Back to resultsAn Efficacy and Safety Study of 3 Fixed Doses of JNJ-37822681 in Participants With Schizophrenia
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
JNJ-37822681
JNJ-37822681
JNJ-37822681
Olanzapine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Central Nervous System, JNJ-37822681
Eligibility 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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Active Comparator
Arm Label
Placebo First, Then Olanzapine
JNJ-37822681 10 mg
JNJ-37822681 20 mg
JNJ-37822681 30 mg
Olanzapine
Arm Description
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.
Participants will receive 1 matching placebo capsule along with JNJ-37822681 10 mg capsule orally twice a day for 12 consecutive weeks.
Participants will receive 1 matching placebo capsule along with JNJ-37822681 20 mg capsule orally twice a day for 12 consecutive weeks.
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.
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.
Outcomes
Primary Outcome Measures
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6
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
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
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
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
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
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
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
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
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
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
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
Full Information
NCT ID
NCT00728195
First Posted
July 31, 2008
Last Updated
March 25, 2014
Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
1. Study Identification
Unique Protocol Identification Number
NCT00728195
Brief Title
An Efficacy and Safety Study of 3 Fixed Doses of JNJ-37822681 in Participants With Schizophrenia
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
February 2010 (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
Yes
5. Study Description
Brief Summary
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia, Central Nervous System, JNJ-37822681
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
498 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo First, Then Olanzapine
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
JNJ-37822681 10 mg
Arm Type
Experimental
Arm Description
Participants will receive 1 matching placebo capsule along with JNJ-37822681 10 mg capsule orally twice a day for 12 consecutive weeks.
Arm Title
JNJ-37822681 20 mg
Arm Type
Experimental
Arm Description
Participants will receive 1 matching placebo capsule along with JNJ-37822681 20 mg capsule orally twice a day for 12 consecutive weeks.
Arm Title
JNJ-37822681 30 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Olanzapine
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
JNJ-37822681
Intervention Description
Participants will receive JNJ-37822681 capsule 10 mg orally twice a day for 12 consecutive weeks.
Intervention Type
Drug
Intervention Name(s)
JNJ-37822681
Intervention Description
Participants will receive JNJ-37822681 capsule 20 mg orally twice a day for 12 consecutive weeks.
Intervention Type
Drug
Intervention Name(s)
JNJ-37822681
Intervention Description
Participants will receive JNJ-37822681 capsule 30 mg orally twice a day for 12 consecutive weeks.
Intervention Type
Drug
Intervention Name(s)
Olanzapine
Intervention Description
Participants will receive olanzapine 10 mg capsule alone or in combination with olanzapine 5 mg capsule orally for 6 or 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive matching placebo capsules orally for 12 weeks.
Primary Outcome Measure Information:
Title
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6
Description
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.
Time Frame
Baseline and Week 6
Secondary Outcome Measure Information:
Title
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores at Week 6 and 12
Description
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).
Time Frame
Baseline, Week 6 and 12
Title
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 6 and 12
Description
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.
Time Frame
Baseline, Week 6 and 12
Title
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 6 and 12
Description
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).
Time Frame
Baseline, Week 6 and 12
Title
Change From Baseline in Subjective Well-Being on Neuroleptics (SWN) Total Score at Week 6 and 12
Description
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.
Time Frame
Baseline, Week 6 and 12
Title
Change From Baseline in Nurses' Observation Scale for Inpatient Evaluation (NOSIE) Total Score at Week 2
Description
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.
Time Frame
Baseline and Week 2
Title
Change From Baseline in Plasma Markers Level for Lipid and Glucose Metabolism at Week 6 and 12
Description
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.
Time Frame
Baseline, Week 6 and 12
Title
Change From Baseline in Free Fatty Acids Level at Week 6 and 12
Description
Change from baseline in the level of free fatty acids (plasma marker for lipid metabolism) is calculated.
Time Frame
Baseline, Week 6 and 12
Title
Change From Baseline in Insulin Level at Week 6 and 12
Description
Change from baseline in the level of insulin (the hormone that controls blood sugar levels) as plasma marker for glucose metabolism is calculated.
Time Frame
Baseline, Week 6 and 12
Title
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Level at Week 6 and 12
Description
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.
Time Frame
Baseline, Week 6 and 12
Title
Change From Baseline in Body Mass Index (BMI) at Week 6 and 12
Description
The BMI is calculated by dividing the weight (in kilogram) by square of height (in meters).
Time Frame
Baseline, Week 6 and 12
Title
Change From Baseline in Body Weight at Week 6 and 12
Time Frame
Baseline, Week 6 and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnson & Johnson Pharmaceutical Research & Development, L.L.C Clinical Trial
Organizational Affiliation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Official's Role
Study Director
Facility Information:
City
Bourgas
Country
Bulgaria
City
Pazardjik
Country
Bulgaria
City
Radnevo
Country
Bulgaria
City
Rousse
Country
Bulgaria
City
Sofia N/A
Country
Bulgaria
City
Tallinn
Country
Estonia
City
Tartu N/A
Country
Estonia
City
Gwangju
Country
Korea, Republic of
City
Gyeongsangnam-Do
Country
Korea, Republic of
City
Incheon
Country
Korea, Republic of
City
Seoul
Country
Korea, Republic of
City
Kaunas
Country
Lithuania
City
Vilnius
Country
Lithuania
City
Johor Bahru
Country
Malaysia
City
Kuala Lumpur
Country
Malaysia
City
Kuching
Country
Malaysia
City
Arad
Country
Romania
City
Brasov
Country
Romania
City
Bucharest
Country
Romania
City
Bucuresti
Country
Romania
City
Jebel
Country
Romania
City
Oradea
Country
Romania
City
Sibiu
Country
Romania
City
Tg Mures
Country
Romania
City
Ekaterinburg Na
Country
Russian Federation
City
Moscow N/A
Country
Russian Federation
City
Moscow Russia
Country
Russian Federation
City
N Novgorod Na
Country
Russian Federation
City
Samara
Country
Russian Federation
City
Saratov
Country
Russian Federation
City
St Petersburg N/A
Country
Russian Federation
City
St Petersburg
Country
Russian Federation
City
St-Petersburg
Country
Russian Federation
City
Tomsk Na
Country
Russian Federation
City
Yaroslavl
Country
Russian Federation
City
Cape Town
Country
South Africa
City
Centurion Gauteng
Country
South Africa
City
Pretoria
Country
South Africa
City
Hua Lian
Country
Taiwan
City
Kaohsiung
Country
Taiwan
City
Taipei
Country
Taiwan
City
Dnipropetrovsk
Country
Ukraine
City
Donetsk
Country
Ukraine
City
Kharkov
Country
Ukraine
City
Kherson
Country
Ukraine
City
Kiev
Country
Ukraine
City
Odessa
Country
Ukraine
City
Simferopol
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
22995972
Citation
Anghelescu IG, Janssens L, Kent J, de Boer P, Tritsmans L, Daly EJ, van Nueten L, Schmidt ME. Does early improvement predict response to the fast-dissociating D(2) receptor antagonist JNJ-37822681 in patients with acute schizophrenia? Eur Neuropsychopharmacol. 2013 Sep;23(9):1043-50. doi: 10.1016/j.euroneuro.2012.08.017. Epub 2012 Sep 18.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=778&filename=CR014737_CSR.pdf
Description
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
Learn more about this trial
An Efficacy and Safety Study of 3 Fixed Doses of JNJ-37822681 in Participants With Schizophrenia
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