Study of Preladenant for the Treatment of Antipsychotic Induced Movement Disorders in Participants With Schizophrenia (Study P04628)

October 10, 2018 updated by: Merck Sharp & Dohme LLC

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Preladenant 25 mg BID→Placebo BID
Participants received one preladenant 25 mg capsule twice daily (BID) for 14 days during the first treatment period and received one matching placebo capsule BID during the second treatment period. The 2 treatment periods were separated by a 3-week washout period.
Drug: Preladenant
capsules
Other Names:
  • SCH 420814
  • MK-3814
Placebo Comparator: Placebo BID→Preladenant 25 mg BID
Participants received one matching placebo capsule BID for 14 days during the first treatment period and received one preladenant 25 mg capsule during the second treatment period. The 2 treatment periods were separated by a 3-week washout period.
Drug: Placebo
capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lowest Extrapyramidal Symptom Rating Score (ESRS) Total Score Within the 6-hour Evaluation on Day 14 of Each Treatment Period
Time Frame: Up to 6 hours post-dose on Day 14
The ESRS total score consists of 4 subscales: 1) a questionnaire of extrapyramidal symptoms (EPS) and drug-induced movement disorders (DIMD) over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). The ESRS total score could range from 0 to 225, with a lower score reflecting a better outcome. The lowest ESRS total score for each participant within the 6-hour range on Day 14 was analyzed.
Up to 6 hours post-dose on Day 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean ESRS Total Scores Within the 6-hour Evaluation on Day 14 of Each Treatment Period
Time Frame: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
The ESRS total score consists of 4 subscales: 1) a questionnaire of EPS and DIMD over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). The ESRS total score could range from 0 to 225, with a lower score reflecting a better outcome. The mean ESRS total scores at Hours 1, 2, 3, 4, 5, and 6 on Day 14 were analyzed.
1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
Lowest ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period
Time Frame: Up to 6 hours post-dose on Day 14
The ESRS consists of 4 subscales: 1) a questionnaire of EPS and DIMD over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). A lower subscale score reflects a better outcome. The lowest subscale score on Day 14 was analyzed.
Up to 6 hours post-dose on Day 14
Mean ESRS Part I Subscore: EPS and DIMD Within the 6-hour Evaluation on Day 14 of Each Treatment Period
Time Frame: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
The ESRS consists of 4 subscales: 1) a questionnaire of EPS and DIMD over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). A lower subscale score reflects a better outcome. The mean subscores at Hours 1, 2, 3, 4, 5 and 6 on Day 14 were analyzed.
1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
Lowest ESRS Part II Subscore: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
Time Frame: Up to 6 hours post-dose on Day 14
The ESRS consists of 4 subscales: 1) a questionnaire of EPS and DIMD over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). A lower subscale score reflects a better outcome. The lowest subscale score on Day 14 was analyzed.
Up to 6 hours post-dose on Day 14
Mean ESRS Part II Subscores: Parkinsonism and Akathisia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
Time Frame: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
The ESRS consists of 4 subscales: 1) a questionnaire of EPS and DIMD over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). A lower subscale score reflects a better outcome. The mean subscores at Hours 1, 2, 3, 4, 5 and 6 on Day 14 were analyzed.
1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
Lowest ESRS Part III Subscore: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
Time Frame: Up to 6 hours post-dose on Day 14
The ESRS consists of 4 subscales: 1) a questionnaire of EPS and DIMD over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). A lower subscale score reflects a better outcome. The lowest subscale score on Day 14 was analyzed.
Up to 6 hours post-dose on Day 14
Mean ESRS Part III Subscores: Dystonia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
Time Frame: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
The ESRS consists of 4 subscales: 1) a questionnaire of EPS and DIMD over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). A lower subscale score reflects a better outcome. The mean subscores at Hours 1, 2, 3, 4, 5 and 6 on Day 14 were analyzed.
1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
Lowest ESRS Part IV Subscore: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
Time Frame: Up to 6 hours post-dose on Day 14
The ESRS consists of 4 subscales: 1) a questionnaire of EPS and DIMD over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). A lower subscale score reflects a better outcome. The lowest subscale score on Day 14 was analyzed.
Up to 6 hours post-dose on Day 14
Mean ESRS Part IV Subscores: Dyskinesia Within the 6-hour Evaluation on Day 14 of Each Treatment Period
Time Frame: 1, 2, 3, 4, 5, and 6 hours post-dose on Day 14
The ESRS consists of 4 subscales: 1) a questionnaire of EPS and DIMD over the previous 7 days (7 items scored as 0=Absent to 3=Severe; score range: 0-21), 2) an examination of Parkinsonism and akathisia (17 items scored as 0=None to 6=Severe; score range: 0-102), 3) an examination of dystonia (10 items scored as 0=Absent to 6=Most Severe; score range 0-60) and 4) an examination of dyskinesia (7 items scored as 0=None to 6=Severe; score range: 0-42). A lower subscale score reflects a better outcome. The mean subscores at Hours 1, 2, 3, 4, 5 and 6 on Day 14 were analyzed.
1, 2, 3, 4, 5, and 6 hours post-dose on Day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2006

Primary Completion (Actual)

March 6, 2008

Study Completion (Actual)

March 6, 2008

Study Registration Dates

First Submitted

May 27, 2008

First Submitted That Met QC Criteria

May 29, 2008

First Posted (Estimate)

May 30, 2008

Study Record Updates

Last Update Posted (Actual)

November 9, 2018

Last Update Submitted That Met QC Criteria

October 10, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P04628
  • 2005-006048-42 (EudraCT Number)
  • MK-3814-014 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

  1. CSR Synopsis

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe