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A Pharmacokinetic Study of the Relative Bioavailability of Paliperidone ER Formulations With Different Release Profiles and a Comparison to Paliperidone IR

Primary Purpose

Schizophrenia

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Paliperidone ER

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Paliperidone ER, Antipsychotic drugs, Schizophrenia, Mood disorders

Eligibility Criteria

18 Years - 55 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

Must agree to use an efficient method of birth control as deemed appropriate by the investigator and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
Body mass index (weight [kg]/height [m2]) between 18 and 30 kg/m2 (inclusive), and body weight not less than 50 kg
Blood pressure (after the volunteer is supine for 5 minutes) between 100 and 140 mmHg systolic, inclusive, and between 50 and 90 mmHg diastolic. Pulse rate measured over 60 seconds should be between 40 and 100 beats per minute (bpm)
Non-smoker

Exclusion Criteria:

History of or current significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the volunteer
History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including: bradycardia (heart rate < 40 bpm on the ECG), clinically significant abnormality on the ECG, demonstration of repeated prolonged QTcF > 450 ms (QTc interval corrected for heart rate using Fridericia's formula), as measured on more than one ECG (either during screening, or from prior medical record)
The following cardiac conditions: sick sinus syndrome, complete AV block, congestive heart failure, polymorphic ventricular tachycardia
Clinically relevant hypocalcemia, hypokalemia or hypomagnesemia
Presence of congenital prolongation of the QT interval (Romano-Ward Syndrome, Jervell and Lange-Nielsen syndrome)
History of any cancer, with the exception of basal cell carcinoma: Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at screening or at admission to the study center, in the opinion of the investigator
Clinically significant abnormality on physical examination, in the opinion of the investigator
At screening, has signs of orthostatic hypotension defined as a decrease in systolic ( > 20 mmHg) or diastolic (> 10 mmHg) blood pressure after standing for at least 2 minutes, that is associated with an increase in pulse rate of >15 bpm compared with supine measurements
Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for paracetamol (acetaminophen) or ibuprofen, within 14 days before the first dose of the study drug is scheduled

Sites / Locations

Outcomes

Primary Outcome Measures

To evaluate the pharmacokinetics and relative bioavailability of paliperidone ER formulations with different in vitro release rates (slow, fast) compared to the target formulation after a single 12 mg dose.

Secondary Outcome Measures

To evaluate the relative bioavailability of paliperidone ER formulations with different in vitro release rates compared to the paliperidone IR formulation, to explore an IVIVC for the paliperidone ER formulation, and to assess safey and tolerability

Full Information

NCT ID

NCT00791193

First Posted

November 13, 2008

Last Updated

May 17, 2011

Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

1. Study Identification

Unique Protocol Identification Number

NCT00791193

Brief Title

A Pharmacokinetic Study of the Relative Bioavailability of Paliperidone ER Formulations With Different Release Profiles and a Comparison to Paliperidone IR

Official Title

Pharmacokinetic Evaluation of the Relative Bioavailability of Three Paliperidone Extended Release (ER) Formulations With Different in Vitro Release Profiles, and Comparison to Paliperidone Immediate Release (IR), in Healthy Male Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

April 2010

Overall Recruitment Status

Completed

Study Start Date

March 2007 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

May 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

4. Oversight

5. Study Description

Brief Summary

The primary purpose of this study is to evaluate the pharmacokinetics and relative bioavailability of paliperidone ER formulations with slow, target, and fast in vitro release rates after administration of a single 12 mg dose. The slow and fast releasing ER tablets have in vitro release rates outside the current commercial specifications. Therefore, in order to support widening of the specification limits, this study will be performed. The target formulation to be used is representative of the commercial formulation. Other objectives of this study are 1) to compare the relative bioavailability of paliperidone ER formulations with slow, target, and fast in vitro release rates to the paliperidone IR formulation; 2) to explore the in vitro in vivo correlation (IVIVC) for the paliperidone ER formulation; and 3) to evaluate the safety and tolerability of the different paliperidone ER formulations.

Detailed Description

This is a randomized, open-label, 4-way crossover, single dose study in healthy male volunteers to evaluate the pharmacokinetic profiles of paliperidone ER tablets with slow, target, and fast in vitro release rates and paliperidone IR. The study consists of a 21 day screening phase, an open-label treatment phase consisting of 4 single-dose treatment periods (IR, slow, fast, and target formulations), and an end-of-study or early withdrawal phase. A 10- to 21 day washout period (i.e., >5 times the half-life) will separate each study drug administration (i.e., each open label treatment period). In the first period, all volunteers are given a 1-mg dose of paliperidone IR solution, administered as a single oral dose under fasted conditions (Treatment A). On Day 1 of Period 2, prior to study drug administration, all volunteers will be randomly assigned to 1 of 6 possible treatment sequences to ensure that they receive all of the following treatments, one in each period: 12-mg paliperidone ER tablet with a target in vitro release under fasted condition (Treatment B); 12-mg paliperidone ER tablet with a slow in vitro release under fasted condition (Treatment C); 12-mg paliperidone ER tablet with a fast in vitro release under fasted condition (Treatment D). In each treatment period, volunteers will enter the study center at least 10 hours before the study drug administration on Day 1 and will remain there until after collection of the 96 hour pharmacokinetic samples on Day 5 if the investigator considers that the volunteer is ready for discharge. It is expected that the differences in the in vitro release rate will not affect the relative bioavailability of paliperidone in vivo. Safety and tolerability of the different paliperidone ER formulations will be monitored throughout the study. Single oral doses of paliperidone ER 12 mg tablets with different release rates (target, fast, and slow); single oral dose of paliperidone IR 1 mg

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia

Keywords

Paliperidone ER, Antipsychotic drugs, Schizophrenia, Mood disorders

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

80 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Paliperidone ER

Primary Outcome Measure Information:

Title

Secondary Outcome Measure Information:

Title

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Must agree to use an efficient method of birth control as deemed appropriate by the investigator and to not donate sperm during the study and for 3 months after receiving the last dose of study drug Body mass index (weight [kg]/height [m2]) between 18 and 30 kg/m2 (inclusive), and body weight not less than 50 kg Blood pressure (after the volunteer is supine for 5 minutes) between 100 and 140 mmHg systolic, inclusive, and between 50 and 90 mmHg diastolic. Pulse rate measured over 60 seconds should be between 40 and 100 beats per minute (bpm) Non-smoker Exclusion Criteria: History of or current significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the volunteer History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including: bradycardia (heart rate < 40 bpm on the ECG), clinically significant abnormality on the ECG, demonstration of repeated prolonged QTcF > 450 ms (QTc interval corrected for heart rate using Fridericia's formula), as measured on more than one ECG (either during screening, or from prior medical record) The following cardiac conditions: sick sinus syndrome, complete AV block, congestive heart failure, polymorphic ventricular tachycardia Clinically relevant hypocalcemia, hypokalemia or hypomagnesemia Presence of congenital prolongation of the QT interval (Romano-Ward Syndrome, Jervell and Lange-Nielsen syndrome) History of any cancer, with the exception of basal cell carcinoma: Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at screening or at admission to the study center, in the opinion of the investigator Clinically significant abnormality on physical examination, in the opinion of the investigator At screening, has signs of orthostatic hypotension defined as a decrease in systolic ( > 20 mmHg) or diastolic (> 10 mmHg) blood pressure after standing for at least 2 minutes, that is associated with an increase in pulse rate of >15 bpm compared with supine measurements Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for paracetamol (acetaminophen) or ibuprofen, within 14 days before the first dose of the study drug is scheduled

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Clinical Trial

Organizational Affiliation

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Official's Role

Study Director

12. IPD Sharing Statement

Links:

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=761&filename=CR013474_CSR.pdf

Description

A pharmacokinetic study of the relative bioavailability of paliperidone ER formulations with different release profiles and a comparison to paliperidone IR

Learn more about this trial

A Pharmacokinetic Study of the Relative Bioavailability of Paliperidone ER Formulations With Different Release Profiles and a Comparison to Paliperidone IR

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