| Eligibility |
Inclusion Criteria:
1. Right-handed participants between the ages of 18 and 60 years, inclusive, who are
currently in a euthymic mood state defined as =8 on the Hamilton Rating Scale for
Depression (HAM-D) and Young Mania Rating Scale (YMRS).
2. The participant has a resting pulse =51 bpm and =100 bpm.
3. The subject has a resting systolic blood pressure =91 mmHg and =140 mmHg and a resting
diastolic blood pressure =51 mmHg and =90 mmHg at the Screening Visit. An out-of-range
resting systolic blood pressure may be repeated if a medically valid reason is
present, for example, the subject suffers from white-coat hypertension or experienced
stress (e.g. late arrival).The medically valid reason must be documented and signed by
the investigator.
4. The subject has clinical laboratory test values within the reference ranges based on
the blood and urine samples taken at the Screening Visit. Borderline value parameters
may be accepted if they are, in the opinion of the investigator, clinically
insignificant.
5. Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the trial.
6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other trial procedures.
7. Ability to understand written and verbal instructions in English.
8. Women of child bearing potential must have a negative pregnancy test at screening and
at baseline visits and must agree to use a medically accepted method of contraception
throughout the study.
Exclusion Criteria:
1. Evidence or history of clinically significant haematological, renal, endocrine,
pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, or allergic disease
(including drug allergies, but excluding untreated, asymptomatic, seasonal allergies
at time of dosing), and any primary psychiatric diagnosis other than bipolar disorder.
2. Participants who have used or plan to use during the conduct of the study:
1. Fluoxetine within 5 weeks prior to the baseline visit or during the study
2. Monoamine oxidase inhibitors within 3 weeks of the baseline visit or during the
study
3. Other prescription medication within 7 days prior to the baseline visit or within
or 5 half-lives (whichever is longer) with the exception of the following which
are allowed:
i. For the bipolar disorder group, prescribed psychotropic medications as long as they
are not included in the list of CYP2D6 and CYP2C19 medications listed in exclusion's 3
and 4 below.
ii. Limited use (not more than 3 days per week) medications (non CYP2D6 or CYP2C19
substrates) such as prn treatments for asthma or acute migraine.
iii. Women who are taking hormone replacement therapy or hormonal contraception must
be on a stable regimen for 30 days prior to screening and remain on that regimen
throughout the study
iv. Paracetamol may be used at doses of 1 g/day
Herbal supplements must be discontinued 28 days prior to the first dose of study
medications. At the discretion of the investigator a shorter drug free or
discontinuation period may be acceptable depending on the precise drugs/supplements
taken.
3. As JNJ-18038683 is a strong inhibitor of cytochrome P450 2D6, use of the following
CYP2D6 substrates will be an exclusion: carvedilol, S-metoprolol, propafenone,
timolol, amitriptyline, clomipramine, desipramine, fluoxetine, imipramine, paroxetine,
venlafaxine, haloperidol, perphenazine, risperidone, thioridazine, zuclopenthixol,
alprenolol, amphetamine, aripiprazole, atomoxetine, bufuralol, chlorpheniramine,
chlorpromazine, clonidine, codeine, debrisoquine, dexflenfluramine, dextromethorphan,
donepezil, duloxetine, encainide, flecainide, fluvoxamine, lidocaine, metoclopramide,
methoxyamphetamine, mexilletine, minaprine, nebivolol, nortriptyline, ondansetron,
oxycodone, perhexiline, phenacetin, phenformin, promethazine, propafenone,
propranolol, sparteine, tamoxifen, tramadol, venlafaxine. Participants planning to use
these medications after their participation in the study must commit to a two-week
washout period at the end of the study before commencing these medications.
4. As JNJ-18038683 is a moderate inhibitor of cytochrome P450 2C19, use of the following
CYP2C19 substrates will be an exclusion: Proton pump inhibitors, phenytoin,
phenobarbitone, diazepam, Norphenytoin, S-mephenytoin, phenobarbitone, amitriptyline,
carisoprodol, citalopram, chloramphenicol, clomipramine, clopidogrel,
cyclophosphamide, hexobarbital, imipramine, indomethacin, labetalol, R-mephobarbital,
moclobemide, nelfinavir, nilutamide, primidone, progesterone, proguanil, propranolol,
teniposide, warfarin, voriconazole. Participants planning to use these medications
after their participation in the study must commit to a two-week washout period at the
end of the study before commencing these medications.
5. Currently taking medications with significant 5HT7 antagonist properties (eg
lurasidone, vortioxetine)
6. Treatment with another experimental medicine drug within the 3 months preceding the
first dose of study medication, over the course of the study, and two weeks after
discontinuing study medications
7. History of sensitivity to JNJ-18038683 or other medications with 5HT7 antagonist
properties.
8. History of febrile illness within 5 days prior to the first dose.
9. Any condition possibly affecting drug absorption (eg, gastrectomy).
10. 12-lead ECG considered abnormal by a clinician
11. A positive urine drug screen on or after the screening visit during their active
involvement in the study for opiates, methadone, cocaine, amphetamines (including
MDMA), barbiturates, benzodiazepines and cannabinoids.
12. Unwilling or unable to comply with the Lifestyle guidelines.
13. Participants who, in the opinion of the investigator, have any medical or
psychological condition or social circumstances which would impair their ability to
participate reliably in the study, or who may increase the risk to themselves or
others by participating.
14. Diagnosis of alcohol or drug dependence in the year prior to recruitment or diagnosis
of harmful use of alcohol or drugs within the previous 6 months.
15. Female participants of child bearing potential who are not using adequate
contraception as specified in above criteria for inclusion.
16. Female participants that are currently pregnant or are breast feeding.
17. A history of moderate to severe head injury or neurological conditions that may impair
cognitive performance
18. Ineligibility to undergo MRI imaging, for example the presence of a cardiac pacemaker
or other electronic device or ferromagnetic metal foreign bodies as assessed by a
standard pre-MRI questionnaire.
19. Participant weight in excess of 126kg or physical dimensions such that the participant
may not fit in the MRI scanner.
20. A history of claustrophobia or participant feels unable to lie in a MRI scanner for a
period of around one hour.
Additional exclusion criteria for participants with bipolar disorder
1. Significant change in dose or type of prescribed psychotropic medications in the month
prior to the Screening visit or likely change during the study.
Additional exclusion criteria for healthy participants
1. A personal history of any significant psychiatric disorder including a history of
suicide attempts or significant suicidal ideation or a family history of severe mental
illness (such as psychosis, bipolar disorder or schizophrenia).
|
