A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Paliperidone Palmitate in Patients With Schizophrenia

NCT ID: NCT01559272

Last Updated: 2017-09-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

328 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-02-21

Study Completion Date

2014-05-24

Brief Summary

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The purpose of this study is to assess the pharmacokinetics, safety, and tolerability of a paliperidone palmitate 3-month formulation in patients with schizophrenia.

Detailed Description

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This is a multicenter, randomized (the study drug is assigned by chance), open-label (all people know the identity of the intervention), parallel-group (each group of patients will be initiated simultaneously) study in 4 panels (A, B, C and D). Each panel will comprise 2 single-dose treatment periods. In Period 1, all patients from the 4 panels will receive an intramuscular (i.m.) injection with 1 mg paliperidone as an immediate release (IR) solution to assess tolerability and allergic or hypersensitivity reactions potentially related to paliperidone, and to establish the relative bioavailability (the extent to which a drug or other substance becomes available to the body) of paliperidone palmitate versus paliperidone IR. Patients in Panels A and C will receive an i.m. injection with 1 mg paliperidone IR solution in the gluteal muscle, and patients in Panel B and D will receive an i.m. injection with 1 mg paliperidone IR solution in the deltoid or gluteal muscle. Patients who tolerate this injection and have completed all assessments on Day 5 of Period 1 will be enrolled in Period 2. In Period 2, patients will receive a single dose of 3-month paliperidone palmitate i.m. injection at the dosages defined for each panel. The study drug injection will be followed by a 96-hour observation period in Period 1, and a 364-day or 544-day observation period in Period 2. Successive study drug administrations will be separated by a washout period (period when receiving no treatment) of at least 7 and no more than 21 days. The total study length for all patients is from 53 weeks to a maximum of 58 weeks. Patients in Panel B, if consented, and Panel D will participate in the extension period of approximately 26 weeks in order to obtain additional assessments to be able to characterize the pharmacokinetics (PK) profile. Pharmacokinetics explores how the drug is absorbed in the body, distributed within the body, and how it is removed from the body over time. Therefore, for those who participate in the extension period, the total study duration will be approximately 84 weeks.

Conditions

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Schizophrenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Panel A

Panel A consists of 2 treatment groups

Group Type EXPERIMENTAL

Paliperidone IR (Period 1)

Intervention Type DRUG

Type= exact number, unit= mg, number=1, form= injection, route= intramuscular use. Single injection with 1 mg paliperidone IR in the gluteal or deltoid muscle.

Paliperidone palmitate F015 (Panel A: treatment group 1)

Intervention Type DRUG

Type= exact number, unit= mg, number=300, form= injection, route= intramuscular use. Single injection with 300 mg eq. 3-month formulation paliperidone palmitate F015 manufactured by milling technique A, in the gluteal muscle.

Paliperidone palmitate F015 (Panel A: treatment group 2)

Intervention Type DRUG

Type= exact number, unit= mg, number=300, form= injection, route= intramuscular use. Single injection with 300 mg eq. 3-month formulation paliperidone palmitate F015 manufactured by milling technique B, in the gluteal muscle.

Panel B

Panel B consists of 5 treatment groups

Group Type EXPERIMENTAL

Paliperidone IR (Period 1)

Intervention Type DRUG

Type= exact number, unit= mg, number=1, form= injection, route= intramuscular use. Single injection with 1 mg paliperidone IR in the gluteal or deltoid muscle.

Paliperidone palmitate F015 (Panel B: treatment group 1)

Intervention Type DRUG

Type= exact number, unit= mg, number= 75, form= injection, route= intramuscular use. Single injection with 75 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.

Paliperidone palmitate F015 (Panel B: treatment group 2)

Intervention Type DRUG

Type= exact number, unit= mg, number=150, form= injection, route= intramuscular use. Single injection with 150 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.

Paliperidone palmitate F015 (Panel B: treatment group 3)

Intervention Type DRUG

Type= exact number, unit= mg, number=450, form= injection, route= intramuscular use. Single injection with 450 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.

Paliperidone palmitate F015 (Panel B: treatment group 4)

Intervention Type DRUG

Type= exact number, unit= mg, number=300, form= injection, route= intramuscular use. Single injection with 300 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.

Paliperidone palmitate F015 (Panel B: treatment group 5)

Intervention Type DRUG

Type= exact number, unit= mg, number=450, form= injection, route= intramuscular use. Single injection with 450 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.

Panel C

Panel C consists of 1 treatment group

Group Type EXPERIMENTAL

Paliperidone IR (Period 1)

Intervention Type DRUG

Type= exact number, unit= mg, number=1, form= injection, route= intramuscular use. Single injection with 1 mg paliperidone IR in the gluteal or deltoid muscle.

Paliperidone palmitate F016

Intervention Type DRUG

Type= exact number, unit= mg, number=150, form= injection, route= intramuscular use. Single injection with 150 mg eq. 3-month formulation paliperidone palmitate F016 in the gluteal muscle.

Panel D

Panel D consists of 4 treatment groups

Group Type EXPERIMENTAL

Paliperidone IR (Period 1)

Intervention Type DRUG

Type= exact number, unit= mg, number=1, form= injection, route= intramuscular use. Single injection with 1 mg paliperidone IR in the gluteal or deltoid muscle.

Paliperidone palmitate F015 (Panel D: treatment group 1)

Intervention Type DRUG

Type= exact number, unit= mg, number=525, form= injection, route= intramuscular use. Single injection with 525 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.

Paliperidone palmitate F015 (Panel D: treatment group 2)

Intervention Type DRUG

Type= exact number, unit= mg, number=525, form= injection, route= intramuscular use. Single injection with 525 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.

Paliperidone palmitate F015 (Panel D: treatment group 3)

Intervention Type DRUG

Type= exact number, unit= mg, number=350, form= injection, route= intramuscular use. Single injection with 350 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.

Paliperidone palmitate F015 (Panel D: treatment group 4)

Intervention Type DRUG

Type= exact number, unit= mg, number=175, form= injection, route= intramuscular use. Single injection with 175 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.

Interventions

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Paliperidone IR (Period 1)

Type= exact number, unit= mg, number=1, form= injection, route= intramuscular use. Single injection with 1 mg paliperidone IR in the gluteal or deltoid muscle.

Intervention Type DRUG

Paliperidone palmitate F015 (Panel A: treatment group 1)

Type= exact number, unit= mg, number=300, form= injection, route= intramuscular use. Single injection with 300 mg eq. 3-month formulation paliperidone palmitate F015 manufactured by milling technique A, in the gluteal muscle.

Intervention Type DRUG

Paliperidone palmitate F015 (Panel A: treatment group 2)

Type= exact number, unit= mg, number=300, form= injection, route= intramuscular use. Single injection with 300 mg eq. 3-month formulation paliperidone palmitate F015 manufactured by milling technique B, in the gluteal muscle.

Intervention Type DRUG

Paliperidone palmitate F015 (Panel B: treatment group 1)

Type= exact number, unit= mg, number= 75, form= injection, route= intramuscular use. Single injection with 75 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.

Intervention Type DRUG

Paliperidone palmitate F015 (Panel B: treatment group 2)

Type= exact number, unit= mg, number=150, form= injection, route= intramuscular use. Single injection with 150 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.

Intervention Type DRUG

Paliperidone palmitate F015 (Panel B: treatment group 3)

Type= exact number, unit= mg, number=450, form= injection, route= intramuscular use. Single injection with 450 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.

Intervention Type DRUG

Paliperidone palmitate F015 (Panel B: treatment group 4)

Type= exact number, unit= mg, number=300, form= injection, route= intramuscular use. Single injection with 300 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.

Intervention Type DRUG

Paliperidone palmitate F015 (Panel B: treatment group 5)

Type= exact number, unit= mg, number=450, form= injection, route= intramuscular use. Single injection with 450 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.

Intervention Type DRUG

Paliperidone palmitate F016

Type= exact number, unit= mg, number=150, form= injection, route= intramuscular use. Single injection with 150 mg eq. 3-month formulation paliperidone palmitate F016 in the gluteal muscle.

Intervention Type DRUG

Paliperidone palmitate F015 (Panel D: treatment group 1)

Type= exact number, unit= mg, number=525, form= injection, route= intramuscular use. Single injection with 525 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.

Intervention Type DRUG

Paliperidone palmitate F015 (Panel D: treatment group 2)

Type= exact number, unit= mg, number=525, form= injection, route= intramuscular use. Single injection with 525 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.

Intervention Type DRUG

Paliperidone palmitate F015 (Panel D: treatment group 3)

Type= exact number, unit= mg, number=350, form= injection, route= intramuscular use. Single injection with 350 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.

Intervention Type DRUG

Paliperidone palmitate F015 (Panel D: treatment group 4)

Type= exact number, unit= mg, number=175, form= injection, route= intramuscular use. Single injection with 175 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients diagnosed with schizophrenia or schizoaffective disorder, for at least 1 year before screening
* Clinically stable with no hospitalizations for schizophrenia exacerbation or change in current antipsychotic medications for 3 months prior to screening
* Stabilized on antipsychotic medications other than risperidone, paliperidone, ziprasidone, clozapine, thioridazine, or any long acting injectable.
* For panel D only, no detectable plasma concentration of risperidone or paliperidone \> 0.1ng/mL at screening. A quantifiable and stable level of paliperidone not exceeding 0.25 ng/mL is allowed if such paliperidone value is explained by (documented) use of paliperidone palmitate (last dose administered \> 12 months prior to baseline)
* Has a total PANSS score of 70 or less at both screening and Day-1 (Period 1)
* Woman is postmenopausal, surgically sterile, abstinent or, if sexually active, practices an effective method of birth control during participation in the study or for at least 6 months after the last dose of study drug, whichever is longer
* Woman has negative pregnancy test at screening and on Day -1 of Period 1
* Man agrees to use an adequate contraception method as deemed appropriate by the investigator and agrees to not donate sperm during participation in the study or for at least 6 months after the last dose of study drug, whichever is longer
* Body Mass Index (BMI) between 17 and 35 kg/m2 (inclusive). Body weight of at least 50 kg for patients enrolled in panel A, B and C. For patients enrolled in panel D only: body weight of at least 47 kg

Exclusion Criteria

* Attempted suicide within 12 months before screening or is at imminent risk of suicide or violent behavior
* Has diagnosis of alcohol or substance dependence, with the exception of nicotine or caffeine dependence, within 12 months prior to screening, or diagnosis of substance abuse within 3 months prior to screening
* Has a positive drug screen test for barbiturates, cocaine, amphetamines or opiates, or has a positive alcohol screen test unless positive toxicology screen is explained by a prescribed allowed medication
* Is in his/her first episode of psychosis
* Has a history of or has a current clinically significant medical illness that the investigator considers should exclude the patients or that could interfere with the interpretation of the study results
* Has clinically significant abnormal values at screening or at baseline for hematology, clinical chemistry or for urinalysis, as deemed appropriate by the investigator
* Has a clinically relevant abnormality in the physical examination, vital signs or 12 lead electrocardiogram (ECG) at screening or at baseline as deemed appropriate by the investigator
* Has a 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
* Concomitant use of medications that the investigator considers should exclude the patients or that could interfere with the interpretation of the study results
* Any other condition or circumstance that the investigator considers should exclude the patients or that could interfere with the interpretation of the study results
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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Little Rock, Arkansas, United States

Site Status

Cerritos, California, United States

Site Status

Garden Grove, California, United States

Site Status

Glendale, California, United States

Site Status

National City, California, United States

Site Status

Paramount, California, United States

Site Status

Atlanta, Georgia, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Austin, Texas, United States

Site Status

DeSoto, Texas, United States

Site Status

Aalst, , Belgium

Site Status

Diest, , Belgium

Site Status

Burgas, , Bulgaria

Site Status

Zagreb, , Croatia

Site Status

Beer Yaakov, , Israel

Site Status

Hod HaSharon, , Israel

Site Status

Ramat Gan, , Israel

Site Status

Johor Bahru, , Malaysia

Site Status

Kuala Lumpur, , Malaysia

Site Status

Perak, , Malaysia

Site Status

Bratislava, , Slovakia

Site Status

Michalovce, , Slovakia

Site Status

Rimavská Sobota, , Slovakia

Site Status

Bloemfontein, , South Africa

Site Status

Cape Town, , South Africa

Site Status

Incheon, , South Korea

Site Status

Jeonju, , South Korea

Site Status

Seoul, , South Korea

Site Status

Badajoz, , Spain

Site Status

Badalona, , Spain

Site Status

Barcelona, , Spain

Site Status

Seville, , Spain

Site Status

Zamora, , Spain

Site Status

Hualien City, , Taiwan

Site Status

Taipei, , Taiwan

Site Status

Taoyuan District, , Taiwan

Site Status

Countries

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United States Belgium Bulgaria Croatia Israel Malaysia Slovakia South Africa South Korea Spain Taiwan

References

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Magnusson MO, Samtani MN, Plan EL, Jonsson EN, Rossenu S, Vermeulen A, Russu A. Population Pharmacokinetics of a Novel Once-Every 3 Months Intramuscular Formulation of Paliperidone Palmitate in Patients with Schizophrenia. Clin Pharmacokinet. 2017 Apr;56(4):421-433. doi: 10.1007/s40262-016-0459-3.

Reference Type DERIVED
PMID: 27743205 (View on PubMed)

Samtani MN, Nandy P, Ravenstijn P, Remmerie B, Vermeulen A, Russu A, D'hoore P, Baum EZ, Savitz A, Gopal S, Hough D. Prospective dose selection and acceleration of paliperidone palmitate 3-month formulation development using a pharmacometric bridging strategy. Br J Clin Pharmacol. 2016 Nov;82(5):1364-1370. doi: 10.1111/bcp.13050. Epub 2016 Jul 24.

Reference Type DERIVED
PMID: 27333588 (View on PubMed)

Gopal S, Vermeulen A, Nandy P, Ravenstijn P, Nuamah I, Buron Vidal JA, Berwaerts J, Savitz A, Hough D, Samtani MN. Practical guidance for dosing and switching from paliperidone palmitate 1 monthly to 3 monthly formulation in schizophrenia. Curr Med Res Opin. 2015 Nov;31(11):2043-54. doi: 10.1185/03007995.2015.1085849. Epub 2015 Oct 2.

Reference Type DERIVED
PMID: 26306819 (View on PubMed)

Related Links

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http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_7051&studyid=1916&filename=CR012652_CSR.pdf

A Single-Dose, Open-Label, Randomized, Parallel-Group Study to Assess the Pharmacokinetics, Safety, and Tolerability of a Paliperidone Palmitate 3-Month Formulation in Subjects With Schizophrenia

Other Identifiers

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R092670PSY1005

Identifier Type: OTHER

Identifier Source: secondary_id

2007-003581-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR012652

Identifier Type: -

Identifier Source: org_study_id