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

NCT01559272 | Completed Phase 1

• 3 other identifiers: CR012652R092670PSY10052007-003581-17
• Study Type: interventional
• Target: 328
• Locations: 11 countries
• Sites: 36

Brief Summary

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

Conditions

Schizophrenia

Keywords

Schizophrenia; Paliperidone palmitate; R092670; Paliperidone; 3-month formulation; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Plasma concentration of Paliperidone (Period 1)

  14 time points over 96 hours

• Plasma concentration of Paliperidone (Period 2)

  29 time points over 544 days

Secondary Outcomes (17)

• The change from baseline in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) (Period 1)

  Baseline and 96 hours

• Changes in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) observed across multiple time points between baseline and 544 days (Period 2)

  Baseline and 544 days

• The change from baseline in Clinical Global Impression (CGI-S) (Period 1)

  Baseline and 96 hours

• Changes in Clinical Global Impression (CGI-S) observed across multiple time points between baseline and 544 days (Period 2)

  Baseline and 544 days

• Changes from Baseline in Abnormal Involuntary Movement Scale (AIMS) for the ratings of dyskinesia (Period 1)

  Baseline and 96 hours

Study Arms (4)

Panel A

EXPERIMENTAL

Panel A consists of 2 treatment groups

Drug: Paliperidone IR (Period 1); Drug: Paliperidone palmitate F015 (Panel A: treatment group 1); Drug: Paliperidone palmitate F015 (Panel A: treatment group 2)

Panel B

EXPERIMENTAL

Panel B consists of 5 treatment groups

Drug: Paliperidone IR (Period 1); Drug: Paliperidone palmitate F015 (Panel B: treatment group 1); Drug: Paliperidone palmitate F015 (Panel B: treatment group 2); Drug: Paliperidone palmitate F015 (Panel B: treatment group 3); Drug: Paliperidone palmitate F015 (Panel B: treatment group 4); Drug: Paliperidone palmitate F015 (Panel B: treatment group 5)

Panel C

EXPERIMENTAL

Panel C consists of 1 treatment group

Drug: Paliperidone IR (Period 1); Drug: Paliperidone palmitate F016

Panel D

EXPERIMENTAL

Panel D consists of 4 treatment groups

Drug: Paliperidone IR (Period 1); Drug: Paliperidone palmitate F015 (Panel D: treatment group 1); Drug: Paliperidone palmitate F015 (Panel D: treatment group 2); Drug: Paliperidone palmitate F015 (Panel D: treatment group 3); Drug: Paliperidone palmitate F015 (Panel D: treatment group 4)

Interventions

Paliperidone IR (Period 1) 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.

Panel A; Panel B; Panel C; Panel D

Paliperidone palmitate F015 (Panel A: treatment group 1) 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.

Panel A

Paliperidone palmitate F015 (Panel A: treatment group 2) 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 A

Paliperidone palmitate F015 (Panel B: treatment group 1) 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.

Panel B

Paliperidone palmitate F015 (Panel B: treatment group 2) 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.

Panel B

Paliperidone palmitate F015 (Panel B: treatment group 3) 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.

Panel B

Paliperidone palmitate F015 (Panel B: treatment group 4) 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.

Panel B

Paliperidone palmitate F015 (Panel B: treatment group 5) 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 B

Paliperidone palmitate F016 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 C

Paliperidone palmitate F015 (Panel D: treatment group 1) 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.

Panel D

Paliperidone palmitate F015 (Panel D: treatment group 2) 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.

Panel D

Paliperidone palmitate F015 (Panel D: treatment group 3) 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.

Panel D

Paliperidone palmitate F015 (Panel D: treatment group 4) 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.

Panel D

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (36)

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Little Rock, Arkansas, United States

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Cerritos, California, United States

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Garden Grove, California, United States

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Glendale, California, United States

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National City, California, United States

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Paramount, California, United States

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Atlanta, Georgia, United States

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Philadelphia, Pennsylvania, United States

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Austin, Texas, United States

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DeSoto, Texas, United States

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Aalst, Belgium

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Diest, Belgium

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Burgas, Bulgaria

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Zagreb, Croatia

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Beer Yaakov, Israel

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Hod HaSharon, Israel

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Ramat Gan, Israel

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Johor Bahru, Malaysia

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Kuala Lumpur, Malaysia

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Perak, Malaysia

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Bratislava, Slovakia

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Michalovce, Slovakia

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Rimavská Sobota, Slovakia

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Bloemfontein, South Africa

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Cape Town, South Africa

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Incheon, South Korea

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Jeonju, South Korea

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Seoul, South Korea

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Badajoz, Spain

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Badalona, Spain

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Barcelona, Spain

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Seville, Spain

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Zamora, Spain

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Hualien City, Taiwan

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Taipei, Taiwan

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Taoyuan District, Taiwan

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Related Publications (3)

• 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.

  PMID: 27743205 DERIVED

• 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.

  PMID: 27333588 DERIVED

• 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.

  PMID: 26306819 DERIVED

Related Links

• 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

MeSH Terms

Conditions

Schizophrenia

Interventions

Paliperidone Palmitate

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2012
• First Posted: March 21, 2012
• Study Start: February 21, 2008
• Primary Completion: April 9, 2014
• Study Completion: May 24, 2014
• Last Updated: September 18, 2017

Record last verified: 2017-09

Locations

IL (3); US (10); ZA (2); BE (2); MY (3); KR (3); BU (1); SL (3); CR (1); ES (5); TW (3)