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

• ClinicalTrials.gov Identifier: NCT01733108
• Recruitment Status: Completed
• First Posted: November 26, 2012
• Last Update Posted: December 12, 2012
• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Information provided by (Responsible Party): Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Tracking Information

• First Submitted Date: November 20, 2012
• First Posted Date: November 26, 2012
• Last Update Posted Date: December 12, 2012
• Study Start Date: July 2008
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 20, 2012)

• Plasma concentrations of glyburide [ Time Frame: Up to Day 12 ]
  Comparison of plasma concentrations of glyburide following administration of a single dose of glyburide alone or in combination with multiple doses of canagliflozin (JNJ-28431754). This will be used to determine whether there is a pharmacokinetic interaction between glyburide and canagliflozin.
• Plasma concentrations of glyburide metabolites [ Time Frame: Up to Day 12 ]
  Comparison of plasma concentrations of glyburide metabolites following administration of a single dose of glyburide alone or in combination with multiple doses of canagliflozin (JNJ-28431754). This will be used to determine whether there is a pharmacokinetic interaction between glyburide and canagliflozin.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 20, 2012)

• Change from baseline in plasma glucose concentrations [ Time Frame: Day -1 (Baseline) up to Day 9 ]
  Plasma glucose concentrations following the administration of a single dose of glyburide after the administration of multiple doses of canagliflozin (JNJ-28431754) will be used to determine whether there is a pharmacodynamic interaction (changes in plasma glucose) between glyburide and canagliflozin. The area under the plasma glucose concentration-time curve (AUC) will be used as the key pharmacodynamic parameter.
• Change from baseline in plasma insulin concentrations [ Time Frame: Day -1 (Baseline) up to Day 9 ]
  Plasma insulin concentrations following the administration of a single dose of glyburide after the administration of multiple doses of canagliflozin (JNJ-28431754) will be used to determine whether there is a pharmacodynamic interaction (changes to plasma insulin) between glyburide and canagliflozin. The area under the plasma insulin concentration-time curve (AUC) will be used as the key pharmacodynamic parameter.
• Change from baseline in plasma C-peptide concentrations [ Time Frame: Day -1 (Baseline) up to Day 9 ]
  Plasma C-peptide is formed during the body's production of insulin. Plasma C-peptide concentrations following the administration of a single dose of glyburide after the administration of multiple doses of canagliflozin (JNJ-28431754) will be used to determine whether there is a pharmacodynamic interaction (changes to plasma C-peptide) between glyburide and canaglifloxin. The area under the plasma C-peptide concentration-time curve (AUC) will be used as the key pharmacodynamic parameter.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess the Effects of Canagliflozin (JNJ-28431754) on the Pharmacokinetics, Pharmacodynamics, and Safety of Glyburide in Healthy Volunteers
• Official Title: An Open-Label Drug-Drug Interaction Study in Healthy Subjects to Explore the Effects of Multiple Doses of JNJ-28431754 on the Pharmacokinetics and Safety of Single Doses of Glyburide
• Brief Summary: 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 glyburide.
• 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 and pharmacodynamics of glyburide (a blood glucose-lowering agent used to treat patients with diabetes). 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 1.25 mg dose of glyburide on Day 1, followed by 200 mg canagliflozin once daily on Days 4 through 8. On Day 9 volunteers will receive both glyburide 1.25 mg and canagliflozin 200 mg. Each volunteer will participate in the study for approximately 40 days.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Healthy

Intervention

• Drug: Glyburide
  One 1.25 mg tablet taken orally (by mouth) on Day 1 and Day 9.
  Other Name: Micronase
• Drug: Canagliflozin (JNJ-28431754)
  One 200 mg tablet taken orally (by mouth) on Days 4 through 9.
  Other Name: JNJ-28431754

Study Arms

Experimental: Canagliflozin (JNJ-28431754) + glyburide

Each volunteer will receive a single dose of glyburide 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 glyburide in combination with a single dose of canagliflozin.

Interventions:

• Drug: Glyburide
• Drug: Canagliflozin (JNJ-28431754)

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 20, 2012): 29
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: September 2008
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Volunteer 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:
• Volunteer has a 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
• Volunteer has a fasting plasma glucose < 100 mg/dL (as measured by oral glucose tolerance test) and a 2-hour plasma glucose <= 140 mg/dL
• History of smoking or use of nicotine-containing substances within the previous 6 months

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT01733108
• Other Study ID Numbers: CR014872; 28431754DIA1004 ( Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Study Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Collaborators: Not Provided

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

• PRS Account: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Verification Date: December 2012