| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Recently-Diagnosed Schizophrenia |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039626 |
| E.1.2 | Term | Schizophrenia |
|
| 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 |
The primary objective of this study is to assess the efficacy of paliperidone palmitate
compared with oral risperidone in delaying time to relapse in subjects recently
diagnosed with schizophrenia who are at high risk of relapse. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are the following:
• Evaluation of the impact of paliperidone palmitate compared with oral risperidone
with respect to personal and social functioning (Personal and Social Performance
Scale; PSP).
• Assessment of the safety and tolerability of paliperidone palmitate in this study
population through monitoring adverse events, laboratory tests, vital signs including
weight, physical examinations, movement disorders (Extrapyramidal Symptom
Rating Scale-abbreviated, ESRS-A), sexual functioning (Arizona Sexual Experiences
Scale; ASEX), and suicidality (InterSePT Scale for Suicidal Thinking-Plus, ISSTPlus). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Subjects must be men or women between 18 and 35 years of age, inclusive.
• Subjects must be, in the opinion of the investigator, able to understand the informed consent form approved by the Institutional Review Board (IRB) or Independent Ethics Committee (IEC), as appropriate. All 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. In addition, reasonable efforts should be made to provide information about the study to a subject’s designated contact person. Note: It is acceptable to have additional signatures if required by local regulations. In addition, where permitted, if a subject has an appointed legal representative, both the representative and the subject must sign the form. Subjects who are unable to provide their own consent or who have been involuntarily committed to psychiatric hospitalization are not eligible to enroll in the study.
• Subjects must have a current diagnosis of schizophrenia [paranoid type (295.30), disorganized type (295.10), undifferentiated type (295.90), or residual type (295.60)] based upon the SCID-CV according to criteria given in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV).
• Subjects must have had a first diagnosis of any psychotic disorder within 5 years before screening and must currently meet diagnostic criteria for schizophrenia as confirmed by administration of the SCID CV at the screening visit. Prior medical records, written documentation, or verbal information (with accompanying written documentation) obtained from previous psychiatric providers must be provided.
• Subjects must have had 3 periods of breakthrough symptoms within the previous 24 months, including 1 such period within the previous 6 months. These breakthrough symptoms must have necessitated a change in subject care (eg, hospitalization due to relapse, increases or additions of psychotropic medications, and/or increases in the frequency or intensity of subject contact required to maintain outpatient status. Other indicators presented by the clinical investigator will be reviewed on a case-by-case basis by the medical monitor).
• Subjects must have a CGI-S score ≥4 at Screening and at Stabilization Phase baseline.
• Subjects must have scores of at least 4 ("Moderate") on at least 2 of the following PANSS assessment items at Screening and at the Stabilization Phase baseline visit:
• G9, Unusual thought content
• P1, Delusions
• P3, Hallucinatory behavior
• P4, Excitement
• P5, Grandiosity
• P6, Suspiciousness/persecution
• Subjects may have a historical diagnosis of alcohol or substance abuse, excluding intravenous (IV) use.
• Subjects must be healthy based on physical examination, medical history, vital signs, and 12-lead ECG performed at screening. If there are abnormalities, the subject may be included only if, after discussion with the medical monitor, the investigator judges the abnormalities or deviations from normal not to be clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initialed by the investigator.
• Subjects must be healthy based on clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initialed by the investigator.
• Women must be postmenopausal (for at least 2 years), surgically sterile (hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent, or if sexually active, be practicing a highly effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel], male partner sterilization) before entry, and must agree to continue to use the same method of contraception throughout the study.
• Women of childbearing potential must have a negative urine β-human chorionic
gonadotropin (β-hCG) dipstick pregnancy test at screening and at stablilization
baseline.
• Subjects must be cooperative and reliable, agree to receive regular injections, and be willing/able to adhere to the prohibitions and restrictions specified in this protocol. |
|
| E.4 | Principal exclusion criteria |
• Subjects who are unable to provide their own consent or are involuntarily committed to psychiatric hospitalization
• Subjects who have attempted suicide within 12 months before screening or are at imminent risk of suicide or violent behavior, as clinically assessed by the investigator at time of screening
• Subjects who have a positive urine drug screen test for barbiturates, cocaine, amphetamines, or opiates at screening; subjects may be re-screened 30 days after a positive drug screen.
• Subjects who are in their first episode of psychosis
• Subjects with a psychiatric diagnosis that is due to direct pharmacological effect of a substance (eg, a drug of abuse or medication) or a general medical condition (eg, clinically notable hypothyroidism).
• Subjects currently meeting criteria for any other Axis I diagnosis except substance abuse
• Subjects who are treatment-resistant in the judgment of the Investigator
• Subjects with an Axis II diagnosis of Mental Retardation or Borderline Personality Disorder
• Subjects meeting the DSM-IV definition of substance dependence (except for nicotine and caffeine dependence) within 6-months prior to entry; Subjects with current substance use or abuse, with the exception of intravenous drug use, will be allowed to enroll.
• Subjects with a history of neuroleptic malignant syndrome
• Subjects with known allergies, hypersensitivity (anaphylaxis-type reaction), or intolerance to paliperidone palmitate, risperidone, Risperdal®, Risperdal® Consta®, or INVEGA® or its excipients (refer to Section 13.1, Physical Description of Study Drug(s)
• Subjects with evidence of clinically significant cardiovascular, renal, hepatic, gastrointestinal, neurological, endocrine, metabolic or pulmonary disease within the past 6 months (as determined by medical history, clinical laboratory or ECG results, or physical examination) that would increase the risk associated with taking study medication or would confound the interpretation of the study
• Subjects who received an investigational drug (including vaccines) or used an investigational medical device within 30 days of SPD 1 (SPV1, stabilization baseline), are currently enrolled in an investigational study, have planned use of other investigational drugs during the timeframe of the study, or have participated in more than 2 clinical trials in the past year
• Subjects who received LAT treatment within 2 injection cycles prior to screening
• Subject who received treatment with clozapine within 3 months of SPD 1
• Subjects receiving therapy with carbamazepine
• Women who are pregnant or breast-feeding, or planning to become pregnant
• Subjects with any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
• Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator
• Subjects who have a pre-planned surgery or procedure that would interfere with the conduct of the study
• Subjects with a previous history, in the clinician’s judgment, of inadequate response to 9 OH risperidone (paliperidone) or risperidone |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
A subject will be considered to have completed the study if he or she has completed assessments at Week 104, the end of the Relapse Prevention Phase.
If a subject's study treatment must be discontinued before the end of the treatment regimen, this will not result in automatic withdrawal of the subject from the study.
|
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| 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 | Yes |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 11 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
| This is provided in the protocol - Section 16.9.1 |
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | 7 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 7 |
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