Effects of Canagliflozin on C-peptide Clearance in Healthy Volunteers - Full Text View

Purpose

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	Intervention	Phase
Healthy	Drug: Canagliflozin 300 mg Drug: Placebo Drug: Somatostatin Drug: C-peptide	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Drug Information available for: Somatostatin Canagliflozin

U.S. FDA Resources

Further study details as provided by Janssen-Cilag International NV:

Primary Outcome Measures:

Change from baseline in C-peptide kinetic parameters [ Time Frame: Before and after study drug administration on Day 1 of Treatment Periods 1 and 2 ] [ Designated as safety issue: No ]
Parameters are volume of distribution (Vd), clearance (CL) and half life (T1/2)

Secondary Outcome Measures:

The number of volunteers who report adverse events [ Time Frame: Up to 22 days following Day 1 of Treatment Period 1 ] [ Designated as safety issue: No ]

Enrollment:	10
Study Start Date:	September 2012
Study Completion Date:	October 2012
Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

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.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01665638

Locations

Germany

Neuss, Germany

Sponsors and Collaborators

Janssen-Cilag International NV

Investigators

Study Director:

Janssen-Cilag International NV Clinical Trial

Janssen-Cilag International NV

More Information

No publications provided

Responsible Party:	Janssen-Cilag International NV
ClinicalTrials.gov Identifier:	NCT01665638 History of Changes
Other Study ID Numbers:	CR100800, 28431754DIA1049, 2012-001667-73
Study First Received:	August 13, 2012
Last Updated:	March 1, 2013
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices (BfArM) Germany: Ethics Commission

Keywords provided by Janssen-Cilag International NV:

Healthy
Clearance
Canagliflozin
JNJ-28431754

Placebo
Somatostatin
C-peptide

Additional relevant MeSH terms:

Somatostatin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013