| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | HLGT |
| E.1.2 | Classification code | 10039628 |
| E.1.2 | Term | Schizophrenia and other psychotic 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 |
Primary Objective
The primary objective is to evaluate the efficacy via the changes from baseline in the total Positive and Negative Syndrome Scale (PANSS) score of three fixed doses of JNJ-37822681 compared with placebo after 6 weeks’ treatment in subjects with schizophrenia. |
|
| E.2.2 | Secondary objectives of the trial |
· To evaluate the safety of three fixed doses of JNJ-37822681,
· To assess the effect on the changes from baseline in the PANSS subscales and the CGI S of illness
· To assess the effect on the changes from baseline in BMI, body weight, plasma metabolic endpoints (fasting total cholesterol, triglycerides, high-density lipoproteins (HDL), low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), free fatty acids, HbA1c, glucose, and insulin) and SWN
· To assess the acute response relative to placebo and olanzapine using the changes from baseline in the NOSIE in the first 2 weeks
· To explore the pharmacokinetics and the relationship between pharmacokinetics and efficacy parameters (e.g., change in PANSS scores) and safety parameters (e.g., treatment emergent EPS, or other adverse events),
· To explore genes/genotypes that may be related to clinical response, non-response, to safety parameters, or to pharmacokinetics of JNJ 37822681.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Male and female between 18 and 65 years of age, inclusive
• BMI maximum 40 kg/m2, inclusive (BMI = weight/height2)
• Subjects must have been diagnosed with schizophrenia according to
DSM-IV (295.10, 295.20, 295.30, 295.60, 295.90) at least 1 year prior to
screening.
• Subjects must have signed an informed consent document indicating that
they understand the purpose of and procedures required for the study and
are willing to participate in the study. It is acceptable to have additional
signatures if required by local regulations. 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 be experiencing an acute exacerbation of less than
6 months duration, with a PANSS total score at screening between
70 and 120 inclusive and at baseline of between 60 and 120 inclusive.
• Women must meet one of the following:
– postmenopausal (amenorrhoea for at least 12 months and follicle
stimulating hormone (FSH) concentrations of >40 MIU/mL at
screening),
– surgically sterile (have had a hysterectomy or bilateral oophorectomy,
tubal ligation, or otherwise be incapable of pregnancy),
– abstinent (at the discretion of the investigator/per local regulations),
– or if sexually active, be practicing an effective method of birth control
(e.g., prescription oral contraceptives, contraceptive injections,
contraceptive patch, intrauterine device, double-barrier method [e.g.,
condoms, diaphragm, or cervical cap with spermicidal foam, cream,
or gel], male partner sterilization) as local regulations permit,
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) pregnancy test at screening and at
baseline before receiving the study drug..
• Subjects must agree to voluntary hospitalization for a minimum of
14 days.
• Subjects must be willing and able to fill out self-administered
questionnaires.
• Subjects must be able to be compliant with self-administration of
medication, or have consistent help/support available.
• Subjects themselves, or caregivers or relatives with whom they are
living, have to be reachable by phone on a regular basis.
• Subjects must be willing and able to adhere to the prohibitions and
restrictions specified in this protocol.
• To participate in the optional pharmacogenomic component of this study,
subjects (or their legally acceptable 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 consent for this
component does not exclude a subject from participation in the clinical
study. All subjects should indicate whether or not they want to
participate. |
|
| E.4 | Principal exclusion criteria |
• A DSM-IV axis I diagnosis other than schizophrenia that has been the
focus of treatment or cause of disability in the last 6 months. For
example, a major depressive episode that required treatment.
• A DSM-IV diagnosis of substance dependence within 6 months prior to
screening evaluation (nicotine and caffeine dependence are not
exclusionary); patients with a positive urine drug screen at screening may
be included provided use does not lead to a DSM-IV diagnosis of
substance dependence, and investigators should instruct them to abstain
from alcohol and illegal drugs within 3 days prior to Day –1 and at any
time during the study).
• Any clinically relevant medical condition that could potentially alter the
absorption, metabolism, or excretion of the study medication, such as
Crohn’s disease, liver disease, or renal disease.
• Relevant history of any significant and/or unstable cardiovascular,
respiratory, neurological (including seizures) or significant
cerebrovascular, renal, hepatic, endocrine, or immunologic diseases.
• History of neuroleptic malignant syndrome.
• A history of diabetes or currently receiving a glucose lowering agent or
treatment for diabetes.
• Subjects suffering from glaucoma.
• Other significant and/or unstable systemic illnesses.
• Allergy or hypersensitivity to any known antipsychotic compounds.
• Inability to swallow the study medication whole with the aid of water
(subjects may not chew, divide, dissolve, or crush the study medication,
as this may affect the release profile).
•Patients who have never been treated with antipsychotics
• Previous history of lack of response to antipsychotic therapy, including
olanzapine, when acutely psychotic (lack of response is defined as the
subject having had [at least twice] a documented medical history of no
clinical response, despite adequate doses and durations of treatment, or
the inability to tolerate doses in the indicated dosage range).
• Previous use of clozapine for the indications of treatment resistance or
reduction of suicidal risk.
• Exposure to an experimental drug or experimental medical device within
90 days before screening.
• Significant risk of suicidal or violent behavior.
• Female subjects who are pregnant or breastfeeding.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
concentrations more than 2 times the upper limit of normal at screening.
• Other biochemistry, hematology, or urinalysis results that are not within
the laboratory’s reference range, and that are deemed by the investigator
to be clinically significant.
• Clinically significant abnormal observations in Vital Signs. If vital sign
values significantly lie outside the normal ranges at screening, agreement
with the J&J PRD Safety Physician must be obtained prior to inclusion
of the subject.
• Clinically significant abnormal observations in ECG defined as:
– A confirmed screening visit QTcB interval ≥470 msec.
– A history of additional risk factors for torsades des pointes (e.g. heart
failure, hypokalemia, family history of Long QT Syndrome).
– The use of concomitant medications that prolong the QT/QTc interval.
• Use of weight loss drugs such as orlistat, sibutramine or rimonabant.
• Use of Chantix® (varenicline)
• Injection of a depot antipsychotic within 120 days before screening, or
use of paliperidone palmitate within 10 months before screening.
• Use of monoamine oxidase inhibitors within 4 weeks or fluoxetine
within 5 weeks before screening. Use of all other antidepressants within
2 weeks before screening.
• Use of mood stabilizers (e.g., anticonvulsants and/or lithium) within
2 weeks before baseline.
• Received electroconvulsive therapy within 3 months before screening.
• Have been involuntarily committed to psychiatric hospitalization.
• 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, persons with direct
involvement in the proposed study or other studies under the direction of
that investigator or study center, or family members of the employees or
the investigator. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy will be based on the change from baseline of the total PANSS score of three fixed doses of JNJ 37822681 compared with placebo after 6 weeks’ treatment.
Other efficacy criteria include the PANSS subscales, the CGI-S of illness, the SWN compared with placebo at 6 weeks, and compared to olanzapine at 12 weeks. Assessment of the acute response to JNJ 37822681 relative to placebo will be assessed using the changes from baseline in the NOSIE in the first 2 weeks while subjects are hospitalized.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 21 |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 9 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 9 |
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