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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

JNJ-37822681

Placebo

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, JNJ-37822681, Placebo

Eligibility Criteria

20 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

JNJ-37822681 10 milligram

JNJ-37822681 20 milligram and placebo

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Maximum Concentration (Cmax)

The Cmax is peak plasma concentration, determined by visual inspection of the data.

Concentration at Predose(Cpredose)

Cpredose is predose plasma concentration (intermittent days and predose Day 14).

Average Concentration (Cavg)

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)

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)

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])

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

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

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.

Full Information

NCT ID

NCT01812642

First Posted

March 14, 2013

Last Updated

March 16, 2014

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT01812642

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2014

Overall Recruitment Status

Completed

Study Start Date

July 2008 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

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

4. Oversight

Data Monitoring Committee

No

5. Study Description

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia

Keywords

Schizophrenia, JNJ-37822681, Placebo

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

JNJ-37822681 10 milligram

Arm Type

Experimental

Arm Description

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.

Arm Title

JNJ-37822681 20 milligram and placebo

Arm Type

Experimental

Arm Description

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).

Intervention Type

Drug

Intervention Name(s)

JNJ-37822681

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

Baseline and Day 14

Title

Barnes Akathisia Rating Scale (BARS) Score

Description

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.

Time Frame

Day 14

Title

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

Description

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.

Time Frame

Baseline and Day 14

Secondary Outcome Measure Information:

Title

Maximum Concentration (Cmax)

Description

The Cmax is peak plasma concentration, determined by visual inspection of the data.

Time Frame