Back to resultsStudy of Preladenant for the Treatment of Neuroleptic Induced Akathisia (Study P05145)
Primary Purpose
Akathisia, Drug-Induced, Antipsychotic Agents, Movement Disorders
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Preladenant
Placebo
Anticholinergic agents or propanolol
Haloperidol
Sponsored by
About this trial
This is an interventional treatment trial for Akathisia, Drug-Induced focused on measuring Antipsychotic Agents
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Active Comparator
Arm Label
Part 1: Preladenant
Part 1: Placebo
Part 2: Preladenant
Part 2: Standard of Care
Arm Description
Preladenant 25 mg every 12 hours for 13 days
Placebo every 12 hours for 13 days
Preladenant 25 mg every 12 hours for 13 days
Anticholinergic agents or Propranolol as standard-of-care dosing regimen (supplied by the study site)
Outcomes
Primary Outcome Measures
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).
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).
Secondary Outcome Measures
Part 1: Mean Global Clinical Impression at Day 14
Global clinical impression (GCI) was administered to assess whether any deterioration is due to akathisia or uncontrolled psychoses. Score on a scale +2 to -2 (+2 represents much improvement, +1 some improvement, 0 no change, -1 some worsening, and -2 much worsening).
Part 1: Mean Positive and Negative Symptom Scale for Schizophrenia (PANSS) Total Score at Day 14
The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal).
For each item, symptom severity was rated on a 7-point scale, from 0=absent to 6=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 0 to 180 with a higher score indicating greater severity of symptoms. Although the PANSS is traditionally scored with a range of 30-210, with a score of absent = 1 (for each item), for this analysis the range was set from 0-180, with a score of absent = 0 (for each item).
Part 2: Mean GCI at Day 14
The GCI was administered to assess whether any deterioration is due to akathisia or uncontrolled psychoses. Score on a scale +2 to -2 (+2 represents much improvement, +1 some improvement, 0 no change, -1 some worsening, and -2 much worsening).
Part 2: PANSS Total Score at Day 14
The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 0=absent to 6=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 0 to 180 with a higher score indicating greater severity of symptoms. Although the PANSS is traditionally scored with a range of 30-210, with a score of absent = 1 (for each item), for this analysis the range was set from 0-180, with a score of absent = 0 (for each item).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00693472
Brief Title
Study of Preladenant for the Treatment of Neuroleptic Induced Akathisia (Study P05145)
Official Title
Efficacy of SCH 420814 to Reduce the Frequency or Severity of Neuroleptic Induced Akathisia
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Terminated
Study Start Date
August 15, 2007 (Actual)
Primary Completion Date
December 12, 2008 (Actual)
Study Completion Date
January 9, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Akathisia, Drug-Induced, Antipsychotic Agents, Movement Disorders
Keywords
Antipsychotic Agents
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1: Preladenant
Arm Type
Experimental
Arm Description
Preladenant 25 mg every 12 hours for 13 days
Arm Title
Part 1: Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo every 12 hours for 13 days
Arm Title
Part 2: Preladenant
Arm Type
Experimental
Arm Description
Preladenant 25 mg every 12 hours for 13 days
Arm Title
Part 2: Standard of Care
Arm Type
Active Comparator
Arm Description
Anticholinergic agents or Propranolol as standard-of-care dosing regimen (supplied by the study site)
Intervention Type
Drug
Intervention Name(s)
Preladenant
Other Intervention Name(s)
SCH 420814
Intervention Description
Preladenant, one 25 mg capsule, administered orally every 12 hours
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo capsule administered orally every 12 hours
Intervention Type
Drug
Intervention Name(s)
Anticholinergic agents or propanolol
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Haloperidol
Intervention Description
Participants continued pre-study haloperidol, admistered orally, at a dose of at least 7.5 mg/day
Primary Outcome Measure Information:
Title
Part 1: Number of Participants With Akathisia
Description
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).
Time Frame
Up to 13 days
Title
Part 2: Number of Participants Who Were Treatment Failures
Description
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).
Time Frame
Up to 14 days
Secondary Outcome Measure Information:
Title
Part 1: Mean Global Clinical Impression at Day 14
Description
Global clinical impression (GCI) was administered to assess whether any deterioration is due to akathisia or uncontrolled psychoses. Score on a scale +2 to -2 (+2 represents much improvement, +1 some improvement, 0 no change, -1 some worsening, and -2 much worsening).
Time Frame
Day 14 of Part 1
Title
Part 1: Mean Positive and Negative Symptom Scale for Schizophrenia (PANSS) Total Score at Day 14
Description
The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal).
For each item, symptom severity was rated on a 7-point scale, from 0=absent to 6=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 0 to 180 with a higher score indicating greater severity of symptoms. Although the PANSS is traditionally scored with a range of 30-210, with a score of absent = 1 (for each item), for this analysis the range was set from 0-180, with a score of absent = 0 (for each item).
Time Frame
Day 14 of Part 1
Title
Part 2: Mean GCI at Day 14
Description
The GCI was administered to assess whether any deterioration is due to akathisia or uncontrolled psychoses. Score on a scale +2 to -2 (+2 represents much improvement, +1 some improvement, 0 no change, -1 some worsening, and -2 much worsening).
Time Frame
Day 14 of Part 2
Title
Part 2: PANSS Total Score at Day 14
Description
The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 0=absent to 6=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 0 to 180 with a higher score indicating greater severity of symptoms. Although the PANSS is traditionally scored with a range of 30-210, with a score of absent = 1 (for each item), for this analysis the range was set from 0-180, with a score of absent = 0 (for each item).
Time Frame
Day 14 of Part 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Learn more about this trial
Study of Preladenant for the Treatment of Neuroleptic Induced Akathisia (Study P05145)
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