A Study of the Pharmacokinetics of Paliperidone in Volunteers With Normal or Impaired Liver Function
Information source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia; Hepatic Impairment
Intervention: Intermediate release (IR) Paliperidone (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Official(s) and/or principal investigator(s): Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Study Director, Affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Summary
The purpose of this study is 1) to investigate the single-dose pharmacokinetics of immediate
release (IR) paliperidone, after oral administration, in patients having moderate hepatic
impairment compared to patients having normal hepatic function, 2) to document the plasma
protein binding and disposition of the enantiomers of paliperidone, and 3) to evaluate the
tolerability and safety profile of IR paliperidone in both patient populations.
Clinical Details
Official title: Pharmacokinetics of Paliperidone in Subjects With Moderate Hepatic Impairment as Compared to Subjects With Normal Hepatic Function.
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To investigate the single-dose pharmacokinetics of IR paliperidone after oral administration to patients with moderate hepatic impairment as compared to patients with normal hepatic function
Secondary outcome: To document the plasma protein binding and disposition of the enantiomers of paliperidone and to evaluate the tolerability and safety profile of IR paliperidone in both patient populations
Detailed description:
This is a single-dose, parallel-group, open-label, single-center, Phase 1 study of immediate
release (IR) paliperidone in patients having either normal or moderately-impaired hepatic
function. The groups, which will consist of 10 patients each, will be demographically
matched with respect to age, weight, sex, and ethnicity. The study will consist of a
screening period of up to 3 weeks and an open-label, single-dose treatment period (Days 1
through 5). On Day 1, a single dose of 1 mg Intermediate Release (IR) paliperidone oral
solution will be administered after a fast of at least 10 hours; patients will continue to
fast for 4 hours following study drug administration. The 96-hour follow-up will consist of
serial sample collections of blood and urine for pharmacokinetic analysis and safety and
tolerability assessments. Patients will remain confined to the study site through the
72-hour pharmacokinetics sampling and will consume standard institutional meals while in the
study site. Patients will be released after the 72-hour sampling, then will return to the
study site on Day 5 before the 96-hour pharmacokinetics sampling; end-of-study procedures
will be performed immediately thereafter. Currently, pharmacokinetic data are available
after oral IR and Extended Release (ER) formulations of paliperidone were administered to
healthy patients and to patients with schizophrenia who had normal hepatic function. No
pharmacokinetic information on paliperidone in patients with hepatic impairment has been
obtained. The target population for paliperidone comprises schizophrenic patients. Because
some patients in the target population might be hepatically impaired, pharmacokinetic
information in this population is helpful. This single-dose pharmacokinetic study will
collect information in patients with normal hepatic function and in patients with moderate
hepatic impairment to provide clinical dosing information/recommendations for patients with
hepatic impairment. Safety and tolerability will be monitored. A single dose of 1 mg
intermediate release (IR) paliperidone oral solution
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients with normal hepatic function: Normotensive at screening, with supine (5
minutes) blood pressure between the range of 95 to 160 mmHg systolic, inclusive, and
55 to 95 mmHg diastolic, inclusive, demographically comparable to the hepatic
impairment group with respect to age, weight, sex, and ethnicity and healthy on the
basis of a prestudy physical examination, medical history, ECG, and laboratory
results of blood biochemistry, hematology, and urinalysis performed within 3 weeks
before study drug administration. If the results of the biochemistry or hematology
tests or the urinalysis are not within the laboratory's reference ranges, the patient
can be included only if the investigator judges that the deviations are not
clinically significant
- Patients with moderate hepatic impairment: Blood pressure controlled and stable on
antihypertensive agents, stable hepatic disease with laboratory and clinical findings
that support the diagnosis of hepatic impairment, otherwise healthy on the basis of a
prestudy physical examination, medical history, ECG, and laboratory results of blood
biochemistry, hematology, and urinalysis performed within 3 weeks before study drug
administration. Patients with controlled hypertension and those problems directly
associated with the primary diagnosis of hepatic impairment may be included. Patients
with stable, mild, chronic concurrent diseases, such as degenerative joint disease,
Type II diabetes, or thyroid conditions requiring thyroid replacement therapy or
surgery, may be included. If the results of the biochemistry or hematology tests or
the urinalysis are not within the laboratory's references ranges, the patient can be
included only if the investigator judges that the deviations are not clinically
significant. Laboratory results related to the patient's underlying condition may be
outside of the normal ranges. (Serum bilirubin, albumin, and prothrombin time will be
assessed individually)
- Total score of Child-Pugh's classification will be between 7 and 9, inclusive
- Concomitant medications to treat underlying disease states or medical conditions
related to hepatic insufficiency are allowed. Patients have to be on a stable dose of
medication and/or treatment regimen 2 months before the study, as well as during the
study.
Exclusion Criteria:
- Patients with normal hepatic function: Has any significant history or presence of
hepatic disease or has positive serology result for hepatitis B surface antigen
(HBsAg) or anti-hepatitis C virus (as determined by a multi-antigen enzyme
immunoassay)
- At screening, sustained drops in systolic (>20 mmHg) or diastolic (>10 mmHg) blood
pressure after standing for at least 2 minutes which are not associated with an
increase in pulse rate of >15 beats per minute
- Is taking, or has taken, any prescribed or over-the-counter drug (including vitamins
and herbal supplements) within 2 weeks before study drug administration (with the
exception of paracetamol, hormonal contraceptives, and hormone replacement therapy)
- Patients with moderate hepatic impairment: Has any clinically significant laboratory
abnormality except those parameters influenced by hepatic impairment, has a score of
3 or 4 for hepatic encephalopathy as determined by the result of the Number
Connection Test, has severe ascites and/or pleural effusion, has serology result
positive for HBsAg, has acute exacerbation of liver disease, as indicated by
worsening clinical signs of hepatic impairment, or by an increase of more than 50% in
total bilirubin or prothrombin time in the preceding 3 months (as far as information
is available).
Locations and Contacts
Additional Information
A study of the pharmacokinetics of paliperidone in volunteers with normal or impaired liver function
Starting date: August 2004
Last updated: June 6, 2011
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