| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 Objectives
The primary objective is to investigate the safety and tolerability of JNJ-37822681 administered as qd or bid following a dose titration in male and female patients with stable schizophrenia.
|
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study include:
·To investigate the plasma pharmacokinetic (PK) profile of JNJ-37822681 administered as once daily (qd) or twice daily (bid) in male and female patients with stable schizophrenia;
·To investigate the effect of JNJ-37822681 on plasma prolactin (PRL) levels.
·To investigate the occupancy of striatal dopamine D2 receptors of JNJ-37822681 following multiple dose administration in relation to the plasma pharmacokinetic (PK) profile using [11C]-raclopride PET.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• 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
• Male or female between 20 and 55 years of age, inclusive; subjects who
will have a PET scan will be aged between 20 and 45 years, inclusive.
• Female subjects must meet one of the following:
– postmenopausal (amenorrhoea for at least 12 months and FSH levels
of >40 MIU/mL at screening),
– surgically sterile, (have had a hysterectomy or bilateral oophorectomy,
tubal ligation, or otherwise be incapable of pregnancy)
• Men participating in this study have to use a condom at each sexual
intercourse even when their partner is pregnant. They should not father a
child and not donate sperm during the study and for 3 months after
receiving the last dose of study drug. For men that have been clinically
determined to be vasectomized, this restriction applies for 5 days after
receiving the last dose of study drug. Also their female partner should use
an effective method of contraception above the condom used by the male
study subject. (Effective methods of contraception include prescription
oral contraceptives, contraceptive injections, intrauterine device, doublebarrier
method, contraceptive patch).
• In- or outpatients with schizophrenia stably treated for at least 6 months
with antipsychotic monotherapy (≤ 200mg/d chlorpromazine equivalent
dose) or stable for at least 3 months without drug therapy; patients who
receive a second antipsychotic at doses < recommended for
antipsychotic efficacy may participate provided the second antipsychotic
will be discontinued at least 2 weeks prior to first dose administration.
• PANSS at screening < 70
• DSM-IV criteria for Schizophrenia
• In the opinion of the investigator and in compliance with local
regulations, the subject can be withdrawn from current antipsychotic
medication.
• A known history of schizophrenia of at least 12 months by the referring
psychiatrist.
• Body Mass Index (BMI) between 18 and 35 kg/m2 inclusive (BMI =
weight/height2)
• Willing to be hospitalized during the double-blind treatment period of
the study.
• Willing to adhere to the prohibitions and restrictions specified in this
protocol. |
|
| E.4 | Principal exclusion criteria |
• A DSM-IV axis I diagnosis other than schizophrenia
• 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 drug screen at screening may be
included provided use does not lead to a DSM-IV diagnosis of substance
dependence and patients consent to abstain from alcohol and illegal
drugs within 3 days prior to Day –1 and at any time during the study)
• Any 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, neurologic (including seizures or significant
cerebrovascular), renal, hepatic, endocrine, or immunologic diseases
• History of neuroleptic malignant syndrome (NMS)
• 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)
• Exposure to an experimental drug or experimental medical device within
90 days before screening
• Significant risk of suicidal or violent behavior
• Female subjects of childbearing potential
• Female subjects who are pregnant or breastfeeding
• Alanine aminotransferase or aspartate aminotransferase levels more than
2 times the upper limit of normal at screening or baseline
• 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
• Use of beta-blockers (if used for any indication other than hypertension
and still present at baseline)
• Injection of a depot antipsychotic within 120 days before screening, or
use of paliperidone palmitate within 10 months before screening
• Use of fluoxetine or monoamine oxidase inhibitors within 4 weeks before
screening
• Use of all other antidepressants, anticonvulsants, or lithium within
2 weeks before baseline
• Received electroconvulsive therapy within 3 months before screening
• Have been involuntarily committed to psychiatric hospitalization
• Donation of 1 or more units (approximately 450 mL) of blood or acute
loss of an equivalent amount of blood within 90 days prior to study drug
administration.
• Any condition that, in the opinion of the investigator, would compromise
the well-being of the subject or the study
• 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.
• Additional exclusion criteria for subjects enrolled at the PET centers:
• Any clinically significant MRI abnormalities as determined by a
neuroradiologist, which are relevant for the study.
• Metal implants (pacemakers, joint replacements, etc.), which are
relevant for MRI or PET procedures or data.
• The total effective radiation dose for the subject should not exceed
10 mSv during the time period from 12 months before to 12 months
after the study.
• Use of sertindole and aripiprazole within 4 weeks before screening. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
To evaluate the safety, tolerability, striatal D2 dopamine receptor occupancy and
plasma pharmacokinetics of JNJ-37822681 in patients with schizophrenia in
the predicted clinical dose range. This study will be performed as a dosetitration
study within a single patient rather than a parallel-group study as it
is anticipated that a gradual increase in JNJ-37822681 dose levels (and
plasma concentrations) will be better tolerated in schizophrenic patients who
are washing out from previous antipsychotic medication. |
|
| 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 | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| 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) | 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| multi-center, multiple dose titration study |
|
| 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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 4 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
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