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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01559272
First received: March 13, 2012
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Schizophrenia
Drug: Paliperidone IR (Period 1)
Drug: Paliperidone palmitate F015 (Panel A: treatment group 1)
Drug: Paliperidone palmitate F015 (Panel A: treatment group 2)
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)
Drug: Paliperidone palmitate F016
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)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Plasma concentration of Paliperidone (Period 1) [ Time Frame: 14 time points over 96 hours ] [ Designated as safety issue: No ]
  • Plasma concentration of Paliperidone (Period 2) [ Time Frame: 29 time points over 544 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The change from baseline in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) (Period 1) [ Time Frame: Baseline and 96 hours ] [ Designated as safety issue: Yes ]
    The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.

  • Changes in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) observed across multiple time points between baseline and 544 days (Period 2) [ Time Frame: Baseline and 544 days ] [ Designated as safety issue: Yes ]
    The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.

  • The change from baseline in Clinical Global Impression (CGI-S) (Period 1) [ Time Frame: Baseline and 96 hours ] [ Designated as safety issue: Yes ]
    The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a subject. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill subjects". Higher scores indicate worsening.

  • Changes in Clinical Global Impression (CGI-S) observed across multiple time points between baseline and 544 days (Period 2) [ Time Frame: Baseline and 544 days ] [ Designated as safety issue: Yes ]
    The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a subject. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill subjects". Higher scores indicate worsening.

  • Changes from Baseline in Abnormal Involuntary Movement Scale (AIMS) for the ratings of dyskinesia (Period 1) [ Time Frame: Baseline and 96 hours ] [ Designated as safety issue: Yes ]
    The AIMS consists of 12 items to measure involuntary movements known as dyskinesia, with scores ranging from 0 (none) to 4 (severe).

  • Changes in Abnormal Involuntary Movement Scale (AIMS) for the ratings of dyskinesia observed across multiple time points between baseline and 544 days (Period 2) [ Time Frame: Baseline and 544 days ] [ Designated as safety issue: Yes ]
    The AIMS consists of 12 items to measure involuntary movements known as dyskinesia, with scores ranging from 0 (none) to 4 (severe).

  • Changes from Baseline in Barnes Akathisia Rating Scale (BARS) for the ratings of akathisia (Period 1) [ Time Frame: Baseline and 96 hours ] [ Designated as safety issue: Yes ]
    The BARS is a scale to assess the presence and severity of drug-induced akathisia (inner restlessness). It is scored as follows: Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness are rated on a 4-point scale from 0 (normal or absence of restlessness) to 3 (intense restlessness). The Global Clinical Assessment of Akathisia uses a 6-point scale ranging from 0 (absent) to 5 (severe akathisia).

  • Changes in Barnes Akathisia Rating Scale (BARS) for the ratings of akathisia observed across multiple time points between baseline and 544 days (Period 2) [ Time Frame: Baseline and 544 days ] [ Designated as safety issue: Yes ]
    The BARS is a scale to assess the presence and severity of drug-induced akathisia (inner restlessness). It is scored as follows: Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness are rated on a 4-point scale from 0 (normal or absence of restlessness) to 3 (intense restlessness). The Global Clinical Assessment of Akathisia uses a 6-point scale ranging from 0 (absent) to 5 (severe akathisia).

  • Changes from Baseline in Simpson and Angus Rating Scale (SAS) for the ratings of general extrapyramidal symptoms (EPS) (Period 1) [ Time Frame: Baseline and 96 hours ] [ Designated as safety issue: Yes ]
    The SAS is a 10-item instrument used to evaluate the presence and severity of extrapyramidal symptoms (EPS), such as akinesia (inability to initiate movement) and akathisia. Items are rated for severity on a 0 (normal) to 4 (severe symptoms) scale.

  • Changes in Simpson and Angus Rating Scale (SAS) for the ratings of general extrapyramidal symptoms (EPS) observed across multiple time points between baseline and 544 days (Period 2) [ Time Frame: Baseline and 544 days ] [ Designated as safety issue: Yes ]
    The SAS is a 10-item instrument used to evaluate the presence and severity of extrapyramidal symptoms (EPS), such as akinesia (inability to initiate movement) and akathisia. Items are rated for severity on a 0 (normal) to 4 (severe symptoms) scale.

  • Changes from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) (Period 1) [ Time Frame: Baseline and 96 hours ] [ Designated as safety issue: Yes ]
    The Columbia-Suicide Severity Rating Scale (C-SSRS) rates an individual's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent."

  • Changes in Columbia-Suicide Severity Rating Scale (C-SSRS) observed across multiple time points between baseline and 544 days (Period 2) [ Time Frame: Baseline and 544 days ] [ Designated as safety issue: Yes ]
    The Columbia-Suicide Severity Rating Scale (C-SSRS) rates an individual's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent."

  • Evaluation of the Injection Site (Period 1) [ Time Frame: 96 hours ] [ Designated as safety issue: Yes ]
    The investigator will evaluate the site of injection for redness, swelling, and induration. The evaluation will be assessed as 0 = absent, 1 = mild, 2 = moderate, 3 = severe.

  • Evaluation of the Injection Site (Period 2) [ Time Frame: Baseline through day 112 ] [ Designated as safety issue: Yes ]
    The investigator will evaluate the site of injection for redness, swelling, and induration. The evaluation will be assessed as 0 = absent, 1 = mild, 2 = moderate, 3 = severe.

  • Incidence of Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Approximately 84 weeks ] [ Designated as safety issue: Yes ]
  • Number of patients with abnormal clinical laboratory tests [ Time Frame: Approximately 84 weeks ] [ Designated as safety issue: Yes ]
  • Number of patients with abnormal findings in electrocardiogram, vital signs and physical examination [ Time Frame: Approximately 84 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 326
Study Start Date: February 2008
Study Completion Date: May 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panel A
Panel A consists of 2 treatment groups
Drug: 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.
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.
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.
Experimental: Panel B
Panel B consists of 5 treatment groups
Drug: 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.
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.
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.
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.
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.
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.
Experimental: Panel C
Panel C consists of 1 treatment group
Drug: 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.
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.
Experimental: Panel D
Panel D consists of 4 treatment groups
Drug: 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.
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.
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.
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.
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01559272

  Show 36 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01559272     History of Changes
Other Study ID Numbers: CR012652, R092670PSY1005, 2007-003581-17
Study First Received: March 13, 2012
Last Updated: June 23, 2014
Health Authority: Croatia: Ministry of Health and Social Care
Spain: Spanish Agency of Medicines
United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency

Keywords provided by Janssen Research & Development, LLC:
Schizophrenia
Paliperidone palmitate
R092670
Paliperidone
3-month formulation
Pharmacokinetics

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
9-hydroxy-risperidone
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on July 26, 2014