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| ID | Type | Description | Link |
|---|---|---|---|
| MK-3814-019 | Other Identifier | Merck protocol number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Preladenant | Experimental | Preladenant 25 mg every 12 hours for 13 days |
|
| Part 1: Placebo | Placebo Comparator | Placebo every 12 hours for 13 days |
|
| Part 2: Preladenant | Experimental | Preladenant 25 mg every 12 hours for 13 days |
|
| Part 2: Standard of Care | Active Comparator | Anticholinergic agents or Propranolol as standard-of-care dosing regimen (supplied by the study site) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Preladenant | Drug | Preladenant, one 25 mg capsule, administered orally every 12 hours |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Day 14 of Part 1 |
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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:
Note: Vasectomy of the partner is not considered sufficient contraception and one of the 4 bulleted methods listed above must be used.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: Preladenant | Preladenant 25 mg every 12 hours for 13 days |
| FG001 | Part 1: Placebo | Placebo every 12 hours for 13 days |
| FG002 | Part 2: Preladenant | Preladenant 25 mg every 12 hours for 13 days |
| FG003 | Part 2: Standard of Care | Anticholinergic agents or Propranolol as standard-of-care dosing regimen (supplied by the study site) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 |
|
| ||||||||||||||||||
| Part 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: Preladenant | Preladenant 25 mg every 12 hours for 13 days |
| BG001 | Part 1: Placebo | Placebo every 12 hours for 13 days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Efficacy analysis population was defined as participants who received at least one dose of study drug. | Posted | Number | Participants | Up to 13 days |
|
Up to 22 days (including follow-up)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1: Placebo | Placebo every 12 hours for 13 days |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| NEUTROPENIA | Blood and lymphatic system disorders | MedDRA 11.1 | Systematic Assessment |
The study was terminated early by the sponsor due to lack of enrollment.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D017109 | Akathisia, Drug-Induced |
| D009069 | Movement Disorders |
| ID | Term |
|---|---|
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020258 | Neurotoxicity Syndromes |
| D011595 | Psychomotor Agitation |
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| ID | Term |
|---|---|
| C539997 | 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 |
| D018680 | Cholinergic Antagonists |
| D011433 | Propranolol |
| D006220 | Haloperidol |
| ID | Term |
|---|---|
| D018678 | Cholinergic Agents |
| D018377 | Neurotransmitter Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
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| Placebo | Drug | Matching placebo capsule administered orally every 12 hours |
|
| 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. |
|
| Haloperidol | Drug | Participants continued pre-study haloperidol, admistered orally, at a dose of at least 7.5 mg/day |
|
| 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). |
| 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). | 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). | Day 14 of Part 2 |
| Lost to Follow-up |
|
| Withdrew - reason unrelated to treatment |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| BG002 | Part 2: Preladenant | Preladenant 25 mg every 12 hours for 13 days |
| BG003 | Part 2: Standard of Care | Anticholinergic agents or Propranolol as standard-of-care dosing regimen (supplied by the study site) |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Part 1: Placebo | Placebo every 12 hours for 13 days |
|
|
| Primary | 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). | Efficacy analysis population was defined as participants who received at least one dose of study drug. | Posted | Number | Participants | Up to 14 days |
|
|
|
| Secondary | 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). | Efficacy analysis population was defined as participants who received at least one dose of study drug. The study was terminated early by the sponsor due to lack of enrollment. No formal statistical analysis was done due to the very small sample size in this study. | Posted | Mean | Standard Deviation | Score on a scale | Day 14 of Part 1 |
|
|
|
| Secondary | 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). | Efficacy analysis population was defined as participants who received at least one dose of study drug. The study was terminated early by the sponsor due to lack of enrollment. No formal statistical analysis was done due to the very small sample size in this study. | Posted | Mean | Standard Deviation | Score on a scale | Day 14 of Part 1 |
|
|
|
| Secondary | 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). | Efficacy analysis population was defined as participants who received at least one dose of study drug. The study was terminated early by the sponsor due to lack of enrollment. No formal statistical analysis was done due to the very small sample size in this study. | Posted | Mean | Standard Deviation | Score on a scale | Day 14 of Part 2 |
|
|
|
| Secondary | 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). | Efficacy analysis population was defined as participants who received at least one dose of study drug. The study was terminated early by the sponsor due to lack of enrollment. No formal statistical analysis was done due to the very small sample size in this study. | Posted | Mean | Standard Deviation | Score on a scale | Day 14 of Part 2 |
|
|
|
| 0 |
| 13 |
| 12 |
| 13 |
| EG001 | Part 1: Preladenant | Preladenant 25 mg every 12 hours for 13 days | 0 | 19 | 16 | 19 |
| EG002 | Part 2: Standard of Care | Anticholinergic agents or Propranolol as standard-of-care dosing regimen (supplied by the study site) | 0 | 6 | 6 | 6 |
| EG003 | Part 2: Preladenant | Preladenant 25 mg every 12 hours for 13 days | 0 | 8 | 7 | 8 |
| TACHYCARDIA | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
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| CONJUNCTIVAL HYPERAEMIA | Eye disorders | MedDRA 11.1 | Systematic Assessment |
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| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| CONSTIPATION | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| SALIVARY HYPERSECRETION | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| VOMITING | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| FATIGUE | General disorders | MedDRA 11.1 | Systematic Assessment |
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| MALAISE | General disorders | MedDRA 11.1 | Systematic Assessment |
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| ABSCESS ORAL | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| RHINITIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| TINEA PEDIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| TONSILLITIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| SKIN LACERATION | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
|
| SOFT TISSUE INJURY | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
|
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| LIVER FUNCTION TEST ABNORMAL | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| NEUTROPHIL COUNT DECREASED | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| WEIGHT INCREASED | Investigations | MedDRA 11.1 | Systematic Assessment |
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| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| JOINT STIFFNESS | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| MUSCLE SPASMS | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| MUSCULOSKELETAL STIFFNESS | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| NECK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| PAIN IN JAW | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| AKATHISIA | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| COGWHEEL RIGIDITY | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| DISTURBANCE IN ATTENTION | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| DYSKINESIA | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| DYSTONIA | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| EXTRAPYRAMIDAL DISORDER | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| HEAD TITUBATION | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| HYPERTONIA | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| OROMANDIBULAR DYSTONIA | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| SOMNOLENCE | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| TENSION HEADACHE | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| TREMOR | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| AFFECTIVE DISORDER | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
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| AGITATION | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
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| ANXIETY | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
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| INSOMNIA | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
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| PARANOIA | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
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| SCHIZOPHRENIA | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
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| HYPERTENSION | Vascular disorders | MedDRA 11.1 | Systematic Assessment |
|
The investigator agrees not to publish or publicly present any interim results of the study without the prior written consent of the Sponsor. The investigator further agrees to provide to the Sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study.
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011041 | Poisoning |
| D020164 | Chemical Actions and Uses |
| D045505 | Physiological Effects of Drugs |
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D002090 | Butyrophenones |
| D007659 | Ketones |