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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT01812642
First received: March 14, 2013
Last updated: March 16, 2014
Last verified: March 2014
  Purpose

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).


Condition Intervention Phase
Schizophrenia
Drug: JNJ-37822681
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Day 14 [ Time Frame: Baseline and Day 14 ] [ Designated as safety issue: Yes ]
    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.

  • Barnes Akathisia Rating Scale (BARS) Score [ Time Frame: Day 14 ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Simpson Angus Rating Scale (SAS) Score [ Time Frame: Baseline and Day 14 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Maximum Concentration (Cmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The Cmax is peak plasma concentration, determined by visual inspection of the data.

  • Concentration at Predose(Cpredose) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Cpredose is predose plasma concentration (intermittent days and predose Day 14).

  • Average Concentration (Cavg) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The Cavg is average plasma concentration at steady state and it will be calculated as AUC (τ)/τ (where time τ is the dosing interval).

  • Time to Reach Maximum Concentration(tmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The Tmax is time to reach the peak plasma concentration and will be determined by visual inspection of the data.

  • Area Under the Plasma Concentration-Time Curve From 0 to 12 or 24 Hours Post Dosing (AUC 0-12h/24h) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The AUC 0-12h/24h is area under the plasma concentration-time curve from 0 to 12 or from 0 to 24 hours post dosing on Day 1 and Day 14 and will be calculated by trapezoidal summation.

  • Area Under the Plasma Concentration-Time Curve From 0 to Tau Hours Post Dosing (AUC[0-tau]) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The AUC(0-tau) is area under the plasma concentration-time curve from 0 to τ hours post dosing at steady state and it will be calculated by trapezoidal summation (where time τ is the dosing interval).

  • Positive and Negative Syndromes Scale (PANSS) Total Score [ Time Frame: Baseline up to 14 days after last study dose ] [ Designated as safety issue: No ]
    The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening.

  • Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale Score at Day 10 and 14 [ Time Frame: Baseline, Day 10 and 14 ] [ Designated as safety issue: No ]
    The CGI-S rating scale is a 7-point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher scores indicate worsening.


Enrollment: 33
Study Start Date: July 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: JNJ-37822681 10 milligram
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 oral capsule will be administered at a starting dose of either 20 mg (once daily) or 10 milligram (twice daily) for 14 days.
Experimental: JNJ-37822681 20 milligram and placebo
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
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.
Other: Placebo
Matching Placebo will be administered orally, once daily in the evening (12 hour after JNJ-37822681 20 mg administration) for 14 days.

Detailed Description:

This is a double-blind (neither physician nor participant knows the treatment that the participant receives), multi-center (conducted in more than one center), randomized (treatment group assigned by chance), and multiple-dose titration study of JNJ-37822681 in participants with stable schizophrenia. The total study duration will be approximately of 8 weeks per participant, consists of 4 parts: Screening (that is, 21 days before study commences on Day 1); Double-blind treatment (14 days); Follow-up (7 to 14 days after last dose administration). Participants will be randomly assigned to treatment with ascending dose levels of JNJ-37822681 once daily and twice daily. Efficacy will primarily be evaluated by Positive and Negative Syndrome Scale and Clinical Global Impression-Severity scale. Safety will be Barnes Akathisia Rating Scale, Abnormal Involuntary Movement Scale and Simpson Angus Rating Scale. Participants' safety will be monitored throughout the study.

  Eligibility

Ages Eligible for Study:   20 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01812642

Locations
Belgium
Antwerpen, Belgium
Germany
Berlin, Germany
Neuss, Germany
Russian Federation
Nizny Novgorod, Russian Federation
Slovakia
Bratislava, Slovakia
Sweden
Stockholm, Sweden
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L.C Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT01812642     History of Changes
Other Study ID Numbers: CR014818, 2007-007669-20, 37822681SCH2003
Study First Received: March 14, 2013
Last Updated: March 16, 2014
Health Authority: Russia: Ministry of Health of the Russian Federation

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Schizophrenia
JNJ-37822681
Placebo

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on September 18, 2014