A Pharmacokinetics Study to Evaluate Safety and Tolerability of JNJ-37822681 in Participants With Stable Schizophrenia

NCT01812642 | Completed Phase 2

• 3 other identifiers: CR0148182007-007669-2037822681SCH2003
• Study Type: interventional
• Target: 33
• Locations: 5 countries
• Sites: 6

Brief Summary

The purpose of this study is to evaluate safety, tolerability and pharmacokinetics (explores what the body does to the drug) of JNJ-37822681 in participants with stable schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self).

Conditions

Schizophrenia

Keywords

Schizophrenia; JNJ-37822681; Placebo

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Day 14

  The AIMS rates the severity of involuntary movements from 0 (none) to 4 (severe), including facial and oral movements, extremity movements, trunk movements, global and judgments, and 2 additional items concerning dental status (yes/no). A total score (ranging from 0 to 28) will be calculated as the sum of items 1 to 7.

  Baseline and Day 14

• Barnes Akathisia Rating Scale (BARS) Score

  The BARS includes an objective rating, 2 subjective ratings of symptoms of akathisia (awareness of restlessness and reported distress related to restlessness: range 0 to 3), and a global clinical rating of akathisia, ranging from 0 (absent) to 5 (severe). The global rating score, that is scored separately, is the most relevant measure of severity of akathisia. Higher scores denote worsening akathisia.

  Day 14

• Change From Baseline in Simpson Angus Rating Scale (SAS) Score

  The SAS rates 10 items from 0 (normal) to 4 (extreme), including gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head rotation, Glabellar tap, tremor and salivation. The SAS global score is the average score (total sum of items score divided by the number of items) and ranges between 0 and 4, where the higher score denotes more severe condition of extra pyramidal symptoms.

  Baseline and Day 14

Secondary Outcomes (8)

• Maximum Concentration (Cmax)

  0 hour (Predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hour post administration of JNJ-37822681 on Day 1 and Day 14

• Concentration at Predose(Cpredose)

  0 hour (Predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hour post administration of JNJ-37822681 on Day 1 and Day 14

• Average Concentration (Cavg)

  0 hour (Predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hour post administration of JNJ-37822681 on Day 1 and Day 14

• Time to Reach Maximum Concentration(tmax)

  0 hour (Predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hour post administration of JNJ-37822681 on Day 1 and Day 14

• Area Under the Plasma Concentration-Time Curve From 0 to 12 or 24 Hours Post Dosing (AUC 0-12h/24h)

  0 hour (Predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hour post administration of JNJ-37822681 on Day 1 and Day 14

Study Arms (2)

JNJ-37822681 10 milligram

EXPERIMENTAL

JNJ-37822681 oral capsule will be administered at a starting dose of 10 milligram (mg) twice daily for the first 3 days and thereafter dose will be titrated from Day 3 to Day 10 up to 80 mg per day and will be continued at same dose up to Day 14.

Drug: JNJ-37822681

JNJ-37822681 20 milligram and placebo

EXPERIMENTAL

JNJ-37822681 oral capsule will be administered at a starting dose of 20 mg once daily for the first 3 days and thereafter dose will be titrated from Day 3 to Day 10 up to 80 mg per day and will be continued at same dose up to Day 14. Matching Placebo will be administered orally in the evening for 14 days (12 hour post JNJ-37822681 administration).

Drug: JNJ-37822681; Other: Placebo

Interventions

JNJ-37822681 DRUG

JNJ-37822681 oral capsule will be administered at a starting dose of either 20 mg (once daily) or 10 milligram (twice daily) for 14 days.

JNJ-37822681 10 milligram; JNJ-37822681 20 milligram and placebo

Placebo OTHER

Matching Placebo will be administered orally, once daily in the evening (12 hour after JNJ-37822681 20 mg administration) for 14 days.

JNJ-37822681 20 milligram and placebo

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Have schizophrenia diagnosis by Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)
• known history of schizophrenia of at least 12 months by the referring psychiatrist
• Positive and Negative Syndrome Scale score at Screening less than 70
• Body Mass Index (BMI) between 18 and 35 kilogram divided by square meter inclusive (BMI =weight per square height)
• Female participants must meet any one of the following: postmenopausal (amenorrhea for at least 12 months and Follicle Stimulating Hormone levels of greater than 40 milli-international unit (MIU ) per milliliter at Screening), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation or otherwise be incapable of pregnancy)

You may not qualify if:

• Any medical condition that could potentially alter the absorption, metabolism or excretion of the study medication, such as Crohn's (serious inflammation of any part of the gastrointestinal tract) 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
• Female participants of childbearing potential
• Significant risk of suicidal or violent behavior

Sponsors & Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: lead

Study Sites (6)

Unknown Facility

Antwerp, Belgium

Location

Unknown Facility

Berlin, Germany

Location

Unknown Facility

Neuss, Germany

Location

Unknown Facility

Nizny Novgorod, Russia

Location

Unknown Facility

Bratislava, Slovakia

Location

Unknown Facility

Stockholm, Sweden

Location

Related Links

• A Double-Blind, Multiple Dose Titration Study to Investigate the Safety, Tolerability and Pharmacokinetics of Once Daily and Twice Daily Doses of JNJ-37822681 in Male and Female Patients With Stable Schizophrenia

MeSH Terms

Conditions

Schizophrenia

Interventions

N-(1-(3,4-difluorobenzyl)piperidin-4-yl)-6-(trifluoromethyl)pyridazin-3-amine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C Clinical Trial

  Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2013
• First Posted: March 18, 2013
• Study Start: July 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: March 18, 2014

Record last verified: 2014-03

Locations

SL (1); BE (1); DE (2); RU (1); SE (1)