Healthy
Conditions
Keywords
Healthy, Clearance, Canagliflozin, JNJ-28431754, Placebo, Somatostatin, C-peptide
Brief summary
The purpose of this study is to assess whether treatment with a single oral 300 mg dose of canagliflozin alters the kinetics (ie, clearance/removal from body) of serum C-peptide (a protein released from the pancreas during insulin secretion) in healthy adult volunteers.
Detailed description
This is a double-blind (neither the volunteer nor the study doctor/staff will know the identity of the assigned treatments) study to assess the effect of single oral (taken by mouth) dose of canagliflozin on clearance (removal from the body) of C-peptide in healthy adult volunteers. Healthy volunteers will be randomly (by chance) assigned to receive a single oral dose of canagliflozin followed by a single oral dose of placebo (inactive substance) or a single dose of placebo followed by a single dose of canagliflozin with a period of 7-10 days between treatments. Healthy volunteers will also receive intravenous (i.v.) infusion (injection in the vein) of somatostatin for 4 hours and a single dose i.v. injection of synthetic human C-peptide following administration of canagliflozin or placebo during each treatment period. Somatostatin will suppress the normal secretion of C-peptide, a protein that is released from the pancreas during insulin secretion, so that the human C-peptide administered to volunteers can be accurately measured. The total study duration for each volunteer will be approximately 44 days. During the study, blood and urine samples will be drawn (collected) for clinical laboratory evaluations.
Interventions
Singe over-encapsulated 300 mg tablet of canagliflozin administered orally (by mouth) on Day 1 of Treatment Period 1 or Day 1 of Treatment Period 2.
DRUGPlacebo
Singe capsule of placebo administered orally (by mouth) on Day 1 of Treatment Period 1 or Day 1 of Treatment Period 2.
DRUGSomatostatin
A primed (50 mcg in 1 mL sterile 0.9% NaCl solution i.v. injection over 1 minute) constant (500 mcg/hour) i.v. infusion of somatostatin for 4 hours approximately 2 hours after canagliflozin or placebo dosing on Day 1 of Treatment Period 1 and Day 1 of Treatment Period 2. The total dose of somatostatin administered during each period will be 50 mcg + 500 mcg/hour x 4 hours = 2050 mcg.
DRUGC-peptide
Single bolus dose of 150 mcg synthetic human C-peptide in 1 mL water for injection administered i.v. (in the vein) approximately 3 hours after canagliflozin or placebo dosing on Day 1 of Treatment Period 1 and Day 1 of Treatment Period 2.
Sponsors
Janssen-Cilag International NV
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers with a body mass index (BMI, a measure of a person's weight in relation to height) between 18 and 30 kg/m2, inclusive, and a body weight of not less than 50 kg
Exclusion criteria
* History of or current clinically significant medical illness as determined by the Investigator * History of clinically significant allergies, especially known hypersensitivity or intolerance to lactose * Known allergy or clinically significant adverse reactions to canagliflozin or placebo or any of the excipients of the canagliflozin or placebo formulation * Known hypersensitivity of synthetic human C-peptide, somatostatin preparation, or other structurally related peptides
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in C-peptide kinetic parameters | Before and after study drug administration on Day 1 of Treatment Periods 1 and 2 | Parameters are volume of distribution (Vd), clearance (CL) and half life (T1/2) |
Secondary
| Measure | Time frame |
|---|---|
| The number of volunteers who report adverse events | Up to 22 days following Day 1 of Treatment Period 1 |
Countries
Germany
Outcome results
None listed