A Study of Canagliflozin in Study Participants With Various Degrees of Impaired Hepatic (Liver) Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT01186588
First received: August 19, 2010
Last updated: May 27, 2013
Last verified: May 2013
  Purpose

The purpose of the study is to determine the concentration of canagliflozin in blood and urine samples after the administration of canagliflozin to study participants with mild or moderate hepatic (liver) impairment compared with study participants with normal hepatic function.


Condition Intervention Phase
Healthy
Hepatic Insufficiency
Drug: Canagliflozin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: An Open-Label Study to Evaluate the Pharmacokinetics of a Single Oral Dose of 300 mg JNJ-28431754 (Canagliflozin) in Subjects With Various Degrees of Impaired Hepatic Function Compared With Subjects With Normal Hepatic Function

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Plasma concentrations of canagliflozin to evaluate protocol-specified pharmacokinetic parameters [ Time Frame: At protocol-specified time points before and after dosing on Day 1 through Day 6 ] [ Designated as safety issue: No ]
  • Urine concentrations of canagliflozin to evaluate protocol-specified pharmacokinetic parameters [ Time Frame: At protocol-specified time points after dosing on Day 1 through Day 3 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma concentrations of canagliflozin metabolites, (M5 and M7 to evaluate protocol-specified pharmacokinetic parameters [ Time Frame: At protocol-specified time points before and after dosing on Day 1 through Day 6 ] [ Designated as safety issue: No ]
  • Urine concentrations of canagliflozin metabolites (M5 and M7) to evaluate protocol-specified pharmacokinetic parameters [ Time Frame: At protocol-specified time points after dosing on Day 1 through Day 3 ] [ Designated as safety issue: No ]
  • Adverse events reported [ Time Frame: From Screening (up to 23 days prior to dosing) to 7 to 10 days after Day 6 or at the time of early withdrawal from the study. ] [ Designated as safety issue: No ]
  • Vital signs measurements and results from electrocardiograms [ Time Frame: From Screening (up to 23 days prior to dosing) to 7 to 10 days after Day 6 or at the time of early withdrawal from the study. ] [ Designated as safety issue: No ]
  • Physical examination findings [ Time Frame: From Screening (up to 23 days prior to dosing) to 7 to 10 days after Day 6 or at the time of early withdrawal from the study. ] [ Designated as safety issue: No ]
  • Laboratory test results [ Time Frame: From Screening (up to 23 days prior to dosing) to 7 to 10 days after Day 6 or at the time of early withdrawal from the study. ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: August 2010
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
Canagliflozin One 300-mg dose of canagliflozin on Day 1
Drug: Canagliflozin
One 300-mg dose of canagliflozin on Day 1

Detailed Description:

This is an open-label (both study participant and investigator will know the name of the assigned treatment), pharmacokinetic (the study of how drugs are absorbed in the body, how they are distributed within the body, and how they are removed from the body over time) study of canagliflozin in adult study participants with mild or moderate hepatic (liver) impairment compared to study participants with normal hepatic function. Approximately 24 study participants who meet entry criteria for the study will be classified into 1 of 3 hepatic function groups: Group 1 (8 study participants with normal hepatic function), Group 2 (8 study participants with mild hepatic impairment) and Group 3 (8 study participants with moderate hepatic impairment). The group allocation is based on the Child-Pugh score, an assessment of 5 clinical measures that is used to characterize the degree of hepatic impairment. At least 3 men and 3 women will be enrolled in each group and the 3 groups will be balanced with respect to an average age and body weight. Study participants will be required to stay overnight at the study center for 5 nights to receive study drug and have study procedures and safety assessments performed. All study participants will be administered a single 300-mg oral (by mouth) dose of canagliflozin after fasting (not eating food) for a period of at least 10 hours. After study drug administration, study participants will be provided with standardized meals (breakfast, lunch, and dinner). Blood and urine samples for analyses of canagliflozin and metabolites (M7 and M5) will be collected from study participants at specified time points up to 120 hours (blood) and 48 hours (urine) after study drug administration. After discharge from the study center, study participants will be required to return to the study center for 3 outpatient visits to have study procedures and safety assessments performed. Study participants will be monitored for safety during the study by evaluating adverse events reported and results from clinical laboratory tests, 12-lead electrocardiograms (ECGs), vital sign measurements, and physical examinations. On Day 1 of the study, a single 300 mg dose of canagliflozin will be orally administered to study participants after a fasting period of at least 10 hours followed 10 minutes later by a standardized breakfast that must be eaten within 30 minutes. Study participants are to remain standing or sitting for the first 4 hours after dosing. At 2 hours after dosing (but not earlier) all study participants must drink 1 glass of water; drinking of water is allowed from then onwards.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • All study participants must have a body mass index (ie, a measure of one's weight in relation to height) between 18 and 33 kg/m2 (inclusive)
  • Study participants with normal hepatic function must have blood pressure at screening and before study drug administration between 90 and 160 mmHg systolic, inclusive, and 55 and 100 mmHg diastolic, inclusive
  • Study participants with normal hepatic function should be comparable to the groups with hepatic impairment with respect to mean (average) age (range of +/- 15 years) and mean weight (range of +/- 25%)
  • Study participants with mild or moderate hepatic impairment must be otherwise in acceptable clinical condition on the basis results from prestudy assessments, have a total Child-Pugh score of 5 or 6 (mild hepatic impairment) or a score of between 7 and 9, inclusive (moderate hepatic impairment)
  • In study participants with mild or moderate hepatic impairment, concomitant therapy to treat underlying disease states or medical conditions related to hepatic insufficiency are allowed

Exclusion Criteria:

  • Study participants with normal hepatic function who have a history of or current medical illness deemed clinically significant by the investigator, use of any prescription or nonprescription medication, except for acetaminophen, oral contraceptives and hormonal replacement therapy within 14 days before the study drug administration, and have a positive test for drugs of abuse before study drug administration
  • Study participants with mild or moderate hepatic impairment who have a positive test for drugs of abuse, have severe ascites or pleural effusion (accumulation of fluid in the abdomen and lungs, respectively), have a score of 3 or 4 for hepatic encephalopathy
  • have acute exacerbation (worsening) of liver disease, as indicated by worsening clinical signs of hepatic impairment, or by an increase in total bilirubin (a liver function test) or prothrombin time (ie, the time it takes blood to clot) of more than 50% in the 3 months prior to study entry
  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: NCT01186588

Locations
United States, Florida
Orlando, Florida, United States
United States, Tennessee
Knoxville, Tennessee, 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: NCT01186588     History of Changes
Other Study ID Numbers: CR017227
Study First Received: August 19, 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
JNJ-28431754
Liver diseases
Hepatic impairment
Pharmacokinetic
Normal hepatic function

Additional relevant MeSH terms:
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on July 29, 2014