Patients with schizophrenia and schizoaffective disorders experiencing anti-psychotic-induced extra-pyramidal symptoms. MedDRA version: 8.1 Level: LLT Classification code 10039626
Conditions
Interventions
Product Name: SCH 420814
Product Code: SCH 420814
Pharmaceutical Form: Capsule*
CAS Number: 377727-87-2
Other descriptive name: SCH 420814
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
Schering-Plough Research Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Males/Females 18-65 years old with BMI 17-31. 2)Subjects with DSM-IV criteria of schizophrenia and schizoaffective (depressive type) disorder with anti-pyschotic-induced Extrapyramidal Symptoms (EPS), such as parkinsonism and/or akathisia and/or dystonia and/or tardive dyskinesia (TD) based on developed ESRS criteria:a)An ESRS score of 2 on 2 items or a score of 3 or greater on one item is required to establish a presence of parkinsonism; b) An ESRS score of 2 on 2 items or a score of 3 or greater on one item is required to establish a presence of dystonia; c) An ESRS score of 2 on 2 items or a score of 3 or greater on one item is required to establish a presence of TD; d) An ESRS score of 3 or greater on the two items is required to establish a presence of akathisia; e) subjects must have a minimum total score the ESRS of 8. 3)To enter the treatment phase of the study, subjects must be receiving neuroleptics (haloperidol, cyamemazine, tiapride, sulpiride, levomepromazine, perphenazine, perazine, melperone, promethazine, pipameperone, chlorprothixene, chlorpromazine or Risperidone), at a stable dosage for at least 7 days prior to enrollment. Other neuroleptics that have caused ESP may be considered after discussion between sponsor and site. 4)Clinical laboratory tests must be within normal limits or clincally acceptable to the investigator. All subjectsshould have their liver function tests within normal limits on screening. 5)Drug screen for drugs with a high potential for abuse must be negative. 6)Subjects must be free of any clinically significant disease other than schizophrenia and schizoaffective (depressive type) disorder that would interfere with the study evaluation of procedures. 7)Subjects must have a level of understanding sufficient to communicate with the research staff and to cooperate with all tests and examinations required by the protocol and be able to adhere to protocol restrictions and schedules. 8)Subjects must be able to understand the nature of the study and must be willing to sign an informed consent (required for each subject and/or the subject's authorized legal reporesentative) prior to study enrollment. 9)Physical exam must be within normal limits or clinically acceptable to the investigator/sponsor (except signs and symtpoms of of schizophernia and schizoaffective disorder). 10)Females must have a FSH>/=40 IU/L and last menses or surgically sterilized must be greater than 12 months. 11)The electrocardiogram (12-lead recorded at 25 mm/s and reporting ventricular rate and PR, QRS, QT and QTc intervals) must be clinically acceptable. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1)Subjects who have a history of any clinically significant local or systemic infectious disease within 4 weeks prior to initial treatment administration. 2)Subjects who have participated in a clinical trial of an investigational drug within 60 days prior to the start of the study. 3)Subjects who have a clinically significant history of food or drug allergy. 4)Subjects who have donated blood within the preceding 90 days. 5)Subjects with circulating HIV, hepatitis C antibodies, or hepatitis B surface antigen. 6)Subjects who are allergic to SCH 420814 or are allergic to any of the excipients in SCH 420814 capsules (citric acid, lactose monohydrate, croscarmellose sodium, magnesium stearate [nonbovine, vegetable grade], FD&C blue, titanium dioxide, gelatin-NF). 7)Females who are not surgically sterilized or postmenopausal. 8)Male subjects who are sexually active and who do not agree to use a barrier method of birth control during the study an for 30 days after the study. 9)Subjects with severe/uncontrolled hypertension will be excluded. Subjects with hypertension well controlled on a stable dose of standard antihypertensive medication for at least 4 weeks before randomization are eligible. 10)Subjects with history of coronary artery disease including MI, or cerebrovascular disease (stroke, TIA), or peripheral arterial disease. 11)Subjects with atrioventricular (AV) block, sick sinus syndrome, congestive heart failure, or subjects with ECGs consistent with ischemic heart disease, or significant Q waves. 12)Subjects with a history of any of the following: seizures, alcohol/drug dependence, previous neurosurgery. 13)Subjects with DSM-IV criteria of dementia (except due to Schizophrenia and Schizoaffective disorder), or individuals who in the opinion of the investigator are not able to understand and/or comply to the study procedures and/or the instructions of the staff or are socially incapable to participate in the study. Vulnerable subjects (eg, subjects kept in detention) will be excluded from study participation. 14)Individuals who do not comply with the requirement that he or she should not have used any drugs (except acetaminophen and other allowed medications) within two weeks prior to the study nor alcohol or caffeine/xanthine containing products (chocolates, wine, beer) within 72 hours prior to drug administration. Smoking will be allowed during the study and the washout periods to the extent that it does not interfere with the assessments and sample collections. Caffeinated and decaffeinated beverages will be allowed during the study and the washout periods. 15)Subjects who were judged clinically to be at suicidal risk too serious to be included in this study. 16)Subjects who had received electroconvulsive therapy (ECT) within 30 days before randomization. 17)Subjects who are currently taking Clozapine will be excluded from study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess if anti-psychotic-induced extra-pyramidal symptoms can be reduced by SCH 420814 at the dose of 25mg BID.;Secondary Objective: To assess the safety and tolerability of SCH 420814 as an adjunct to anti-psychotic therapy. To document the pharmacokinetics of SCH 420814.;Primary end point(s): The primary efficacy endpoint is the lowest ESRS total score within the 6-hour range on day 14. The secondary efficacy end points include each lowest sub-score within the 6-hour range on day 14, each sub-score at hours 1, 2, 3, 4, 5, 6 on day 14, the total score at hours 1, 2, 3, 4, 5, 6 on day 14, and the time-weighted average total score on day 14. Pharmacokinetic: The derived pharmacokinetic parameters (AUC and Cmax) will be listed and concentration data will be tabulated by each sampling time. Exploratory Analyses: The percent improvement from baseline in ESRS scores on day 14 (ie. 20% improvement, 30% improvement, etc) along with the 95% confidence interval will be summarized by the treatments. A regression type analysis may be carried out to evaluate a possible relationship between the efficacy endpoints and SCH 420814 concentrations / PK parameters. | — |
Countries
Germany
Outcome results
None listed