Study of Preladenant for the Treatment of Neuroleptic Induced Akathisia (Study P05145)
Condition: Akathisia, Drug-Induced; Antipsychotic Agents; Movement Disorders
MeSH terms: Movement Disorders; Psychomotor Agitation; Akathisia, Drug-Induced
Intervention: Preladenant; Placebo; Anticholinergic agents or propanolol; Haloperidol
Intervention description: Preladenant, one 25 mg capsule, administered orally every 12 hours; Matching placebo capsule administered orally every 12 hours; Part 1 (as rescue therapy only): participants who develop akathisias may be treated with either anticholinergic agents or propranolol as a rescue medication at the discretion of the treating physician. Individual anticholinergic agents were not pre-specified per protocol.
Part 2 (standard of care): anticholinergic agents or propanolol at a dose determined by the investigator according to the local standard of care. Individual anticholinergic agents were not pre-specified per protocol.; Participants continued pre-study haloperidol, admistered orally, at a dose of at least 7.5 mg/day
Intervention MeSH terms: Propranolol; Haloperidol; Haloperidol decanoate; Cholinergic Antagonists
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Antipsychotic Agents

Summary:

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

Eligibility criteria:

        Inclusion Criteria:

          -  Participants or guardian must be willing to give written informed consent.

          -  Part 1 Only: Participants with acute (not drug related) psychoses with a Positive and
             Negative Symptom Scale for Schizophrenia (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: Participants 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 participants who have developed akathisia as a result of
             haloperidol at >=5 mg per day for the treatment of acute psychosis. The enrollment of
             participants receiving other neuroleptics is allowed only after consultation and
             agreement by the sponsor.

          -  Participants of either sex and of any race between the ages of 18 and 65 years,
             inclusive.

          -  Participant's clinical laboratory tests (complete blood count [CBC], blood chemistry,
             and urinalysis) must be within normal limits or clinically acceptable to the
             investigator/sponsor. Participant's liver function test results (ie, aspartate
             aminotransferase [AST], alanine aminotransferase [ALT]) must not be elevated above the
             normal limits at Screening and on Day -1/1.

          -  Participants must be free of any clinically significant disease other than psychosis
             that would interfere with the study evaluations.

          -  Screening electrocardiogram (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) used with spermicide,

                    -  diaphragm or cervical cap used with spermicide and condom,

                    -  stable oral/transdermal/injectable hormonal contraceptive regimen without
                       breakthrough uterine bleeding for 2 months prior to Screening visit and a
                       condom used with spermicide,

                    -  intrauterine device (inserted at least 2 months prior to Screening visit)
                       used with 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.

          -  Participants 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:

          -  Participants who have a positive screen for drugs with a high potential for abuse.
             Participants that screen positive for cannabis are permitted.

          -  Participants who have previously received this compound.

          -  Participants who are currently participating in another clinical study or have
             participated in a clinical study within 30 days (except participants enrolled in the
             Part 1 of the P05145 study).

          -  Participants who are part of the study staff personnel or family members of the study
             staff personnel.

          -  Participants with severe/uncontrolled hypertension will be excluded. Participants with
             hypertension well controlled on a stable dose of standard antihypertensive medication
             (excluding beta-blockers) will be eligible.

          -  Participants with history of coronary artery disease including myocardial infarction
             (MI), or cerebrovascular disease (stroke, transient ischemic attack [TIA]), or
             peripheral arterial disease.

          -  Participants with congestive heart failure or participants with ECGs consistent with
             ischemic heart disease, sick sinus syndrome or significant Q waves.

          -  Participants who are found to be at immediate risk of suicide.

          -  Female participants pregnant or nursing.

          -  Participants treated by Clozapine will be excluded. A washout period of 6 months prior
             to dosing will be acceptable for study entry.