A Study of Canagliflozin in Study Participants With Various Degrees of Impaired Hepatic (Liver) Function
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 001 Canagliflozin One 300-mg dose of canagliflozin on Day 1 |
Drug: Canagliflozin
One 300-mg dose of canagliflozin on Day 1
|
Outcome Measures
Primary Outcome Measures
- Plasma concentrations of canagliflozin to evaluate protocol-specified pharmacokinetic parameters [At protocol-specified time points before and after dosing on Day 1 through Day 6]
- Urine concentrations of canagliflozin to evaluate protocol-specified pharmacokinetic parameters [At protocol-specified time points after dosing on Day 1 through Day 3]
Secondary Outcome Measures
- Plasma concentrations of canagliflozin metabolites, (M5 and M7 to evaluate protocol-specified pharmacokinetic parameters [At protocol-specified time points before and after dosing on Day 1 through Day 6]
- Urine concentrations of canagliflozin metabolites (M5 and M7) to evaluate protocol-specified pharmacokinetic parameters [At protocol-specified time points after dosing on Day 1 through Day 3]
- Adverse events reported [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.]
- Vital signs measurements and results from electrocardiograms [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.]
- Physical examination findings [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.]
- Laboratory test results [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.]
Eligibility Criteria
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
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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%)
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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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Orlando | Florida | United States | ||
| 2 | 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.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- CR017227