| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 13.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10039621 |
| E.1.2 | Term | Schizoaffective disorder |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To evaluate the efficacy of paliperidone palmitate compared with placebo in the delay of relapse of the symptoms of schizoaffective disorder
• To assess the safety and tolerability of paliperidone palmitate in subjects with schizoaffective disorder |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate symptom change as measured by the Positive and Negative Syndrome Scale (PANSS) total and PANSS factor scores during the double-blind Relapse Prevention Period with paliperidone palmitate compared with placebo
• To evaluate illness severity change as measured by Clinical Global Impression of Severity for Schizoaffective Disorder (CGI-S-SCA) during the double-blind Relapse Prevention Period with paliperidone palmitate compared with placebo
• To evaluate change in subject functioning using the Personal and Social Performance Scale (PSP) during the double-blind Relapse Prevention Period with paliperidone palmitate compared with placebo
• To evaluate change in subject medication satisfaction using the Medication Satisfaction Questionnaire (MSQ) during the double-blind Relapse Prevention Period with paliperidone palmitate compared with placebo
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Men or women >= 18 years of age
2. Subjects must sign the study informed consent document indicating that they understand the purpose
of and procedures required for the study and are willing to participate in the study. Note: It is
acceptable to have additional signatures if required by local regulations. If a subject has an appointed
legal representative, both the representative and the subject will sign the form. In addition, if the
subject or legally-acceptable representative is unable to read or write, it is acceptable to obtain
consent orally with the presence of an impartial witness who should personally date and sign the
informed consent form. Subjects who are unable to provide their own consent (in writing or orally) or
who have been involuntarily committed to psychiatric hospitalization are not eligible to enroll in the
study.
3. Women must be postmenopausal for at least 2 years, surgically sterile, abstinent, or agree to practice
an effective method of birth control if they are sexually active before entry and throughout the study
(effective methods of birth control include prescription hormonal contraceptives, intrauterine devices,
double-barrier method, and male partner sterilization). Women of childbearing potential must have a
negative urine pregnancy test result at screening.
4. Subjects must have lifetime and current diagnosis of schizoaffective disorder (DSM-IV 295.70), as
confirmed by the SCID at screening.
5. Subjects must be experiencing an acute exacerbation of psychotic symptoms no less than 4 days and
no more than 4 weeks in duration prior to screening.
6. At screening, subjects must have a score of ≥4 on at least 3 of the following 9 PANSS items:
Delusions (P1), Conceptual Disorganization (P2), Hallucinatory behavior (P3), Excitement (P4), Suspiciousness/Persecution (P6), Hostility (P7), Tension (G4), Uncooperativeness (G8), and Poor Impulse Control (G14).
7. At screening, subject must have a score of ≥16 on YMRS and/or a score of ≥16 on the HAM-D-21.
8. Subjects must be healthy based on physical examinations, electrocardiogram (ECG), laboratory tests,
medical history, and vital signs measurements.
9. Body mass index (BMI) [weight (kg)/height (m²)] between 17.0 and 40.0, inclusive.
10. Subjects must be cooperative and reliable, agree to receive regular injections, and be willing and able
to adhere to the prohibitions and restrictions specified in this protocol.
11. To participate in the optional pharmacogenomic component of this study, subjects (or their legallyacceptable
representative) must have signed the informed consent form for pharmacogenomic
research indicating willingness to participate in the pharmacogenomic component of the study (where
local regulations permit). Refusal to give consent for this component does not exclude a subject from
participation in the clinical study.
Stabilization Criteria to Enter double-blind Relapse Prevention Period:
In addition, to be eligible for randomization to the double-blind Relapse Prevention Period, all of the
following stabilization criteria must be met at each visit during the 12-week Stabilization Period:
• PANSS total score ≤70
• YMRS and HAM-D-21 ≤12
− A single excursion in mood symptoms (YMRS and/or HAM-D-21 between 13 and 17 and not
requiring hospitalization) will be permitted during the first 8 weeks of the Stabilization Period (i.e.,
up to Day 148/Visit 8). After such an excursion, the subject should be brought in for an unscheduled
visit and re-evaluated within 7 days and must again meet stabilization criteria for mood symptom
ratings (i.e., YMRS and HAM-D-21 ≤12). If the YMRS and HAM-D-21 ratings are not ≤12 the
subject will not be eligible for randomization. |
|
| E.4 | Principal exclusion criteria |
1. Subjects who are unable to provide their own consent (in writing or orally) or are involuntarily committed to a psychiatric hospital.
2. Women who are pregnant (as confirmed by a urine pregnancy test performed at screening), planning to become pregnant, or breast-feeding.
3. Subject is an employee or family member of the investigator or institution.
4. Johnson & Johnson employees or their family members.
5. Subjects with a urine drug screen that is positive for cocaine, opiates, phenylcyclohexylpiperidine (PCP), or amphetamines. Psychiatric history
6. Subjects meeting the DSM-IV criteria for major depressive disorder, bipolar disorder, or schizophrenia
7. Subjects currently meeting criteria for any other Axis I diagnosis except substance abuse.
8. Subjects with an Axis II diagnosis of Mental Retardation or Borderline Personality Disorder.
9. Subjects meeting the DSM-IV criteria for substance dependence (except for nicotine and caffeine dependence) in the 3 months before the screening visit.
10. Subjects who have attempted suicide within 12 months before the screening visit or are at imminent risk of suicide or violent behavior according to the investigator’s clinical judgment.
11. Subjects who are in their first episode of psychosis (no prior history of psychotic symptoms)
12. Subjects with a history of receiving electroconvulsive therapy in the 3 months before the screening visit
13. Subjects with a history of hypersensitivity to or intolerance of paliperidone, risperidone, or 20% Intralipid (placebo) or any of their excipients (eg, soybean oil, egg yolks, phospholipids, glycerol)
14. Subjects who have participated in a clinical investigation or received an experimental therapy within 30 days before the screening visit or have participated in >2 clinical studies within the last 12 months
15. Subjects who previously were enrolled in this study
16. Subjects who received long-acting antipsychotic medication within 2 injection cycles prior to the screening visit
17. Subjects who received therapy with clozapine within 3 months of the screening visit with the exception of low dose clozapine used for treatment of insomnia.
18. Subjects with a history of neuroleptic malignant syndrome
19. Subjects with a previous history of lack of response to antipsychotic medication. Lack of response is
defined by failure to respond to 2 adequate trials of different antipsychotic medications; an adequate
trial is defined as a minimum of 4 weeks at the subject’s maximum tolerated dose
20 Subjects who are:
receiving therapy with both MS and AD; or
receiving therapy with MS or AD that has been initiated or changed in dose within 30 days prior to screening.
Exceptions: Subjects who meet the following can enter the study:
– have been on a generally stable dose of MS or AD (eg, no more than
5 daily doses differing from the subject’s usual dose within 30 days
prior to screening); or
– have been essentially free of MS or AD (eg, no more than 5 daily
doses of either MS or AD within 30 days prior to screening).
21. Subjects receiving therapy with carbamazepine
22. Subjects receiving therapy with monoamine oxidase inhibitors
Somatic history
23. 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, including:
− Heart rate <50
− Demonstration of repeated prolonged QTc Fridericia interval >450 msec, as measured on more than
one ECG (either during screening, or from prior medical record)
− the following cardiac conditions: sick sinus syndrome, complete AV block, congestive heart failure,
polymorphic ventricular tachycardia
− clinically relevant hypocalcemia, hypokalemia or hypomagnesemia;
− concomitant use of drugs that prolong the QTc interval (including Class 1A (eg, quinidine,
procainamide) or Class III (eg, amiodarone, sotalol) antiarrhythmic medications; presence of
congenital prolongation of the QT interval (Romano-Ward Syndrome, Jervell and Lange-Nielsen
syndrome)
24. Subjects with a serious and/or unstable neurological disease, including but not limited to Alzheimer’s
disease, vascular dementia, Parkinson’s disease, intracranial lesions, hydrocephalus, significant head
trauma, or seizure disorder
25. Relevant history of or current presence of any significant and/or unstable cardiovascular, respiratory,
neurological (including seizures or significant cerebrovascular), renal, hepatic, hematologic, endocrine,
immunologic, morbid obesity, or other systemic disease |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint for this study is the time between subject randomization to treatment and the first occurrence of a relapse during the Relapse Prevention Period. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time between subject randomization to treatment and the first occurrence of a relapse during the 15-month double-blind Relapse Prevention Period compare paliparidone palmitate treatment with placebo.
|
|
| E.5.2 | Secondary end point(s) |
During relapse prevention period, compare paliparidone palmitate treatment with placebo in symptom change as measured by the Positive and Negative Syndrome Scale (PANSS) total and PANSS factor scores, illness severity change as measured by Clinical Global Impression of Severity for Schizoaffective Disorder (CGI-S-SCA), change in subject functioning using the Personal and Social Performance Scale (PSP), change in subject medication satisfaction using the Medication Satisfaction Questionnaire (MSQ), change in mood symptoms as measured by YMRS (in subjects with YMRS>=16 at enrollment) and HAM-D-21 (in subjects with HAM-D-21>=16 at enrollment) and HAM-D-17 (in subjects with HAM-D-17>=16 at enrollment.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Monthly assessment during 15-month relapse prevention period.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| India |
| Malaysia |
| Philippines |
| Russian Federation |
| South Africa |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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