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

NCT ID: NCT01877889

Last Updated: 2014-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2014-03-31

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.

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part 1: Cana

Each volunteer will receive 300 mg of canagliflozin once daily for 4 days.

Group Type: EXPERIMENTAL

Canagliflozin

Intervention Type: DRUG

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 \[treatment period 1\]).

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).

Group Type: EXPERIMENTAL

Canagliflozin

Intervention Type: DRUG

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 \[treatment period 1\]).

Dapagliflozin

Intervention Type: DRUG

One 10 mg over-encapsulated tablet taken orally once daily for 4 days during Part 2 (Sequence 1 \[treatment period 1\] or Sequence 2 \[treatment period 2\]).

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.

Group Type: EXPERIMENTAL

Canagliflozin

Intervention Type: DRUG

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 \[treatment period 1\]).

Dapagliflozin

Intervention Type: DRUG

One 10 mg over-encapsulated tablet taken orally once daily for 4 days during Part 2 (Sequence 1 \[treatment period 1\] or Sequence 2 \[treatment period 2\]).

Interventions

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 \[treatment period 1\]).

Intervention Type: 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 \[treatment period 2\]).

Intervention Type: DRUG

Other Intervention Names

Invokana; Forxiga

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen-Cilag International NV

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen-Cilag International NV Clinical Trial

Role: STUDY_DIRECTOR

Janssen-Cilag International NV

Locations

Neuss, , Germany

Countries

Germany

Other Identifiers

28431754DIA1056

Identifier Type: OTHER

Identifier Source: secondary_id

2013-000994-54

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR101974

Identifier Type: -

Identifier Source: org_study_id