6 months)

Exclusion Criteria:

• History of or currently 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
• History of, or presence of, disorders commonly accepted as contraindications to sex hormonal therapy and contraindications to therapy with combined oral contraceptives
• Volunteer has used, or is currently using, any hormonal contraceptive within 30 days of admission to the study center or has received Depo Provera (or other combined contraceptive injection or hormonal contraceptive implant) in the 6 months prior to screening
• Volunteer is breast-feeding

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 + oral contraceptive; Each volunteer will receive a single dose of an oral contraceptive containing ethinyl estradiol and levonorgestrel on Day 1, followed by canagliflozin (JNJ-28431754) once daily on Days 4 through 8. On Day 9 volunteers will receive a single dose of an oral contraceptive containing ethinyl estradiol and levonorgestrel in combination with a single dose of canagliflozin.

Drug: Canagliflozin (JNJ-28431754); One 200 mg tablet taken orally (by mouth) on Days 4 through 9.; Other Names: JNJ-28431754; Drug: Oral contraceptive; One tablet (0.150 mg of levonorgestrel and 0.030 mg of ethinyl estradiol) taken orally (by mouth) on Day 1 and Day 9.; Other Names: Levora

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of ethinyl estradiol and levonorgestrel	Comparison of plasma concentrations of ethinyl estradiol and levonorgestrel, before and after administration of multiple doses of canagliflozin (JNJ-28431754). This will be used to determine whether there is a pharmacokinetic interaction between multiple doses of canagliflozin and single doses of an oral contraceptive containing ethinyl estradiol and levonorgestrel.	Up to Day 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of canagliflozin (JNJ-28431754)	Comparison of plasma concentrations of canagliflozin (JNJ-28431754) before and after administration of a single dose of an oral contraceptive containing ethinyl estradiol and levonorgestrel. This will be used to determine whether there is a pharmacokinetic interaction between multiple doses of canagliflozin and single doses of an oral contraceptive containing ethinyl estradiol and levonorgestrel.	Days 8 and 9

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: February 1, 2008
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: October 23, 2012
• First Submitted That Met QC Criteria: October 23, 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; Levonorgestrel; Ethinyl Estradiol; Canagliflozin (JNJ-28431754); Contraceptives, Oral; LEVORA
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Reproductive Control Agents; Contraceptive Agents, Female; Sodium-Glucose Transporter 2 Inhibitors; Contraceptive Agents; Contraceptives, Oral; Canagliflozin
• Other Study ID Numbers: CR014755; 28431754DIA1002 (Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)