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

NCT00693472 | Terminated Phase 2 Results

• 2 other identifiers: P05145MK-3814-019
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Akathisia, Drug-Induced; Antipsychotic Agents; Movement Disorders

Keywords

Antipsychotic Agents

Outcome Measures

Primary Outcomes (2)

• Part 1: Number of Participants With Akathisia

  Incidence of akathisia is reported as the number of participants who experienced akathisia. Akathisia is defined as a score of 3 on the Barnes akathisia scale (BAS) for 3 consecutive intervals or an akathisia score (BAS) of ≥4 for any single day, or the use of a rescue medication within 13 days of initiating treatment with haloperidol and preladenant. The BAS is scored as follows: objective akathisia, subjective awareness of restlessness and subjective distress related to restlessness are rated on a 4-point scale from 0 - 3 and are summed yielding a total score ranging from 0 (no akathisia) to 9 (severe akathisia).

  Up to 13 days

• Part 2: Number of Participants Who Were Treatment Failures

  Incidence of treatment failure is reported as the number of participants who were treatment failures. A treatment failure is defined as the failure to achieve at least a 1 point reduction from baseline in BAS score at 24 to 26 hours following study treatment. The BAS is scored as follows: objective akathisia, subjective awareness of restlessness and subjective distress related to restlessness are rated on a 4-point scale from 0 - 3 and are summed yielding a total score ranging from 0 (no akathisia) to 9 (severe akathisia).

  Up to 14 days

Secondary Outcomes (4)

• Part 1: Mean Global Clinical Impression at Day 14

  Day 14 of Part 1

• Part 1: Mean Positive and Negative Symptom Scale for Schizophrenia (PANSS) Total Score at Day 14

  Day 14 of Part 1

• Part 2: Mean GCI at Day 14

  Day 14 of Part 2

• Part 2: PANSS Total Score at Day 14

  Day 14 of Part 2

Study Arms (4)

Part 1: Preladenant

EXPERIMENTAL

Preladenant 25 mg every 12 hours for 13 days

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

Part 1: Placebo

PLACEBO COMPARATOR

Placebo every 12 hours for 13 days

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

Part 2: Preladenant

EXPERIMENTAL

Preladenant 25 mg every 12 hours for 13 days

Drug: Preladenant; Drug: Haloperidol

Part 2: Standard of Care

ACTIVE COMPARATOR

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

Drug: Anticholinergic agents or propanolol; Drug: Haloperidol

Interventions

Preladenant DRUG

Preladenant, one 25 mg capsule, administered orally every 12 hours

Also known as: SCH 420814

Part 1: Preladenant; Part 2: Preladenant

Placebo DRUG

Matching placebo capsule administered orally every 12 hours

Part 1: Placebo

Anticholinergic agents or propanolol DRUG

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.

Part 1: Placebo; Part 1: Preladenant; Part 2: Standard of Care

Haloperidol DRUG

Participants continued pre-study haloperidol, admistered orally, at a dose of at least 7.5 mg/day

Part 1: Placebo; Part 1: Preladenant; Part 2: Preladenant; Part 2: Standard of Care

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Akathisia, Drug-Induced; Movement Disorders

Interventions

2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine; Cholinergic Antagonists; Propranolol; Haloperidol

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Neurotoxicity Syndromes; Psychomotor Agitation; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Poisoning

Intervention Hierarchy (Ancestors)

Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Butyrophenones; Ketones

Limitations and Caveats

The study was terminated early by the sponsor due to lack of enrollment.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2008
• First Posted: June 9, 2008
• Study Start: August 15, 2007
• Primary Completion: December 12, 2008
• Study Completion: January 9, 2009
• Last Updated: November 7, 2018
• Results First Posted: May 24, 2017

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share