Clinical trial NCT01759576: A Study to Assess the Pharmacokinetics, Pharmacodynamics, and Safety of Canagliflozin (JNJ-28431754) in Volunteers With Varying Degrees of Kidney Function
Official title: An Open-Label, Single-Dose Study to Evaluate JNJ-28431754 Pharmacokinetics, Pharmacodynamics and Safety in Non-Diabetic Subjects With Varying Degrees of Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Insufficiency
Healthy
Keywords: Renal Insufficiency
Healthy
Canagliflozin (JNJ-28431754)
Pharmacokinetics
Pharmacodynamics
Dialysis
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2013-01-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the pharmacokinetics (ie, how the body affects the drug) and pharmacodynamics (ie, how the drug affects the body) of canagliflozin (JNJ-28431754) after administration of a single dose to non-diabetic volunteers with normal kidney function and non-diabetic volunteers with varying degrees of kidney impairment (including volunteers with end-stage renal disease requiring hemodialysis).

Detailed description: This study will be an open label (all volunteers and study staff know the identity of the assigned treatment), single-dose, multicenter (the study will be conducted at more than one center), parallel-group study (each group of volunteers will be treated at the same time) to assess the pharmacokinetics and pharmacodynamics of canagliflozin (a drug currently being investigated for the treatment of type 2 diabetes mellitus) in volunteers with varying degrees of kidney function. The study will consist of 3 phases: a screening phase, an open-label treatment phase, and an end-of study (or follow-up) phase. Volunteers will be assigned to 1 of 5 groups (depending on kidney function): group 1 will have normal kidney function; group 2 will have mild kidney impairment; group 3 will have moderate kidney impairment; group 4 will have severe kidney impairment; and group 5 will comprise volunteers requiring hemodialysis. Volunteers in groups 1 through 4 will receive a single dose of canagliflozin on Day 1. Volunteers in group 5 will receive a single dose of canagliflozin following dialysis and then, approximately 10 days later, they will receive a second dose before dialysis. Volunteers in groups 1 through 4 will participate in the study for 27 days. Volunteers in group 5 will participate in the study for 40 days.

Eligibility criteria: Inclusion Criteria:

* Volunteers must have a body mass index (BMI = weight in kg/height in m2) between 20 and 40 kg/m2 (inclusive), and body weight not less than 50 kg
* Volunteers must smoke no more than 10 cigarettes, or 2 cigars, or 2 pipes of tobacco per day for at least 6 months before first study drug administration

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
* Volunteers with end stage renal disease receiving dialysis treatment other than intermittent hemodialysis
* Volunteers with end stage renal disease who have received a renal transplantation within 1 year before screening
* Volunteers with end stage renal disease diagnosed with renal carcinoma within 1 year before screening
* Volunteers with end stage renal disease receiving immunosuppressive medications, including steroids

Primary outcomes:
measure: Plasma concentrations of canagliflozin (JNJ-28431754) in varying degrees of kidney function
timeFrame: Up to Day 6
measure: Change from baseline in 24-hour urine glucose excretion in varying degrees of kidney function
timeFrame: Day -1 (Baseline) to Day 3
measure: Plasma concentrations of canagliflozin (JNJ-28431754) metabolites in varying degrees of kidney function
timeFrame: Up to Day 6
Secondary outcomes:
Other outcomes:
Locations:
city: Orlando
country: United States
state: Florida
city: Minneapolis
country: United States
state: Minnesota
city: Knoxville
country: United States
state: Tennessee
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Devineni D, Curtin CR, Marbury TC, Smith W, Vaccaro N, Wexler D, Vandebosch A, Rusch S, Stieltjes H, Wajs E. Effect of hepatic or renal impairment on the pharmacokinetics of canagliflozin, a sodium glucose co-transporter 2 inhibitor. Clin Ther. 2015 Mar 1;37(3):610-628.e4. doi: 10.1016/j.clinthera.2014.12.013. Epub 2015 Feb 3.