Study of Preladenant for the Treatment of Neuroleptic Induced Akathisia (Study P05145)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 2

Conditions: Antipsychotic Agents; Movement Disorders; Akathisia, Drug-Induced

Treatments: Drug: Placebo; Drug: Haloperidol; Drug: Anticholinergic agents or propanolol; Drug: Preladenant

Study type: Interventional

Funder types: Industry

Identifiers

NCT00693472

MK-3814-019 (Other Identifier)

P05145

Details and patient eligibility

About

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.

Enrollment: 46 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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46 participants in 4 patient groups, including a placebo group

Part 1: Preladenant

Experimental group

Description:

Preladenant 25 mg every 12 hours for 13 days

Treatment:

Drug: Preladenant

Drug: Anticholinergic agents or propanolol

Drug: Haloperidol

Part 1: Placebo

Placebo Comparator group

Description:

Placebo every 12 hours for 13 days

Treatment:

Drug: Placebo

Drug: Anticholinergic agents or propanolol

Drug: Haloperidol

Part 2: Preladenant

Experimental group

Description:

Preladenant 25 mg every 12 hours for 13 days

Treatment:

Drug: Preladenant

Drug: Haloperidol

Part 2: Standard of Care

Active Comparator group

Description:

Anticholinergic agents or Propranolol as standard-of-care dosing regimen (supplied by the study site)

Treatment:

Drug: Anticholinergic agents or propanolol

Drug: Haloperidol