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| ID | Type | Description | Link |
|---|---|---|---|
| 2009_519 |
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A study to evaluate the safety and efficacy of treatment with MK-8998 as compared to placebo and olanzapine for acutely psychotic patients with schizophrenia. The primary hypothesis is that in participants undergoing an acute psychotic episode of schizophrenia, MK-8998 6 to 8 mg twice daily is superior to placebo in the treatment of symptoms of schizophrenia as measured by the mean change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Week 4.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MK-8998 | Experimental | MK-8998, 6 mg twice a day (BID) for Days 1 to 7, and 8 mg BID thereafter for a 4-week total treatment period |
|
| Olanzapine | Active Comparator | Olanzapine, 5 mg BID for Day 1 to 7, and 15 mg (5 mg in the morning and 10 mg in the evening) thereafter for a 4-week total treatment period |
|
| Placebo | Placebo Comparator | Placebo Comparator to MK-8998 or olanzapine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-8998 | Drug | MK-8998 6 mg capsules twice daily with food on Days 1 through 7. On Day 8, dosage will be increased to 8 mg capsules twice daily. Treatment period is 4 weeks. There will be a period of time when all participants will receive placebo. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) at Week 4 | PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. PANSS measure is composed of 3 scales: Positive scale, Negative scale, and General Psychopathology scale. Positive scale assesses hallucinations, delusions and related symptoms; Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms; and General Psychopathology scale addresses other symptoms such as anxiety, somatic concern and disorientation. The PANSS has 30 items in its 3 scales and an anchored Likert scale from 1 to 7 is used to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. The Positive scale has 7 items with a score from 7 to 49, the Negative scale has 7 items with a score from 7 to 49, and the General Psychopathology scale has 16 items with a score from 16 to 112. A total score is the sum of the 3 scores for the 3 scales. | Baseline and Week 4 |
| Number of Participants Who Experienced at Least One Adverse Event | An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug. | Up to 6 Weeks |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug. | Up to 4 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Response at Week 4 | Responders were defined as participants who demonstrated ≥ 20% improvement from baseline on the PANSS total score. PANSS measure is composed of 3 scales: Positive scale, Negative scale, and General Psychopathology scale. Positive scale assesses hallucinations, delusions and related symptoms; Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms; and General Psychopathology scale addresses other symptoms such as anxiety, somatic concern and disorientation. The PANSS has 30 items in its 3 scales and an anchored Likert scale from 1 to 7 is used to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. The Positive scale has 7 items with a score from 7 to 49, the Negative scale has 7 items with a score from 7 to 49, and the General Psychopathology scale has 16 items with a score from 16 to 112. A total score is the sum of the 3 scores for the 3 scales. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23532746 | Derived | Egan MF, Zhao X, Smith A, Troyer MD, Uebele VN, Pidkorytov V, Cox K, Murphy M, Snavely D, Lines C, Michelson D. Randomized controlled study of the T-type calcium channel antagonist MK-8998 for the treatment of acute psychosis in patients with schizophrenia. Hum Psychopharmacol. 2013 Mar;28(2):124-33. doi: 10.1002/hup.2289. |
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Participants who met entry criteria were washed out of psychotropic medication and then entered a single-blind, in-patient, 3-day to 7-day, placebo lead-in period.
Male and female inpatients who were experiencing an acute exacerbation of schizophrenia were randomized at 21 sites worldwide.
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| ID | Title | Description |
|---|---|---|
| FG000 | MK-8998 | MK-8998, 6 mg twice a day (BID) on Days 1 to 7, and 8 mg BID thereafter for a 4-week total treatment period |
| FG001 | Olanzapine | Olanzapine, 5 mg BID on Day 1 to 7, and 15 mg (5 mg in the morning and 10 mg in the evening) thereafter for a 4-week total treatment period |
| FG002 | Placebo Comparator | Placebo Comparator to MK-8998 or olanzapine |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | MK-8998 | MK-8998, 6 mg twice a day (BID) on Days 1 to 7, and 8 mg BID thereafter for a 4-week total treatment period |
| BG001 | Olanzapine | Olanzapine, 5 mg BID on Day 1 to 7, and 15 mg (5 mg in the morning and 10 mg in the evening) thereafter for a 4-week total treatment period |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) at Week 4 | PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. PANSS measure is composed of 3 scales: Positive scale, Negative scale, and General Psychopathology scale. Positive scale assesses hallucinations, delusions and related symptoms; Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms; and General Psychopathology scale addresses other symptoms such as anxiety, somatic concern and disorientation. The PANSS has 30 items in its 3 scales and an anchored Likert scale from 1 to 7 is used to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. The Positive scale has 7 items with a score from 7 to 49, the Negative scale has 7 items with a score from 7 to 49, and the General Psychopathology scale has 16 items with a score from 16 to 112. A total score is the sum of the 3 scores for the 3 scales. | Randomized participants with any PANSS measurements between Baseline and Week 4. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Week 4 |
Up to 6 Weeks
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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 | MK-8998 | MK-8998, 6 mg twice a day (BID) on Days 1 to 7, and 8 mg BID thereafter for a 4-week total treatment period |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Erysipelas | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| Comparator: Olanzapine | Drug | Olanzapine 5 mg tablets twice daily with food on Days 1 through 7. On Day 8, dosage will be increased to 5 mg tablets in the morning and 10 mg tablets in the evening. Treatment period is 4 weeks. There will be a period of time when all participants will receive placebo. |
|
| Comparator: Placebo | Drug | Placebo tablets matching olanzapine tablets and MK-8998 capsules |
|
| Week 4 |
| Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) at Week 4 | CGI-S is a commonly used measure of symptom severity in treatment studies of participants with mental disorders. CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = extremely ill. | Baseline and Week 4 |
| Mean Change From Baseline in PANSS Positive Subscale at Week 4 | PANSS Positive scale assesses hallucinations, delusions and related symptoms. The Positive scale has 7 items with an anchored Likert scale from 1 to 7 to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. A total score ranges from 7 to 49. | Baseline and Week 4 |
| Mean Change From Baseline in PANSS Negative Subscale at Week 4 | PANSS Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms. The Negative scale has 7 items with an anchored Likert scale from 1 to 7 to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. A total score ranges from 7 to 49. | Baseline and Week 4 |
| Physician Decision |
|
| Pregnancy |
|
| Progressive Disease |
|
| Protocol Violation |
|
| Withdrawal by Subject |
|
| BG002 | Placebo Comparator | Placebo Comparator to MK-8998 or olanzapine |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | MK-8998 | MK-8998, 6 mg twice a day (BID) on Days 1 to 7, and 8 mg BID thereafter for a 4-week total treatment period |
| OG001 | Olanzapine | Olanzapine, 5 mg BID on Day 1 to 7, and 15 mg (5 mg in the morning and 10 mg in the evening) thereafter for a 4-week total treatment period |
| OG002 | Placebo Comparator | Placebo Comparator to MK-8998 or olanzapine |
|
|
|
| Primary | Number of Participants Who Experienced at Least One Adverse Event | An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug. | All participants included in the All Patients as Treated (APaT) population received at least one dose of study treatment and were evaluated for safety. | Posted | Number | Participants | Up to 6 Weeks |
|
|
|
| Primary | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug. | All participants included in the All Patients as Treated (APaT) population received at least one dose of study treatment and were evaluated for safety. | Posted | Number | Participants | Up to 4 Weeks |
|
|
|
| Secondary | Percentage of Participants With Response at Week 4 | Responders were defined as participants who demonstrated ≥ 20% improvement from baseline on the PANSS total score. PANSS measure is composed of 3 scales: Positive scale, Negative scale, and General Psychopathology scale. Positive scale assesses hallucinations, delusions and related symptoms; Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms; and General Psychopathology scale addresses other symptoms such as anxiety, somatic concern and disorientation. The PANSS has 30 items in its 3 scales and an anchored Likert scale from 1 to 7 is used to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. The Positive scale has 7 items with a score from 7 to 49, the Negative scale has 7 items with a score from 7 to 49, and the General Psychopathology scale has 16 items with a score from 16 to 112. A total score is the sum of the 3 scores for the 3 scales. | Randomized participants with a PANSS measurement at Week 4. | Posted | Number | Percentage of participants | Week 4 |
|
|
|
|
| Secondary | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) at Week 4 | CGI-S is a commonly used measure of symptom severity in treatment studies of participants with mental disorders. CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = extremely ill. | Randomized participants with any CGI-S measurements between baseline and Week 4. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Week 4 |
|
|
|
|
| Secondary | Mean Change From Baseline in PANSS Positive Subscale at Week 4 | PANSS Positive scale assesses hallucinations, delusions and related symptoms. The Positive scale has 7 items with an anchored Likert scale from 1 to 7 to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. A total score ranges from 7 to 49. | Randomized participants with any PANSS positive subscale measurements between baseline and Week 4. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Week 4 |
|
|
|
|
| Secondary | Mean Change From Baseline in PANSS Negative Subscale at Week 4 | PANSS Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms. The Negative scale has 7 items with an anchored Likert scale from 1 to 7 to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. A total score ranges from 7 to 49. | Randomized participants with any PANSS negative subscale measurements between baseline and Week 4. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Week 4 |
|
|
|
|
| 0 |
| 86 |
| 19 |
| 86 |
| EG001 | Olanzapine | Olanzapine, 5 mg BID on Day 1 to 7, and 15 mg (5 mg in the morning and 10 mg in the evening) thereafter for a 4-week total treatment period | 0 | 47 | 14 | 47 |
| EG002 | Placebo Comparator | Placebo Comparator to MK-8998 or olanzapine | 1 | 83 | 11 | 83 |
| Somnolence | Nervous system disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | Systematic Assessment |
|
The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
| Odds Ratio (OR) |
| 2.20 |
| 2-Sided |
| 95 |
| 0.95 |
| 5.09 |
| No |
| Superiority or Other |
| Mean Difference (Final Values) |
| 0.0 |
| 2-Sided |
| 95 |
| -0.4 |
| 0.4 |
| No |
| Superiority or Other |
| Mean Difference (Final Values) |
| -1.3 |
| 2-Sided |
| 95 |
| -3.6 |
| 0.9 |
| No |
| Superiority or Other |
| Mean Difference (Final Values) |
| -0.2 |
| 2-Sided |
| 95 |
| -2.0 |
| 1.6 |
| No |
| Superiority or Other |