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NCT01190254

Fixed Dose Efficacy and Safety Study of Asenapine for the Treatment of Schizophrenia in Adolescents (P05896)

Completed Phase 3 Results posted Last updated 21 May 2024
What this trial tests

Phase 3 trial testing asenapine 2.5 mg in Schizophrenia, Paranoid in 306 participants. Completed in 1 April 2013.

Timeline
28 September 2010
Primary endpoint
10 March 2013
1 April 2013

Quick facts

Lead sponsorOrganon and Co
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment306
Start date28 September 2010
Primary completion10 March 2013
Estimated completion1 April 2013

Drugs / interventions tested

Conditions studied

Sponsor

Organon and Co — full company profile →

Who can join

Adults 12 to 17, any sex, with Schizophrenia, Paranoid or Schizophrenia, Disorganized. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 56 Primary · Baseline and Day 56

The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assi

GroupValue95% CI
Placebo-17.8-20.7 – -13.5
Asenapine 2.5 mg BID-23.7-25.5 – -18.2
Asenapine 5.0 mg BID-25.5-26.3 – -19.1
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Day 56 Secondary · Baseline and Day 56

Change from baseline in CGI-S score at Day 56 is the Key Secondary Outcome Measure. CGI-S is a 7-point scale for assessing the global severity of the participant's illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

GroupValue95% CI
Placebo-0.8-1.0 – -0.6
Asenapine 2.5 mg BID-1.1-1.2 – -0.8
Asenapine 5.0 mg BID-1.3-1.4 – -1.0
Change From Baseline in PANSS Positive Subscale Score at Day 56 Secondary · Baseline and Day 56

This measure reports results for the 7 items of the positive subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS positive subscale score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measu

GroupValue95% CI
Placebo-6.0-7.1 – -4.7
Asenapine 2.5 mg BID-7.9-8.7 – -6.3
Asenapine 5.0 mg BID-9.1-9.3 – -6.9
Change From Baseline in PANSS Negative Subscale Score at Day 56 Secondary · Baseline and Day 56

This measure reports results for the 7 items of the negative subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS negative subscale score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported

GroupValue95% CI
Placebo-3.4-4.3 – -2.3
Asenapine 2.5 mg BID-4.8-5.5 – -3.5
Asenapine 5.0 mg BID-4.9-5.5 – -3.5
Change From Baseline in PANSS Positive and Negative Subscale Scores Combined at Day 56 Secondary · Baseline and Day 56

This measure reports results for the combined positive subscale (7 items) and negative subscale (7 items) of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each of the total 14 items in the combined positive and negative subscales, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS positive and negative subscale

GroupValue95% CI
Placebo-9.4-11.2 – -7.2
Asenapine 2.5 mg BID-12.7-14.0 – -9.9
Asenapine 5.0 mg BID-14.0-14.4 – -10.5
Change From Baseline in PANSS General Psychopathology Subscale Score at Day 56 Secondary · Baseline and Day 56

This measure reports results for the 16 items of the general psychopathology subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS general psychopathology subscale score for each participant was calculated as the sum of the rating assigned to each of the 16 subscale items, and ranged from 16 to 112 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in sym

GroupValue95% CI
Placebo-8.5-9.7 – -6.2
Asenapine 2.5 mg BID-10.9-11.9 – -8.3
Asenapine 5.0 mg BID-11.5-12.0 – -8.5
Change From Baseline in PANSS Marder Positive Symptoms Factor Score at Day 56 Secondary · Baseline and Day 56

This measure reports results for the 8 items of the Marder positive symptoms factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items (Marder et al. J Clin Psychiatry 1997;58(12):538-46). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder positive symptoms factor score for each participant was calculated as the sum of the rating as

GroupValue95% CI
Placebo-6.1-7.3 – -4.9
Asenapine 2.5 mg BID-7.9-8.7 – -6.2
Asenapine 5.0 mg BID-8.9-9.2 – -6.8
Change From Baseline in PANSS Marder Negative Symptoms Factor Score at Day 56 Secondary · Baseline and Day 56

This measure reports results for the 7 items of the Marder negative symptoms factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder negative symptoms factor score for each participant was calculated as the sum of the rating assigned to each of the 7 applicable Marder factor

GroupValue95% CI
Placebo-3.7-4.6 – -2.6
Asenapine 2.5 mg BID-5.2-5.9 – -3.9
Asenapine 5.0 mg BID-5.3-5.9 – -3.9
Change From Baseline in PANSS Marder Disorganized Thoughts Factor Score at Day 56 Secondary · Baseline and Day 56

This measure reports results for the 7 items of the Marder disorganized thoughts factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder disorganized thoughts factor score for each participant was calculated as the sum of the rating assigned to each of the 7 applicable Marder factor items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms

GroupValue95% CI
Placebo-3.4-4.3 – -2.6
Asenapine 2.5 mg BID-4.3-5.2 – -3.5
Asenapine 5.0 mg BID-4.8-5.2 – -3.5
Change From Baseline in PANSS Marder Hostility/Excitement Factor Score at Day 56 Secondary · Baseline and Day 56

This measure reports results for the 4 items of the Marder hostility/excitement factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder hostility/excitement factor score for each participant was calculated as the sum of the rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms.

GroupValue95% CI
Placebo-2.8-3.3 – -1.8
Asenapine 2.5 mg BID-3.8-4.3 – -2.8
Asenapine 5.0 mg BID-3.8-4.1 – -2.6
Change From Baseline in PANSS Marder Anxiety/Depression Factor Score at Day 56 Secondary · Baseline and Day 56

This measure reports results for the 4 items of the Marder anxiety/depression factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder anxiety/depression factor score for each participant was calculated as the sum of the rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. The

GroupValue95% CI
Placebo-1.8-2.3 – -1.2
Asenapine 2.5 mg BID-2.4-2.7 – -1.6
Asenapine 5.0 mg BID-2.7-2.8 – -1.8
Total PANSS 30% Responders Secondary · Baseline up to Day 56

A Total PANSS 30% responder was defined as a participant who had a reduction from baseline of at least 30% in the PANSS Total score at the last available assessment of the study for that participant (i.e., endpoint). The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The Total score is the sum of the ratings for the individual items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms.

GroupValue95% CI
Placebo36
Asenapine 2.5 mg BID48
Asenapine 5.0 mg BID51

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 30 days after the last dose of study drug. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 3/102 (3%)
Deaths:
Asenapine 2.5 mg BID
Serious: 3/98 (3%)
Deaths:
Asenapine 5.0 mg BID
Serious: 3/106 (3%)
Deaths:

Serious adverse events (4 terms)

ReactionSystemPlaceboAsenapine 2.5 mg BIDAsenapine 5.0 mg BID
SchizophreniaPsychiatric disorders
Hallucination, auditoryPsychiatric disorders
PneumoniaInfections and infestations
Typhoid feverInfections and infestations
Other adverse events (8 terms — click to expand)

ReactionSystemPlaceboAsenapine 2.5 mg BIDAsenapine 5.0 mg BID
SomnolenceNervous system disorders
SedationNervous system disorders
InsomniaPsychiatric disorders
HeadacheNervous system disorders
NauseaGastrointestinal disorders
AkathisiaNervous system disorders
DizzinessNervous system disorders
Hypoaesthesia oralGastrointestinal disorders

Most-reported serious reactions: Schizophrenia, Hallucination, auditory, Pneumonia, Typhoid fever.

Data from ClinicalTrials.gov NCT01190254 adverse events section.

Sponsor's own description

This study is designed to evaluate whether asenapine, which is approved by the United States Food and Drug Administration (US FDA) for acute treatment of schizophrenia in adults, is also effective in adolescents with schizophrenia. Participants who qualify for the study will be randomly assigned to receive a fixed dose of asenapine (either 2.5 mg or 5 mg twice daily \[BID\]) or placebo for 8 weeks. Throughout the study, observations will be made on each participant at various times to assess the efficacy and safety of the study treatment. The primary objective of the trial is to demonstrate significant superiority of at least one asenapine dose to placebo, as measured by the change from baseline of the Positive and Negative Syndrome Scale (PANSS) total score at Day 56.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Safety and Efficacy from an 8 Week Double-Blind Trial and a 26 Week Open-Label Extension of Asenapine in Adolescents with Schizophrenia.
    Findling RL, Landbloom RP, Mackle M, Pallozzi W, et al · · 2015 · cited 33× · PMID 26091193 · DOI 10.1089/cap.2015.0027
  2. Asenapine versus placebo for schizophrenia.
    Hay A, Byers A, Sereno M, Basra MK, et al · · 2015 · cited 10× · PMID 26599405 · DOI 10.1002/14651858.cd011458.pub2
  3. Asenapine Treatment in Pediatric Patients with Bipolar I Disorder or Schizophrenia: A Review.
    Stepanova E, Grant B, Findling RL. · · 2018 · cited 6× · PMID 29170943 · DOI 10.1007/s40272-017-0274-9
  4. Asenapine pharmacokinetics and tolerability in a pediatric population.
    Dogterom P, Riesenberg R, de Greef R, Dennie J, et al · · 2018 · cited 5× · PMID 30214156 · DOI 10.2147/dddt.s171475

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing