Akathisia, Drug-InducedPhase 2NCT00693472
Study of Preladenant for the Treatment of Neuroleptic Induced Akathisia (Study P05145)
A Phase 2 study testing Preladenant, Anticholinergic agents or propanolol and Haloperidol in people with Akathisia, Drug-Induced and Antipsychotic Agents, run by Merck Sharp & Dohme LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Akathisia, Drug-Induced, Antipsychotic Agents, Movement Disorders
- What is being tested?
- Preladenant, Anticholinergic agents or propanolol and Haloperidol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- No sites listed yet
- Study dates
- 15 Aug 2007to 9 Jan 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
About this study
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 participants with acute psychosis using the Barnes Akathisia Scale.
- Being tested
- Preladenant, Placebo, Anticholinergic agents or propanolol, Haloperidol
- Keywords
- Antipsychotic Agents
- Medical subject headings
- Akathisia, Drug-Induced, Movement Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PreladenantDrug
Also called SCH 420814
Preladenant, one 25 mg capsule, administered orally every 12 hours
PlaceboDrug
Matching placebo capsule administered orally every 12 hours
Anticholinergic agents or propanololDrug
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.
HaloperidolDrug
Participants continued pre-study haloperidol, admistered orally, at a dose of at least 7.5 mg/day
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Preladenant | Experimental | Preladenant 25 mg every 12 hours for 13 days Receives: Drug: Preladenant; Drug: Anticholinergic agents or propanolol; Drug: Haloperidol |
| Part 1: Placebo | Placebo comparator | Placebo every 12 hours for 13 days Receives: Drug: Placebo; Drug: Anticholinergic agents or propanolol; Drug: Haloperidol |
| Part 2: Preladenant | Experimental | Preladenant 25 mg every 12 hours for 13 days Receives: 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) Receives: Drug: Anticholinergic agents or propanolol; Drug: Haloperidol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: Up to 14 days
Secondary outcomes (4)
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).
Measured: Day 14 of Part 1
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).
Measured: Day 14 of Part 1
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).
Measured: Day 14 of Part 2
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).
Measured: Day 14 of Part 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2008 (estimated)
- Study start15 Aug 2007
- Primary completion12 Dec 2008
- Study completion9 Jan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Akathisia, Drug-InducedStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00693472
- Sponsor's protocol ID
- P05145
- Other IDs
- MK-3814-019
- Status last verified
- Oct 2018
- First submitted
- 27 May 2008
- Last updated
- 7 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of SCH 420814 to Reduce the Frequency or Severity of Neuroleptic Induced Akathisia
- ClinicalTrials.gov ID
- NCT00693472
- Acronym / sponsor ID
- P05145
- Keywords
- Antipsychotic Agents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 15 Aug 2007 (actual)
- Primary completion
- 12 Dec 2008 (actual)
- Study completion
- 9 Jan 2009 (actual)
- First posted
- 9 Jun 2008 (estimated)
- Results
- Posted 24 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1: Preladenant | Experimental | Drug: Preladenant, Drug: Anticholinergic agents or propanolol, Drug: HaloperidolPreladenant 25 mg every 12 hours for 13 days |
| Part 1: Placebo | Placebo comparator | Drug: Placebo, Drug: Anticholinergic agents or propanolol, Drug: HaloperidolPlacebo every 12 hours for 13 days |
| Part 2: Preladenant | Experimental | Drug: Preladenant, Drug: HaloperidolPreladenant 25 mg every 12 hours for 13 days |
| Part 2: Standard of Care | Active comparator | Drug: Anticholinergic agents or propanolol, Drug: HaloperidolAnticholinergic agents or Propranolol as standard-of-care dosing regimen (supplied by the study site) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PreladenantAlso: SCH 420814Preladenant, one 25 mg capsule, administered orally every 12 hours | Drug | Part 1: Preladenant, Part 2: Preladenant |
| PlaceboMatching placebo capsule administered orally every 12 hours | Drug | Part 1: Placebo |
| Anticholinergic agents or propanololPart 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. | Drug | Part 1: Placebo, Part 1: Preladenant, Part 2: Standard of Care |
| HaloperidolParticipants continued pre-study haloperidol, admistered orally, at a dose of at least 7.5 mg/day | Drug | Part 1: Placebo, Part 1: Preladenant, Part 2: Preladenant, Part 2: Standard of Care |
Primary outcome
Part 1: Number of Participants With Akathisia
Time frame: Up to 13 days
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
Time frame: Up to 14 days
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).
4 secondary outcomes
Part 1: Mean Global Clinical Impression at Day 14
Time frame: Day 14 of Part 1
Part 1: Mean Positive and Negative Symptom Scale for Schizophrenia (PANSS) Total Score at Day 14
Time frame: Day 14 of Part 1
Part 2: Mean GCI at Day 14
Time frame: Day 14 of Part 2
Part 2: PANSS Total Score at Day 14
Time frame: Day 14 of Part 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Preladenant, Anticholinergic agents or propanolol and Haloperidol in people with Akathisia, Drug-Induced and Antipsychotic Agents, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Number of Participants With Akathisia (time frame: Up to 13 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2018.