Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

A Study to Compare the Pharmacodynamics of Canagliflozin and Dapagliflozin in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01877889
Recruitment Status : Completed
First Posted : June 14, 2013
Last Update Posted : March 26, 2014
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV

Brief Summary:
The purpose of this study is to compare the pharmacodynamics (ie, how the drug affects the body) of canagliflozin with the pharmacodynamics of dapagliflozin.

Condition or disease Intervention/treatment Phase
Healthy Drug: Canagliflozin Drug: Dapagliflozin Phase 1

Detailed Description:

The study will be conducted as a 2-part study. Part 1 is an open-label pilot study (the investigator and the participants know the identity of the assigned treatment) in which 6 healthy volunteers will be given 300 mg of canagliflozin once daily for 4 consecutive days. The total study duration for each volunteer in Part 1 will be approximately 35 days (including a screening phase, an open-label treatment phase, and a follow-up phase). Part 2 will be a double-blind (neither the investigator nor volunteers know the identity of the assigned treatment), randomized (the treatment is assigned by chance), 2-period crossover study (all volunteers will receive each of the 2 treatments but in a different order) with a two-stage sequential group design.

Approximately 34 healthy volunteers will be participating in the first stage. After all the participants of the first stage will complete Part 2, and the results are analyzed, based on the first stage outcomes the study will be either terminated or will proceed to the second stage, which will be conducted using the same study method as in the first stage.

Potentially, up to 30 volunteers will participate in the second stage. A total number of participants in Part 2 will be up to 64.

Volunteers assigned to Treatment Sequence 1 will receive 10 mg of dapagliflozin once daily for 4 consecutive days (Period 1), and after a 12- to 14-day washout period (with no medication), 300 mg of canagliflozin once daily for 4 days (Period 2). Volunteers assigned to Treatment Sequence 2 will receive 300 mg of canagliflozin once daily for 4 days (Period 1), and after a 12- to 14-day washout period, 10 mg of dapagliflozin once daily for 4 consecutive days (Period 2). The total study duration for each volunteer in Part 2 will be up to approximately 65 days (including a screening phase, a baseline phase, a double-blind treatment phase, a washout period, and a follow-up phase).

Volunteers can participate in Part 1 or Part 2 of the study, but not in both parts. Canagliflozin and dapagliflozin are used for the treatment of type 2 diabetes mellitus.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, 2-Way Crossover Study to Compare the Pharmacodynamics of Canagliflozin 300 mg Versus Dapagliflozin 10 mg in Healthy Subjects
Study Start Date : July 2013
Actual Primary Completion Date : March 2014
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1: Cana
Each volunteer will receive 300 mg of canagliflozin once daily for 4 days.
Drug: Canagliflozin
One 300 mg over-encapsulated tablet taken orally (by mouth) once daily for 4 days during Part 1 and Part 2 (Sequence 1 [treatment period 2] or Sequence 2 [treatment period 1]).
Other Name: Invokana

Experimental: Part 2: Sequence 1 (Dapa/Cana)
Each volunteer will receive 10 mg of dapagliflozin once daily for 4 days (treatment period 1) followed by 300 mg of canagliflozin once daily for 4 days (treatment period 2). Each treatment period will be separated by a 12- to 14-day washout period (with no medication).
Drug: Canagliflozin
One 300 mg over-encapsulated tablet taken orally (by mouth) once daily for 4 days during Part 1 and Part 2 (Sequence 1 [treatment period 2] or Sequence 2 [treatment period 1]).
Other Name: Invokana

Drug: Dapagliflozin
One 10 mg over-encapsulated tablet taken orally once daily for 4 days during Part 2 (Sequence 1 [treatment period 1] or Sequence 2 [treatment period 2]).
Other Name: Forxiga

Experimental: Part 2: Sequence 2 (Cana/Dapa)
Each volunteer will receive 300 mg of canagliflozin once daily for 4 days (treatment period 1) followed by 10 mg of dapagliflozin once daily for 4 days (treatment period 2). Each treatment period will be separated by a 12- to 14-day washout period.
Drug: Canagliflozin
One 300 mg over-encapsulated tablet taken orally (by mouth) once daily for 4 days during Part 1 and Part 2 (Sequence 1 [treatment period 2] or Sequence 2 [treatment period 1]).
Other Name: Invokana

Drug: Dapagliflozin
One 10 mg over-encapsulated tablet taken orally once daily for 4 days during Part 2 (Sequence 1 [treatment period 1] or Sequence 2 [treatment period 2]).
Other Name: Forxiga




Primary Outcome Measures :
  1. Between treatment difference in 24-hour mean renal threshold for glucose for canagliflozin (300 mg once daily for 4 days) compared to dapagliflozin (10 mg once daily for 4 days) [ Time Frame: Day 4 ]
    Renal threshold is defined as the plasma glucose concentration above which glucose is excreted in the urine.


Secondary Outcome Measures :
  1. Percent change from baseline in postprandial glucose area under the curve at 0-2 hours post-dose on Day 4 following 300 mg of canagliflozin once daily for 4 days or 10 mg of dapagliflozin once daily for 4 days [ Time Frame: Day -10 (Baseline) and Day 4 ]
    Area under the concentration time curve (or area under the curve) is a measure of the body's exposure to glucose over a specific time period.

  2. Number of volunteers with adverse events [ Time Frame: Up to Day 65 ]
    Adverse events will be used as a measure of safety and tolerability



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Volunteers must have a body mass index (BMI = weight in kg/height in m2) between 20 and 27 kg/m2 (inclusive), and body weight >= 50 kg at Screening
  • Volunteers must have a systolic blood pressure between 90 and 140 mmHg, inclusive, and a diastolic blood pressure no higher than 90 mmHg (based upon an average of 3 blood pressure readings at Screening)
  • Volunteers must be non-smokers

Exclusion Criteria:

  • Major surgery (eg, requiring general anesthesia) within 12 weeks before Screening, or planned during participation in the study, or within 2 weeks after the last dose of study drug administration, or volunteer will not have fully recovered from surgery during participation in the study; volunteers with planned surgical procedures to be conducted under local anesthesia may participate
  • History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening
  • History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
  • 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 volunteer from the study or that could interfere with the interpretation of the study results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01877889


Locations
Layout table for location information
Germany
Neuss, Germany
Sponsors and Collaborators
Janssen-Cilag International NV
Investigators
Layout table for investigator information
Study Director: Janssen-Cilag International NV Clinical Trial Janssen-Cilag International NV

Layout table for additonal information
Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT01877889    
Other Study ID Numbers: CR101974
28431754DIA1056 ( Other Identifier: Janssen-Cilag International NV )
2013-000994-54 ( EudraCT Number )
First Posted: June 14, 2013    Key Record Dates
Last Update Posted: March 26, 2014
Last Verified: March 2014
Keywords provided by Janssen-Cilag International NV:
Healthy
Canagliflozin
INVOKANA
Dapagliflozin
FORXIGA
Pharmacodynamics
Additional relevant MeSH terms:
Layout table for MeSH terms
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Canagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs