Effects of Canagliflozin on C-peptide Clearance in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV
ClinicalTrials.gov Identifier:
NCT01665638
First received: August 13, 2012
Last updated: June 6, 2013
Last verified: June 2013
  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:


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.

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: June 6, 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 September 18, 2014