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paliperidone palmitate

Phase 3

Schizophrenia | Small molecule | Psychiatry |Johnson & Johnson|Last Updated: Oct 28, 2024

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindCONTROLLEDBiomarker
Total Trials15
Total Enrollment5,593
FDA Designations
No designations recorded
Clinical Trials (15)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01448720Treatment of Patients With Recently Exacerbated Schizophrenia With Paliperidone PalmitatePHASE3 COMPLETED 142Sep 1, 2011Dec 1, 2013Sep 18, 201412 Brazil, Colombia +1
NCT01281527Paliperidone Palmitate Flexible Dosing in SchizophreniaPHASE3 COMPLETED 1,044Nov 1, 2010Nov 1, 2013Mar 10, 2014127 Austria, Belgium +18
NCT01258920A Study of Paliperidone Palmitate in Japanese Patients With SchizophreniaPHASE3 COMPLETED 201Oct 1, 2010Nov 1, 2012Jun 24, 201429 Japan
NCT01299389An Efficacy and Safety Study of Paliperidone Palmitate in Participants With SchizophreniaPHASE3 COMPLETED 323Oct 1, 2010May 1, 2012Jun 17, 201356 Japan, South Korea +1
NCT01051531A Safety, Tolerability, and Treatment Response Study of Paliperidone Palmitate Administered to Patients With SchizophreniaPHASE3 COMPLETED 546Apr 22, 2010May 17, 2013Oct 28, 202441 Australia, China +7
NCT01081769Prevention of Relapse With Injectable Paliperidone Palmitate Versus Oral AntipsychoticsPHASE3 COMPLETED 769Feb 1, 2010Feb 1, 2013Feb 18, 201594 Austria, Belgium +23
NCT00119756A Safety and Tolerability Study of Paliperidone Palmitate Injected in the Shoulder or the Buttock Muscle in Patients With SchizophreniaPHASE3 COMPLETED 253Jun 1, 2005Nov 1, 2006Jun 8, 2011 -
NCT00210548A Study to Evaluate the Effectiveness and Safety of 3 Doses of Paliperidone Palmitate in Treating Subjects With SchizophreniaPHASE3 COMPLETED 366Apr 1, 2005Jun 1, 2006Jun 8, 2011 -
NCT00111189A Study of the Efficacy (Effectiveness) of Paliperidone Palmitate in the Prevention of Recurrence of the Symptoms of Schizophrenia.PHASE3 COMPLETED 414Feb 1, 2005Feb 1, 2008Jun 20, 201455 United States, Costa Rica +7
NCT00210717A Study to Compare the Effectiveness and Safety of Flexibly Varied Doses of Paliperidone Palmitate and Risperidone in Treating Patients With SchizophreniaPHASE3 COMPLETED 748Feb 1, 2005Apr 1, 2007Jun 8, 2011 -
NCT00101634Efficacy and Safety of a Long Acting Anti-Psychotic Versus Placebo in Patients With SchizophreniaPHASE3 COMPLETED 518Dec 1, 2004Mar 1, 2006Jun 8, 2011 -
NCT00073320Intramuscular Injections of Paliperidone Palmitate in the Arm or Buttock of Subjects With SchizophreniaPHASE3 COMPLETED 88Aug 1, 2003May 1, 2004Apr 27, 2010 -
NCT01606254A Pharmacokinetic and Safety Study of Paliperidone Palmitate (JNS010) in Participants With SchizophreniaPHASE2 COMPLETED 56Jan 1, 2007Apr 1, 2008Jun 5, 20131 Japan
NCT01942382A Clinical Pharmacology Study of JNS010 (Paliperidone Palmitate) in Patients With SchizophreniaPHASE1 COMPLETED 76Apr 1, 2009Mar 1, 2010Sep 16, 2013 -
NCT01110317A Study of Paliperidone Blood Concentrations in Patients With Schizophrenia After Administration of Paliperidone PalmitatePHASE1 COMPLETED 49Jul 1, 2005Mar 1, 2006Apr 27, 2010 -
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Study Endpoints
Primary Endpoints
Change in the Positive and Negative Syndrome Scale (PANSS)
Baseline to 4 months

The neuropsychiatric symptoms of schizophrenia will be assessed using the 30-item PANSS, which provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items). Each question is rated on a scale of 1 (absent) to 7 (extreme).

Improved efficacy for non-acute patients transitioned due to lack of efficacy, as measured by the total PANSS score at endpoint versus baseline.
Baseline to 6 months or early discontinuation
Improved efficacy for acute patients, as measured by the total PANSS score at endpoint versus baseline.
Baseline to 6 months or early discontinuation
Maintained efficacy for non-acute patients transitioned for other reasons based on PANSS score at endpoint versus baseline.
Baseline to 6 months or early discontinuation
Incidence of adverse events as a measure of safety and tolerability
49 Weeks
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 13 or Early Discontinuation
Baseline and Week 13 or early discontinuation

The PANSS is a 30-item scale 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 and ranges from 30 to 210, higher scores indicate worsening.

Treatment response will be evaluated by findings from the PANSS-a 30-item questionnaire that is administered to the patient by a qualified person (ie, rater) to measure the presence/absence and severity of positive and negative symptoms of schizophrenia
Treatment response will be evaluated at 5 times during the study (Day 1, day 38, day 98, day 188, day 368 and day 548).
Time to First Relapse Event
from baseline (Day 1 of core phase) up to maximally 24 months.

Number of days from baseline (day 1 of core phase) to relapse as evaluated according the Csernansky criteria. A patient was considered to have relapsed if they met one or more of the following criteria: (1) psychiatric hospitalization; (2) an increase in the level of psychiatric care and an increase of 25 percent (%) from baseline in the Positive And Negative Syndrome Score (PANSS) total score (or an increase of 10 points if the baseline score was 40 or less); (3) deliberate self-injury; (4) suicidal or homicidal ideation that was clinically significant in the investigator's judgment; (5) violent behavior resulting in clinically significant injury to another person or property damage; (6) substantial clinical deterioration, defined as a change score of 6 ("much worse") or 7 ("very much worse") on the Clinical Global Impressions Scale (CGI-C); and/or (7) the required dose of the antipsychotic exceeds the maximum approved dose.

Number of Participants With a Relapse Event
from baseline (Day 1 of core phase) up to maximally 24 months

Number of participants with a relapse event with relapses evaluated according the Csernansky criteria. A patient was considered to have relapsed if they met one or more of the following criteria: (1) psychiatric hospitalization; (2) an increase in the level of psychiatric care and an increase of 25% from baseline in the PANSS total score (or an increase of 10 points if the baseline score was 40 or less); (3) deliberate self-injury; (4) suicidal or homicidal ideation that was clinically significant in the investigator's judgment; (5) violent behavior resulting in clinically significant injury to another person or property damage; (6) substantial clinical deterioration, defined as a change score of 6 ("much worse") or 7 ("very much worse") on the Clinical Global Impressions Scale (CGI-C); and/or (7) the required dose of the antipsychotic exceeds the maximum approved dose.

Safety evaluation (e.g. incidence of adverse events) between start and finish of the trial
The change in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from the beginning to the end of the double-blind treatment period or to the last post-randomization assessment.
The primary efficacy criteria for this study is the time from randomization to the first recurrence event during the double-blind recurrence prevention period
After 68 relapse events
The change in the total score of the Positive and Negative Syndrome Scale (PANSS) from the beginning to the end of the double-blind treatment period or to the last post-randomization assessment.
Change in total PANSS score from baseline to the end of the double blind treatment period.
To explore the comparability of pharmacokinetic parameter estimates of paliperidone and paliperidone palmitate between the 2 injection sites.
Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 8
Day 8

The pre-dose plasma concentration (Cpredose) at Day 8 is defined as the plasma concentration obtained before a dose is given on Day 8. The mean Cpredose at Day 8 was measured in nanogram per milliliter (ng/ml).

Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 36
Day 36

The Cpredose at Day 36 is defined as the plasma concentration obtained before a dose is given on Day 36. The mean Cpredose at Day 36 was measured in ng/ml.

Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 64
Day 64

The Cpredose at Day 64 is defined as the plasma paliperidone concentration obtained before a dose is given on Day 64. The mean Cpredose at Day 64 was measured in ng/ml.

Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 92
Day 92

The Cpredose at Day 92 is defined as the plasma paliperidone concentration obtained after the treatment interval of the study drug (that is 4 weeks) passed after the final dose (Day 92). The mean Cpredose at Day 92 was measured in ng/ml.

Maximum Observed Plasma Concentration (Cmax) of Paliperidone
Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal

The Cmax is defined as maximum observed analyte concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Paliperidone
Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal

The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal

The AUCtau is a measure of the plasma paliperidone concentration from time zero to end of dosing interval. It is used to characterize drug absorption.

Plasma Paliperidone Concentration at Steady State (Css av)
Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal

The Css av is defined as value of average analyte concentration at steady-state (after 4 Intramuscular Injections of Paliperidone Palmitate).

Paliperidone Plasma Decay Half-Life (t1/2)
Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 8
Day 8

The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 \[none, normal\]; 1 \[Very Mild\]; 2 \[Mild\]; 3 \[Moderate\]; 4 \[severe\]).

Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 22
Day 22

The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 \[none, normal\]; 1 \[Very Mild\]; 2 \[Mild\]; 3 \[Moderate\]; 4 \[severe\]).

Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 50
Day 50

The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 \[none, normal\]; 1 \[Very Mild\]; 2 \[Mild\]; 3 \[Moderate\]; 4 \[severe\]).

Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 78
Day 78

The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 \[none, normal\]; 1 \[Very Mild\]; 2 \[Mild\]; 3 \[Moderate\]; 4 \[severe\]).

Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 92
Day 92

The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 \[none, normal\]; 1 \[Very Mild\]; 2 \[Mild\]; 3 \[Moderate\]; 4 \[severe\]).

Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 120
Day 120

The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 \[none, normal\]; 1 \[Very Mild\]; 2 \[Mild\]; 3 \[Moderate\]; 4 \[severe\]).

Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 162
Day 162

The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 \[none, normal\]; 1 \[Very Mild\]; 2 \[Mild\]; 3 \[Moderate\]; 4 \[severe\]).

Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 218
Day 218

The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 \[none, normal\]; 1 \[Very Mild\]; 2 \[Mild\]; 3 \[Moderate\]; 4 \[severe\]).

Plasma concentration of unchanged drug (Paliperidone palmitate)
Days 1 to 190
Plasma concentration of active metabolite (paliperidone)
Days 1 to 190
Plasma concentration of enantiomer of paliperidone palmitate (R078543)
Days 1 to 190
Plasma concentration of enantiomer paliperidone palmitate (R078544)
Days 1 to 190
Maximum Observed Plasma Concentration (Cmax) of paliperidone palmitate
Days 1 to 190

The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax) of paliperidone palmitate
Days 1 to 190

The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of paliperidone palmitate
Days 1 to 190

The Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) is a measure of the plasma paliperidone concentration from time zero to end of dosing interval. It is used to characterize drug absorption.

Number of participants with adverse events
Up to Day 190
Determination of the concentration of paliperidone in blood samples obtained from patients.
Predose at specified time points (Days 18, 20, 22, 29, 46, 50, 85, 92, 99, 106, 120, 134, 148, 162, and 176) during the study through Day 176 or the time of early withdrawal from the study.
Secondary Endpoints
Change from Baseline in global severity of illness using the clinical global impression - severity (CGI-S) scores
Baseline to 4 months
Change from Baseline in the personal and social performance scale (PSP)
Baseline to 4 months
Change from baseline in Clinical Global Impression-Severity Scale [CGI-S]
Baseline, week 1, month 1, 2, 3 and 6
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Paliperidone palmitateEXPERIMENTAL -
PlaceboPLACEBO_COMPARATOR -
Oral AntipsychoticsACTIVE_COMPARATORoral antipsychotics daily treatment according to local label for maximally 24 months
001EXPERIMENTALPaliperidone Palmitate 25, 50, 75 or 100 mg eq every 4 wk for up to 24 mo
002PLACEBO_COMPARATORPlacebo Placebo every 4 wk up to 24 mo
Paliperidone palmitate 50 mgEXPERIMENTALPaliperidone palmitate 50 milligram (mg) intramuscular (into the muscle) injection on Days 1, 8, 36 and 64.
Paliperidone palmitate 100 mgEXPERIMENTALPaliperidone palmitate 100 mg intramuscular injection on Days 1, 8, 36 and 64.
Paliperidone palmitate 150 mgEXPERIMENTALPaliperidone palmitate 150 mg intramuscular injection on Days 1, 8, 36 and 64.
Paliperidone palmitate 150/ 50 mgEXPERIMENTALPaliperidone palmitate 150 mg intramuscular injection on Day 1 and paliperidone palmitate 50 mg intramuscular injection on Days 8, 36 and 64.
Treatment AEXPERIMENTALParticipants will receive 4 injections of paliperidone palmitate 150 milligram in the deltoid muscle on Days 1, 8, 36, and 64.
Treatment BEXPERIMENTALParticipants will receive 4 injections of paliperidone palmitate 75 milligram in the deltoid muscle on Days 1, 8, 36, and 64.
Treatment CEXPERIMENTALParticipants will receive 4 injections of paliperidone palmitate 75 milligram in the gluteal muscle on Days 1, 8, 36, and 64.
Interventions
NameTypeDescription
Paliperidone palmitateDRUGType=exact number, unit=mg, number=150, 100, 75 mg equivalent (eq), form=suspension for injection, route=intramuscular use. One IM injection of 150 mq on Day 1, 100 mg eq. on Day 8 (+/- 4 days), and 75 mg eq. is recommended on Days 36, 64, and 92.
PlaceboDRUGMatching Placebo will be given intramuscularly (Injection of a drug into a muscle) on Day 1, Day 8, Day 36 and Day 64. Participants who complete double-blind period or discontinued early from double-blind period will have follow-up visits during post-observational period at Weeks 4, 8 and 12 after the last injection in the double-blind period. Participants will not receive any study drug during post-observational period.
paliperidone palmitate injectionDRUGinjection with 150 mg equivalent on Day 1, 100 mg equivalent on Day 8, 75 mg equivalent on Day 38 and flexible dosing with 25, 50, 75, 100 or 150 mg equivalent once monthly thereafter
oral antipsychoticsDRUGdaily treatment according to local label for maximally 24 months
paliperidone palmitate 100 mgDRUGPatients will receive a single paliperidone palmitate 100 mg equivalent injection in the gluteal or deltoid muscle on Day 1, 8, 36, and 64.
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Eligibility Criteria
Age Range18 Years — 49 Years
SexALL
Healthy VolunteersNo
Study Sites12

Inclusion Criteria: * Be otherwise healthy on the basis of physical examination and vital signs at Screening (Baseline) and have a current diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) for at least 1 year before screening and ...

Countries:BrazilColombiaMexicoAustriaBelgiumCroatiaDenmarkEstoniaFranceGermanyGreeceHungaryIsraelLatviaLithuaniaNetherlandsPortugalSpainSwedenSwitzerlandTurkey (Türkiye)UkraineUnited KingdomJapanSouth KoreaTaiwanAustraliaChinaHong KongMalaysiaNew ZealandPhilippinesThailandBulgariaCzechiaEgyptJordanPolandRomaniaRussiaSlovakiaSouth AfricaUnited StatesCosta Rica
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