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A Study of Paliperidone Palmitate 6-Month Formulation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03345342
Recruitment Status : Active, not recruiting
First Posted : November 17, 2017
Last Update Posted : October 18, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to demonstrate that injection cycles consisting of a single administration of paliperidone palmitate 6-month (PP6M) are not less effective than 2 sequentially administered injections of paliperidone palmitate 3-month PP3M) (350 or 525 mg eq.) for the prevention of relapse in participants with schizophrenia previously stabilized on corresponding doses of paliperidone palmitate 1-month (PP1M) (100 or 150 mg eq.) or PP3M (350 or 525 mg eq.).

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: PP6M Drug: PP3M 350 mg eq. Drug: PP3M 525 mg eq. Drug: PP1M Other: Placebo Phase 3

Detailed Description:
The primary hypothesis of this study is that the efficacy of PP6M is non-inferior to PP3M for preventing relapse in participants with schizophrenia who were previously stabilized on corresponding doses of PP1M or PP3M. The study consists of mainly 3 phases: a screening phase (up to 28 days), a maintenance phase (of 1 or 3 months), and a double-blind phase (of 12 months [neither the researchers nor the participants know what treatment the participant is receiving]). Additional/conditional phases include a transition phase (before maintenance phase). Study evaluations include efficacy, pharmacokinetics, pharmacodynamics, and safety. The study duration will vary from approximately 13 months to 19 months.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 841 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Active-controlled, Parallel-group Study of Paliperidone Palmitate 6-Month Formulation
Actual Study Start Date : November 20, 2017
Estimated Primary Completion Date : July 6, 2020
Estimated Study Completion Date : August 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: PP1M: Transition Phase
Participants who previously have not achieved stability with moderate to higher doses of Paliperidone palmitate 1-month (PP1M) or Paliperidone palmitate 3-month (PP3M) will enter into a transition period of up to 4 months. During transition period participants will receive 1 to 5 injections of PP1M 50 to 100 milligrams equivalent (mg eq.). The participants who achieved stability (stability is defined as at least 3 months of injections with the last 2 doses being the same strength) with PP1M 100 mg eq. will precede from transition phase to maintenance phase.
Drug: PP1M
Participants will receive intramuscular injection of PP1M 50 to 150 mg eq.
Other Name: R092670

Experimental: PP1M/PP3M: Maintenance Phase
All the participants will receive only 1 dose of PP1M 100 or 150 mg eq. or PP3M 350 or 525 mg eq. The participants will precede from maintenance phase to double-blind phase.
Drug: PP3M 350 mg eq.
Participants will receive intramuscular injection of PP3M 350 mg eq.
Other Name: R092670

Drug: PP3M 525 mg eq.
Participants will receive intramuscular injection of PP3M 525 mg eq.
Other Name: R092670

Drug: PP1M
Participants will receive intramuscular injection of PP1M 50 to 150 mg eq.
Other Name: R092670

Experimental: PP6M or Placebo: Double-Blind Phase
Participants will receive intramuscular injection of PP6M in left gluteal muscle on Day 1 and right gluteal muscle on Day 183 with alternating placebo in right gluteal muscle on Day 92 and left gluteal muscle on Day 274.
Drug: PP6M
Participants will receive intramuscular injection of PP6M.
Other Name: R092670

Other: Placebo
Participants will receive matching placebo.

Experimental: PP3M: Double-Blind Phase
Participants will receive intramuscular injections of PP3M at dose of 350 mg eq. or 525 mg eq. in left gluteal muscle on Day 1 and 274 and right gluteal muscle on Day 92 and 183.
Drug: PP3M 350 mg eq.
Participants will receive intramuscular injection of PP3M 350 mg eq.
Other Name: R092670

Drug: PP3M 525 mg eq.
Participants will receive intramuscular injection of PP3M 525 mg eq.
Other Name: R092670




Primary Outcome Measures :
  1. Time to Relapse During the Double-Blind (DB) Phase [ Time Frame: Up to Month 12 ]
    Time to relapse:Time between participant randomization in DB Phase and first documentation of a relapse event by the end of Month 12 of the DB phase. Relapse:Psychiatric hospitalization;participant had an increase of 25 % in total PANSS score from randomization for 2 consecutive assessments (CA) separated by 3-7 days if score at randomization was >40;had 10 point increase in total PANSS score from randomization for 2 CA separated by 3-7 days if score at randomization was <=40;deliberate self-injury or exhibited violent behavior results in suicide, clinically significant injury;suicidal/homicidal ideation and aggressive behavior;for PANSS items had score of greater than or equal to (>=) 5 after randomization for 2 CA separated by 3-7 days on any of above items if maximum score for these above PANSS items was <=3 at randomization;had score of >=6 after randomization for 2 CA separated by 3-7 days on any of above items if maximum score for these above PANSS items was 4 at randomization.


Secondary Outcome Measures :
  1. Change From Baseline in PANSS Total and Subscale Score at Month 3, 6, 9, 12 [ Time Frame: Baseline, Month 3, 6, 9, 12 ]
    The neuropsychiatric symptoms of schizophrenia will be assessed by using the 30-item Positive and Negative Syndrome Scale (PANSS). The PANSS provides a total score (sum of the scores of all 30 items) ranging from 30 to 210, higher scores indicate more severe neuropsychiatric symptoms of schizophrenia. Scores for 3 subscales, that is, for positive subscale (sum of the scores of all 7 items) and negative subscale (sum of the scores of all 7 items) ranges from 7 (absent) to 49 (extreme psychopathology), and for the general psychopathology subscale (sum of the scores of all 16 items) score ranges from 16 (absent) to 112 (extreme psychopathology).

  2. Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Score at Month 3, 6, 9, 12 [ Time Frame: Baseline, Month 3, 6, 9, 12 ]
    The Clinical Global Impression Severity (CGI-S) rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. 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 participants". Higher scores indicate worsening.

  3. Change From Baseline in Personal and Social Performance (PSP) Total Score at Month 3, 6, 9, 12 [ Time Frame: Baseline, Month 3, 6, 9, 12 ]
    The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The results of the assessment are converted to a numerical score from 1 to 100 points, which can be interpreted in 10-point intervals as excellent functioning (91 to 100 points), good functioning (81 to 90 points), mild difficulties (71 to 80 points), etc, as shown in the Manual of Assessments. Scores from 31 to 70 points indicate varying degrees of difficulty, and scores below 30 points indicate functioning so poor that intensive support or supervision is needed.

  4. Percentage of Participants who Met the Criteria for Symptomatic Remission [ Time Frame: Up to 19 months ]
    Symptomatic remission is defined as having a simultaneous score of mild or less (less than or equal to [<=3] points) on the following 8 items from the PANSS: the positive-symptom items P1 (delusions), P2 (conceptual disorganization), P3 (hallucinatory behavior); the negative-symptom items N1 (blunted affect), N4 (social withdrawal), and N6 (lack of spontaneity); and the general psychopathology items G5 (mannerisms/posturing) and G9 (unusual thought content).

  5. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to 90 days (Maintenance Phase); up to 365 days (Double-blind Phase) ]
    The Cmax is the maximum observed plasma concentration.

  6. Minimum Observed Plasma Concentration (Cmin) [ Time Frame: Up to 90 days (Maintenance Phase); up to 365 days (Double-blind Phase) ]
    The Cmin is the minimum observed plasma concentration.

  7. Treatment Satisfaction Questionnaire for Medication (TSQM-9) Score [ Time Frame: Up to 19 months ]
    TSQM-9 is a 9-item generic participant-reported outcome instrument to assess participant's satisfaction with medication and covers domains of effectiveness, convenience and global satisfaction. The instrument is scored by domain with scores ranging from 0-100 where a lower score indicates lower satisfaction.

  8. Satisfaction with Participation in Social Roles (SPSR) [ Time Frame: Up to 19 months ]
    The SPSR Short Form 8a is a participant-reported outcome used to assess the satisfaction with participation in social roles. The participants are asked to rate 8 items on 5-point Likert scales with scores ranging from 8 to 40, where higher scores represents higher satisfaction.

  9. Number of Participants With Abnormalities in Vital Signs, Physical Examinations, Electrocardiogram (ECG), Laboratory Findings, and Injection Site Reactions as a Measure of Safety and Tolerability [ Time Frame: Up to approximately 19 months ]
    Number of participants with abnormalities in vital signs, physical examinations, ECG, laboratory findings and injection site reactions will be reported.

  10. Suicidal Ideation or Behavior Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to 19 months ]
    C-SSRS is a clinician rated assessment of suicidal behavior and / or intent. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 'yes/no' items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Only items with yes responses are listed. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.

  11. Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: Up to 19 months ]
    The AIMS rates 9 items about dyskinesia on scale as 0 = none, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe. It rates 1 item about the participants's awareness of abnormal movements as 0 = no awareness; 1 = aware, no distress; 2 = aware, mild distress; 3 = aware, moderate distress; and 4 = aware, severe distress. It has 2 yes/no questions about dental status. A total score (ranging from 0 to 28) will be calculated as the sum of items 1 to 7.

  12. Barnes Akathisia Rating Scale (BARS) [ Time Frame: Up to 19 months ]
    The BARS assesses akathisia via 1 objective rating and 2 subjective ratings (awareness of restlessness and reported distress related to restlessness); each is scored from 0 to 3 points. It also assesses akathisia via 1 global clinical rating scored from 0 to 5 points. For all items, anchors are provided for each value and higher scores indicate worse akathisia.

  13. Simpson Angus Scale (SAS) [ Time Frame: Up to 19 months ]
    The SAS is led by signs (rather than by symptoms) to measure drug-induced parkinsonism. The modified SAS in this study contains 10 items: 6 items for rigidity (arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, and head rotation); 1 compound item for gait (incorporating gait, posture, and loss of arm swing), and 3 items for tremor, glabellar tap, and salivation. The score ranges between 0 and 4, where the higher score denotes more severe condition of extra pyramidal symptoms.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must meet the diagnostic criteria for schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) for at least 6 months before screening
  • Must be receiving treatment with paliperidone palmitate (as either the paliperidone palmitate 1-month (PP1M) or paliperidone palmitate 3-month (PP3M) formulation), or injectable risperidone, or any oral antipsychotic
  • Must be able, in the opinion of the investigator, to discontinue any antipsychotic medication other than PP1M) or PP3M during the Screening Phase
  • Must have a full Positive and Negative Syndrome Scale (PANSS) score of less than (<) 70 points at screening
  • Must have a body mass index (BMI) between 17 and 40 kilogram (kg)/meter (m)^2 (inclusive) and must have a body weight of at least 47 kg at screening
  • Must be willing to receive gluteal injections of medication during the Double-blind Phase

Exclusion Criteria

  • Must not be receiving any form of involuntary treatment, such as involuntary psychiatric hospitalization, parole-mandated treatment, or court-mandated treatment
  • Must not have attempted suicide within 12 months before screening and must not be at imminent risk of suicide or violent behavior, as clinically assessed by the investigator at the time of screening
  • Must not have a DSM-5 diagnosis of moderate or severe substance use disorder (except for nicotine and caffeine) within 6 months of screening; however, acute or intermittent substance use prior to screening is not exclusionary, depending upon the clinical judgment of the investigator
  • Must not have a history of neuroleptic malignant syndrome or tardive dyskinesia
  • Must not have a history of intolerability or severe reactions to moderate or higher doses of antipsychotic medications and must not have any other factors that would, in the judgment of the investigator, indicate that treatment with moderate or higher doses of paliperidone palmitate would be intolerable or unsafe

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03345342


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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03345342     History of Changes
Other Study ID Numbers: CR108390
R092670PSY3015 ( Other Identifier: Janssen Research & Development, LLC )
2017-001941-28 ( EudraCT Number )
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Paliperidone Palmitate
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine D2 Receptor Antagonists
Dopamine Antagonists
Dopamine Agents