A Pharmacokinetic and Pharmacodynamic Study to Determine Blood Levels of JNJ-28431754 (Canagliflozin) in Patients With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT01128985
First received: May 20, 2010
Last updated: May 27, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to evaluate the pharmacokinetics (blood levels of the drug) and pharmacodynamics (effects of the drug on the body) of canagliflozin after oral administration to patients with type 2 diabetes mellitus.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Canagliflozin 50 mg
Drug: Canagliflozin 100 mg
Drug: Canagliflozin 300 mg
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled, Randomized, Parallel-Group, Multi-Center Study to Evaluate the Multiple Dose Pharmacokinetic and Pharmacodynamic Characteristics of JNJ-28431754 (Canagliflozin) in Subjects With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • The concentration of canagliflozin and major metabolites (M5 and M7) in blood will be measured by protocol-specified pharmacokinetic parameters. [ Time Frame: At protocol-specified time points through Day 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The relationship between the concentration of glucose in patient blood measured by protocol-specified pharmacodynamic parameters [ Time Frame: At protocol-specified time points from baseline to Day 7 ] [ Designated as safety issue: No ]
  • The safety and tolerability of canagliflozin will be determined by monitoring adverse events and findings from laboratory evaluations, vital signs measurements, and ECG measurements reported. [ Time Frame: At protocol-specified time points from the time of screening (Day -44 to Day -23) to end-of-study (7 to 10 days after Day 7 or at the time of early withdrawal from the study) ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: March 2010
Study Completion Date: July 2010
Arms Assigned Interventions
Experimental: 001
Canagliflozin 50 mg 50 mg capsule once daily for 7 consecutive days from Day 1 to Day 7
Drug: Canagliflozin 50 mg
50 mg capsule once daily for 7 consecutive days from Day 1 to Day 7
Experimental: 002
Canagliflozin 100 mg 100 mg capsule once daily for 7 consecutive days from Day 1 to Day 7
Drug: Canagliflozin 100 mg
100 mg capsule once daily for 7 consecutive days from Day 1 to Day 7
Experimental: 003
Canagliflozin 300 mg 300 mg capsule once daily for 7 consecutive days from Day 1 to Day 7.
Drug: Canagliflozin 300 mg
300 mg capsule once daily for 7 consecutive days from Day 1 to Day 7.
Placebo Comparator: 004
Placebo matching canagliflozin placebo once daily for 7 consecutive days from Day 1 to Day 7
Drug: Placebo
matching canagliflozin placebo once daily for 7 consecutive days from Day 1 to Day 7

Detailed Description:

Canagliflozin is a drug that is being tested to see if it may be useful in treating patients diagnosed with type 2 diabetes mellitus (T2DM). This is a randomized (patients will assigned to 1 of 4 study treatments by chance), double-blind (neither the patient or the study doctor will know the name of the assigned treatment), study to assess the pharmacokinetics (blood levels) and pharmacodynamics (effects of the drug on the body) of canagliflozin compared to a placebo (a capsule that looks like all the other treatments but has no real medicine) in patients with T2DM. Approximately 36 patients with T2DM will receive once-daily treatment with canagliflozin (50 mg, 100 mg, or 300 mg doses) or placebo for 7 days. Patients will participate in the study for approximately 9 weeks. Blood and urine samples will be collected at specified times before and after each dose of study drug for pharmacokinetic and pharmacodynamic analyses. A blood sample will also be collected before the first dose of study drug for pharmacogenomic analysis (ie, genetic testing) for possible use in characterizing the safety and/or efficacy of study drug in relation to the patient pharmacogenic profile. During the study, the safety and tolerability of canagliflozin will be evaluated by monitoring adverse events and findings from laboratory evaluations, vital signs measurements, and ECG measurements. The primary outcome measure in the study is the concentration of canagliflozin and its major metabolites (M5 and M7) in the blood measured by protocol-specified pharmacokinetic parameters at protocol specified time points through Day 7. Study drug will be taken orally (by mouth) once daily before the first meal each day. On Day -1, patients will take 1 dose of placebo in single-blind fashion (patient blinded) to determine baseline assessments. After randomization, patients will take single doses of double-blind canagliflozin (50 mg, 100 mg, or 300 mg) or matching placebo once daily for 7 days (Day 1 through Day 7).

  Eligibility

Ages Eligible for Study:   25 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients must have a diagnosis of T2DM for at least 1 year, but not more than 12 years prior to Day -1 of the study and be medically stable on the basis of physical examination, medical history, laboratory safety test results, vital signs and electrocardiogram (ECG) performed at Screening
  • Patients must be on generally stable approved anti-hypeglycemic agent (AHA) regimen (i.e., with no change in medication, or only 1 dose step change in dose) for at least 2 months prior to the Screening Visit
  • Patients must have fasting plasma glucose (FPG) concentrations between 7.8 mM (140 mg/dL) and 15 mM (270 mg/dL) on Day -2

Exclusion Criteria:

  • History of clinically significant diabetic complications including retinopathy, nephropathy, or macro albuminuria, neuropathy, gastroparesis, or diabetic ketoacidosis
  • History of type 1 diabetes mellitus (T1DM)
  • History of repeated severe hypoglycemic episodes before screening
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01128985

Locations
United States, Florida
Fort Myers, Florida, United States
Miramar, Florida, United States
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT01128985     History of Changes
Other Study ID Numbers: CR017200, 28431754DIA1023
Study First Received: May 20, 2010
Last Updated: May 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Canagliflozin
Placebo
Type 2 diabetes mellitus
Pharmacokinetic
Pharmacodynamic

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on April 22, 2014