Official Title: “Efficacy of SCH 420814 to Reduce the Frequency or Severity of Neuroleptic Induced Akathisia”

This study is designed to evaluate the effectiveness of preladenant in the prevention (Part 1) or treatment (Part 2) of antipsychotic induced akathisia in subjects with acute psychosis using the Barnes Akathisia Scale.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Outcomes Assessor), Placebo Control, Parallel Assignment, Pharmacodynamics Study

Study Primary Completion Date: December 2008

Intervention(s) in this Clinical Trial

• Drug: Preladenant
  • one 25 mg capsule twice daily for 13 days
• Drug: Placebo
  • Matching placebo capsule twice daily for 13 days
• Drug: Preladenant
  • one 25 mg capsule twice daily for 13 days
• Drug: Anticholinergic agents or propanolol
  • Standard of care; Anticholinergic agents or propanolol as determined by the investigator according to the local standard of care

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Part 1: Treatment A Preladenant
• Placebo Comparator: Part 1: Treatment B Placebo
• Experimental: Part 2: Treatment C Preladenant
• Active Comparator: Part 2: Treatment D Standard of Care

Primary Measures

• Part 1: Incidence of akathisia; Part 2: Incidence of treatment failure
  • Time Frame: Day 13
    Safety Issue?: No

Secondary Measures

• Part 1 only: number of subjects that have a prevention failure (defined as the onset of akathisia)
  • Time Frame: Day 13
    Safety Issue?: No
• Part 1: Global Clinical Impression, positive and negative symptom scale for schizophrenia (PANSS) Part 2: Global Clinical Impression, positive and negative symptom scale for schizophrenia (PANSS)
  • Time Frame: Daily
    Safety Issue?: No

Inclusion Criteria:

• Subjects or guardian must be willing to give written informed consent.
• Part 1 Only: Subjects with acute (not drug related) psychoses with a PANSS score of at least 60: schizophrenia, schizo-affective, schizo-manic, and acute mania with a history of previous treatment with neuroleptics.
• Part 1 Only: Subjects initiating haloperidol for the treatment of an acute psychotic episode at a dose of at least 7.5 mg per day.
• Part 2 Only: Inpatient subjects who have developed akathisia as a result of haloperidol at >=5 mg per day for the treatment of acute psychosis. The enrollment of subjects receiving other neuroleptics is allowed only after consultation and agreement by the sponsor.
• Subjects of either sex and of any race between the ages of 18 and 65 years, inclusive.
• Subjects' clinical laboratory tests (CBC, blood chemistry, and urinalysis) must be within normal limits or clinically acceptable to the investigator/sponsor. Subject's liver function test results (ie, AST, ALT) must not be elevated above the normal limits at Screening and on Day -1/1.
• Subjects must be free of any clinically significant disease other than psychosis that would interfere with the study evaluations.
• Screening ECG must be clinically acceptable to the investigator.
• Female of childbearing potential must:
• Have used a medically accepted method of contraception for 1 month (or abstained from sexual intercourse) prior to the screening period. An acceptable method of contraception includes one of the following:
• condom (male or female) ~ spermicide,
• diaphragm or cervical cap ~ spermicide and condom,
• stable oral/transdermal/injectable hormonal contraceptive regimen without breakthrough uterine bleeding for 2 months prior to Screening visit and a condom ~ spermicide,
• intrauterine device (inserted at least 2 months prior to Screening visit) used spermicide.
• Note: Vasectomy of the partner is not considered sufficient contraception and one of the 4 bulleted methods listed above must be used.
• Agree to use one of the accepted methods of contraception (listed above) during the trial (including the screening period prior to receiving trial medication), and for 1 month after stopping the trial medication.
• Subjects enrolled in the placebo arm of Part 1 and who developed akathisia may be eligible for Part 2 in the standard of care arm.

Exclusion Criteria:

• Subjects who have a positive screen for drugs with a high potential for abuse.
• Subjects that screen positive for cannabis are permitted.
• Subjects who have previously received this compound.
• Subjects who are currently participating in another clinical study or have participated in a clinical study within 30 days (excepted subjects enrolled in the Part 1 of the P05145 study).
• Subjects who are part of the study staff personnel or family members of the study staff personnel.
• Subjects with severe/uncontrolled hypertension will be excluded. Subjects with hypertension well controlled on a stable dose of standard antihypertensive medication (excluding beta-blockers) will be eligible.
• Subjects with history of coronary artery disease including MI, or cerebrovascular disease (stroke, TIA), or peripheral arterial disease.
• Subjects with congestive heart failure or subjects with ECGs consistent with ischemic heart disease, sick sinus syndrome or significant Q waves.
• Subjects who are found to be at immediate risk of suicide.
• Female subjects pregnant or nursing.
• Subjects treated by Clozapine will be excluded. A washout period of 6 months prior to dosing will be acceptable for study entry.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Schering-Plough

Overall Clinical Trial Officials and Contacts

Overall Contact: SP Clinical Trial Registry Call Center 1-888-772-8734 

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00693472

Study ID Number: P05145

ClinicalTrials.gov Identifier: NCT00693472

Health Authority: South Africa: Medicines Control Council