Effects of Canagliflozin on C-peptide Clearance in Healthy Volunteers

Sponsor

Janssen-Cilag International NV (Industry)

Overall Status

Completed

CT.gov ID

NCT01665638

Collaborator

(none)

Enrollment

Location

Arms

Duration (Days)

10.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Canagliflozin 300 mg Drug: Placebo Drug: Somatostatin Drug: C-peptide	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Official Title:

A Double-Blind, Randomized, Placebo-Controlled, 2-Way Cross-Over Study to Evaluate the Effect of Single Dose Canagliflozin on Kinetics of C-Peptide in Healthy Subjects

Study Start Date :

Sep 1, 2012

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Sequence Group AB	Drug: Canagliflozin 300 mg 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. Drug: Placebo Singe capsule of placebo administered orally (by mouth) on Day 1 of Treatment Period 1 or Day 1 of Treatment Period 2. Drug: Somatostatin 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. Drug: C-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.
Experimental: Treatment Sequence Group BA	Drug: Canagliflozin 300 mg 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. Drug: Placebo Singe capsule of placebo administered orally (by mouth) on Day 1 of Treatment Period 1 or Day 1 of Treatment Period 2. Drug: Somatostatin 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. Drug: C-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.

Arm

Intervention/Treatment

Experimental: Treatment Sequence Group AB

Drug: Canagliflozin 300 mg

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.

Drug: Placebo

Singe capsule of placebo administered orally (by mouth) on Day 1 of Treatment Period 1 or Day 1 of Treatment Period 2.

Drug: Somatostatin

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.

Drug: C-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.

Experimental: Treatment Sequence Group BA

Drug: Canagliflozin 300 mg

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.

Drug: Placebo

Singe capsule of placebo administered orally (by mouth) on Day 1 of Treatment Period 1 or Day 1 of Treatment Period 2.

Drug: Somatostatin

Drug: C-peptide

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

The number of volunteers who report adverse events [Up to 22 days following Day 1 of Treatment Period 1]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts 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