An Efficacy and Safety Study of 3 Fixed Doses of JNJ-37822681 in Participants With Schizophrenia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00728195
First received: July 31, 2008
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to evaluate the efficacy and safety of 3 fixed doses of JNJ-37822681 compared with placebo (an inactive substance that is compared with a drug to test if the drug has a real effect in a clinical trial) after 6 weeks treatment and olanzapine after 12 weeks treatment in participants with 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
Drug: Olanzapine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of 3 Fixed Doses of JNJ-37822681 Administered Twice Daily in Subjects With 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 Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent) to 7 (extreme). The total score ranges from 30 to 210 and higher score indicates greater severity.


Secondary Outcome Measures:
  • Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores at Week 6 and 12 [ Time Frame: Baseline, Week 6 and 12 ] [ Designated as safety issue: No ]
    The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent) to 7 (extreme). Positive subscale score ranges from 7 (absent) to 49 (extreme psychopathology), negative subscale score ranges from 7 (absent) to 49 (extreme psychopathology) and general psychopathology subscale score ranges from 16 (absent) to 112 (extreme psychopathology).

  • Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 6 and 12 [ Time Frame: Baseline, Week 6 and 12 ] [ Designated as safety issue: No ]
    The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). Positive symptoms subscale consists of 8 items with total score range of 8-56; negative symptoms subscale and disorganized thoughts subscale, each consists of 7 items with total score range of 7-49 and uncontrolled hostility/excitement (UHE) subscale and anxiety/depression subscale, each consists of 4 items with total score range of 4-28. Higher score indicates greater severity.

  • Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 6 and 12 [ Time Frame: Baseline, Week 6 and 12 ] [ Designated as safety issue: No ]
    The CGI-S rating scale assesses the severity of a participant's overall clinical condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe).

  • Change From Baseline in Subjective Well-Being on Neuroleptics (SWN) Total Score at Week 6 and 12 [ Time Frame: Baseline, Week 6 and 12 ] [ Designated as safety issue: No ]
    The SWN is a participant self rated scale to evaluate the participant's feelings during the past 7 days on a form with 20 statements, subsequently divided into 5 subscales: mental-functioning, self-control, emotional regulation, physical functioning and social integration. Each item is scored between 1 (not at all) and 6 (very much). Total score ranges from 20-120 with higher scores indicating higher subjective well-being.

  • Change From Baseline in Nurses' Observation Scale for Inpatient Evaluation (NOSIE) Total Score at Week 2 [ Time Frame: Baseline and Week 2 ] [ Designated as safety issue: No ]
    The NOSIE comprises 30 items which form 6 scales: social competence, social interest, personal neatness, irritability, manifest psychosis and retardation and is completed by a suitably trained and experienced member of the nursing staff. Each item is scored from 0 (never) to 4 (always). It was assessed only at 2 weeks when the participants were hospitalized. Total score ranges from 0 to 120, with lower score indicating better results.

  • Change From Baseline in Plasma Markers Level for Lipid and Glucose Metabolism at Week 6 and 12 [ Time Frame: Baseline, Week 6 and 12 ] [ Designated as safety issue: Yes ]
    Change from baseline in the level of plasma (liquid part of blood where cells float) markers for lipid (fat) and glucose (type of sugar found in the blood) metabolism (process of breaking down substances in the cells to obtain energy) is calculated. Markers for lipid metabolism include fasting total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), triglycerides and free fatty acids. Fasting glucose level is used as marker for glucose metabolism.

  • Change From Baseline in Free Fatty Acids Level at Week 6 and 12 [ Time Frame: Baseline, Week 6 and 12 ] [ Designated as safety issue: Yes ]
    Change from baseline in the level of free fatty acids (plasma marker for lipid metabolism) is calculated.

  • Change From Baseline in Insulin Level at Week 6 and 12 [ Time Frame: Baseline, Week 6 and 12 ] [ Designated as safety issue: Yes ]
    Change from baseline in the level of insulin (the hormone that controls blood sugar levels) as plasma marker for glucose metabolism is calculated.

  • Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Week 6 and 12 [ Time Frame: Baseline, Week 6 and 12 ] [ Designated as safety issue: Yes ]
    Change from baseline in the level of glycosylated hemoglobin (substance that carries oxygen and gives blood its red color) as plasma marker for glucose metabolism is calculated.

  • Change From Baseline in Body Mass Index (BMI) at Week 6 and 12 [ Time Frame: Baseline, Week 6 and 12 ] [ Designated as safety issue: Yes ]
    The BMI is calculated by dividing the weight (in kilogram) by square of height (in meters).

  • Change From Baseline in Body Weight at Week 6 and 12 [ Time Frame: Baseline, Week 6 and 12 ] [ Designated as safety issue: Yes ]

Enrollment: 498
Study Start Date: November 2008
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo First, Then Olanzapine
Participants will receive 2 matching placebo capsules orally twice daily for 6 consecutive weeks, then 2 matching placebo capsules orally in the morning and olanzapine 10 milligram (mg) capsule along with matching placebo capsule orally in the evening for next 1 week, then 2 matching placebo capsules orally in the morning and olanzapine 10 mg capsule along with olanzapine 5 mg capsule orally in the evening for next 5 weeks.
Drug: Olanzapine
Participants will receive olanzapine 10 mg capsule alone or in combination with olanzapine 5 mg capsule orally for 6 or 12 weeks.
Drug: Placebo
Participants will receive matching placebo capsules orally for 12 weeks.
Experimental: JNJ-37822681 10 mg
Participants will receive 1 matching placebo capsule along with JNJ-37822681 10 mg capsule orally twice a day for 12 consecutive weeks.
Drug: JNJ-37822681
Participants will receive JNJ-37822681 capsule 10 mg orally twice a day for 12 consecutive weeks.
Drug: Placebo
Participants will receive matching placebo capsules orally for 12 weeks.
Experimental: JNJ-37822681 20 mg
Participants will receive 1 matching placebo capsule along with JNJ-37822681 20 mg capsule orally twice a day for 12 consecutive weeks.
Drug: JNJ-37822681
Participants will receive JNJ-37822681 capsule 20 mg orally twice a day for 12 consecutive weeks.
Drug: Placebo
Participants will receive matching placebo capsules orally for 12 weeks.
Experimental: JNJ-37822681 30 mg
Participants will receive JNJ-37822681 30 mg (one 10 mg capsule along with JNJ-37822681 20 mg capsule) orally twice a day for 12 consecutive weeks.
Drug: JNJ-37822681
Participants will receive JNJ-37822681 capsule 30 mg orally twice a day for 12 consecutive weeks.
Active Comparator: Olanzapine
Participants will receive 2 matching placebo capsules orally in the morning and olanzapine 10 mg capsule along with matching placebo capsule orally in the evening for 1 week, then 2 matching placebo capsules orally in the morning and olanzapine 10 mg capsule along with olanzapine 5 mg capsule orally in the evening for next 11 consecutive weeks.
Drug: Olanzapine
Participants will receive olanzapine 10 mg capsule alone or in combination with olanzapine 5 mg capsule orally for 6 or 12 weeks.
Drug: Placebo
Participants will receive matching placebo capsules orally for 12 weeks.

Detailed Description:

This is a multicenter (when more than one hospital or medical school team work on a medical research study), double-blind (neither the participant nor the physician know the study medication drug name), randomized (study drug assigned by chance), placebo- and active-controlled, parallel-group (a clinical trial comparing the response in two or more groups of participants receiving different treatments), dose-response study in participants with schizophrenia. The total study duration will not exceed 16 weeks for each participant and will include following visits: screening, baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 11 and 13 (end of treatment or early withdrawal), and a post-study safety visit (1 week after final dose of study drug). All participants will be hospitalized during the first 2 weeks of treatment for detailed follow-up of safety and disease status. Following a screening period, participants will be randomly assigned to one of 5 treatment groups to receive oral doses of JNJ-37822681 (10, 20 or 30 milligram [mg] twice a day) for 12 weeks, olanzapine 15 mg daily for 12 weeks, or placebo for 6 weeks followed by olanzapine 15 mg daily for the remaining 6 weeks. Olanzapine will be initiated at 10 mg daily for 1 week and then increased to 15 mg daily for the remainder of the treatment period. Efficacy will primarily be evaluated by Positive And Negative Syndrome Scale (PANSS). Participants' safety will also be monitored at each visit.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have been diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) (295.10, 295.20, 295.30, 295.60, 295.90) at least 1 year prior to screening
  • Participants must be experiencing an acute (a quick and severe form of illness in its early stage) exacerbation of less than 6 months duration, with a Positive and Negative Syndrome Scale (PANSS) total score at screening between 70 and 120 inclusive and at baseline of between 60 and 120 inclusive
  • Women of child bearing potential must have a negative urine pregnancy test at screening and baseline before receiving the study drug
  • Participants must agree to voluntary hospitalization for a minimum of 14 days
  • BMI (Body Mass Index) maximum 40 kilogram per meter square (kg/m^2), inclusive (BMI=weight/height^2)

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
  • Any clinically relevant medical condition that could potentially alter the absorption (the way a drug or other substance enters the body), metabolism, or excretion (the way that substances leave the body) of the study medication, such as Crohn's disease (serious inflammation of any part of the gastrointestinal tract), liver disease, or renal (pertaining to the kidneys) disease
  • Relevant history of any significant and/or unstable cardiovascular (pertaining to the heart and blood vessels), respiratory, neurological (including seizures) or significant cerebrovascular (pertaining to brain and blood vessels), renal, hepatic, endocrine (pertaining to the glands that make hormones), or immunologic diseases
  • History of neuroleptic malignant syndrome (high fever, rigid muscles, shaking, confusion, sweating more than usual, increased heart rate or blood pressure, or muscle pain or weakness)
  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: NCT00728195

  Show 48 Study Locations
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 by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00728195     History of Changes
Other Study ID Numbers: CR014737, 37822681SCH2002, 2007-007083-22
Study First Received: July 31, 2008
Last Updated: March 25, 2014
Health Authority: Lithuania: Bioethics Committee
Ukraine: State Pharmacological Center - Ministry of Health

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

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Olanzapine
Antiemetics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 23, 2014