Clinical trial NCT00686699: Study of Preladenant for the Treatment of Antipsychotic Induced Movement Disorders in Participants With Schizophrenia (Study P04628)
Official title: A Phase 2a, Multiple Dose, Placebo Controlled, Randomized, Two Way Crossover Study to Assess the Efficacy of SCH 420814 in Reducing Anti Psychotic-Induced Extra Pyramidal Symptoms Among Subjects With Schizophrenia and Schizoaffective Disorders
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Akathisia, Drug-Induced
Dyskinesia, Drug-Induced
Parkinsonian Disorders
Keywords: Anti-Dyskinesia Agents
Antipsychotic Agents
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-05-30
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study was designed to determine if preladenant (SCH 420814, MK-3814) can reduce drug-induced involuntary movements in participants with schizophrenia or schizoaffective disorder. Participants were to be evaluated for two 14-day treatment periods with a 3-week washout period between treatment periods. The primary outcome measure, Extrapyramidal Symptom Rating Score (ESRS), was to be evaluated frequently during the treatment periods.


Eligibility criteria: Inclusion Criteria:

* Males or females \>=18 and \<=65 years old with a body mass index of 17-31 kg/m\^2.
* Diagnosed with Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (DSM-IV) criteria for schizophrenia/schizoaffective (depressive type) disorder with antipsychotic-induced extrapyramidal symptoms (parkinsonism, akathisia, dystonia, or tardive dyskinesia \[TD\]) based on the following ESRS criteria:

  * parkinsonism, dystonia, or TD - ESRS score \>=2 on 2 items or \>=3 on one item,
  * akathisia - ESRS score \>=3 on two items,
* Has total ESRS score \>8.
* Must be receiving neuroleptics at a stable dosage for at least 7 days prior to enrollment.
* Clinical laboratory tests, physical exam, and electrocardiogram must be within normal limits or clinically acceptable to the investigator/sponsor (except signs and symptoms of Schizophrenia/Schizoaffective disorder).
* Liver function tests must be within normal limits at screening.
* Participant screening for drugs with a high potential for abuse must be negative.
* Must be free of any clinically significant disease other than schizophrenia/schizoaffective disorder that would interfere with the study evaluations or procedures.
* Must have a level of understanding sufficient to communicate with research staff, cooperate with all protocol required tests and examinations, and be able to adhere to protocol restrictions and schedules.
* Must be able to understand the nature of the study and must be willing to sign an informed consent (required for each patient or the patient's authorized legal representative) prior to study enrollment.
* Females must have a follicle stimulating hormone (FSH) \>=40 lU/L and be greater than 12 months since last menses or surgically sterilized.

Exclusion Criteria:

* Has a history of clinically significant local or systemic infectious disease within 4 weeks prior to initial treatment administration, clinically significant food or drug allergy, seizures, alcohol/drug dependence, previous neurosurgery, or coronary artery disease (including myocardial infarction \[MI\], cerebrovascular disease \[stroke, transient ischemic attack (TIA)\], or peripheral arterial disease).
* Has participated in a clinical trial of an investigational drug within 60 days or donated blood within the preceding 90 days prior to the start of the study.
* Has circulating human immunodeficiency virus (HIV), hepatitis C antibodies, or hepatitis B surface antigen.
* Is allergic to preladenant (SCH 420814, MK-3814) or any excipients in preladenant capsules (citric acid, lactose monohydrate, croscarmellose sodium, magnesium stearate \[nonbovine, vegetable grade\], Food, Drug, and Cosmetic \[FD\&C\] blue, titanium dioxide, gelatin-national formulary \[NF\]).
* Females who are not surgically sterilized or postmenopausal.
* Males who are sexually active and who do not agree to use a barrier method of birth control during the study.
* Has severe/uncontrolled hypertension. (Participants with hypertension well controlled on a stable dose of standard anti-hypertensive medication for at least 4 weeks before randomization are eligible.)
* Has atrioventricular (AV) block, sick sinus syndrome, congestive heart failure, or participants with electrocardiograms (ECGs) consistent with ischemic heart disease, or significant Q waves.
* Has 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 or comply with the study procedures or the instructions of the staff or are socially incapable to participate in the study.
* Does not comply with the requirement that participants should not use any drugs (except acetaminophen and other allowed medications) within 2 weeks prior to the study, nor alcohol (wine, beer) within 72 hours prior to drug administration.
* Judged clinically to be at suicidal risk too serious to be included in this study.
* Has received electroconvulsive therapy within 30 days before randomization.
* Is currently taking clozapine.

Primary outcomes:
measure: Lowest Extrapyramidal Symptom Rating Score (ESRS) Total Score Within the 6-hour Evaluation on Day 14 of Each Treatment Period
timeFrame: Up to 6 hours post-dose on Day 14
Secondary outcomes:
measure: Mean ESRS Total Scores Within the 6-hour Evaluation on Day 14 of Each Treatment Period
timeFrame: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
measure: Lowest ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period
timeFrame: Up to 6 hours post-dose on Day 14
measure: Mean ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period
timeFrame: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
measure: Lowest ESRS Part II Subscore: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
timeFrame: Up to 6 hours post-dose on Day 14
measure: Mean ESRS Part II Subscores: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
timeFrame: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
measure: Lowest ESRS Part III Subscore: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
timeFrame: Up to 6 hours post-dose on Day 14
measure: Mean ESRS Part III Subscores: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
timeFrame: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
measure: Lowest ESRS Part IV Subscore: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
timeFrame: Up to 6 hours post-dose on Day 14
measure: Mean ESRS Part IV Subscores: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
timeFrame: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: