Trial Outcomes & Findings for A Study to Test the Safety and Efficacy of MK-8998 in Acutely Psychotic Participants With Schizophrenia (MK-8998-004) (NCT NCT00827918)

NCT ID: NCT00827918

Last Updated: 2015-10-21

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 216 participants
• Primary outcome timeframe: Baseline and Week 4
• Results posted on: 2015-10-21

Participant Flow

Male and female inpatients who were experiencing an acute exacerbation of schizophrenia were randomized at 21 sites worldwide.

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.

Participant milestones

Measure	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	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	Placebo Comparator Placebo Comparator to MK-8998 or olanzapine
Overall Study STARTED	86	47	83
Overall Study COMPLETED	58	38	62
Overall Study NOT COMPLETED	28	9	21

Reasons for withdrawal

Measure	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	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	Placebo Comparator Placebo Comparator to MK-8998 or olanzapine
Overall Study Adverse Event	4	0	0
Overall Study Lack of Efficacy	16	4	15
Overall Study Physician Decision	1	0	0
Overall Study Pregnancy	0	1	0
Overall Study Progressive Disease	1	1	0
Overall Study Protocol Violation	0	1	0
Overall Study Withdrawal by Subject	6	2	6

Baseline Characteristics

A Study to Test the Safety and Efficacy of MK-8998 in Acutely Psychotic Participants With Schizophrenia (MK-8998-004)

Baseline characteristics by cohort

Measure	MK-8998 n=86 Participants 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	Olanzapine n=47 Participants 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	Placebo Comparator n=83 Participants Placebo Comparator to MK-8998 or olanzapine	Total n=216 Participants Total of all reporting groups
Age, Continuous	37.4 years n=5 Participants	36.1 years n=7 Participants	36.4 years n=5 Participants	36.8 years n=4 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	23 Participants n=7 Participants	30 Participants n=5 Participants	90 Participants n=4 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	24 Participants n=7 Participants	53 Participants n=5 Participants	126 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: Randomized participants with any PANSS measurements between Baseline and 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.

Outcome measures

Measure	MK-8998 n=81 Participants 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	Olanzapine n=45 Participants 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	Placebo Comparator n=78 Participants Placebo Comparator to MK-8998 or olanzapine
Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) at Week 4	-13.3 Units on a scale Interval -17.9 to -8.7	-17.0 Units on a scale Interval -22.8 to -11.1	-12.7 Units on a scale Interval -17.2 to -8.2

PRIMARY outcome

Timeframe: Up to 6 Weeks

Population: All participants included in the All Patients as Treated (APaT) population received at least one dose of study treatment and were evaluated for safety.

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.

Outcome measures

Measure	MK-8998 n=86 Participants 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	Olanzapine n=47 Participants 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	Placebo Comparator n=83 Participants Placebo Comparator to MK-8998 or olanzapine
Number of Participants Who Experienced at Least One Adverse Event	41 Participants	23 Participants	33 Participants

PRIMARY outcome

Timeframe: Up to 4 Weeks

Population: All participants included in the All Patients as Treated (APaT) population received at least one dose of study treatment and were evaluated for safety.

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.

Outcome measures

Measure	MK-8998 n=86 Participants 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	Olanzapine n=47 Participants 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	Placebo Comparator n=83 Participants Placebo Comparator to MK-8998 or olanzapine
Number of Participants Who Discontinued Study Drug Due to an Adverse Event	9 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Week 4

Population: Randomized participants with a PANSS measurement 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.

Outcome measures

Measure	MK-8998 n=54 Participants 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	Olanzapine n=36 Participants 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	Placebo Comparator n=58 Participants Placebo Comparator to MK-8998 or olanzapine
Percentage of Participants With Response at Week 4	57.4 Percentage of participants	66.7 Percentage of participants	48.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Randomized participants with any CGI-S measurements between baseline and 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.

Outcome measures

Measure	MK-8998 n=81 Participants 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	Olanzapine n=45 Participants 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	Placebo Comparator n=78 Participants Placebo Comparator to MK-8998 or olanzapine
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) at Week 4	-0.9 Units on a scale Interval -1.2 to -0.7	-0.8 Units on a scale Interval -1.2 to -0.5	-0.9 Units on a scale Interval -1.1 to -0.6

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Randomized participants with any PANSS positive subscale measurements between baseline and 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.

Outcome measures

Measure	MK-8998 n=81 Participants 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	Olanzapine n=45 Participants 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	Placebo Comparator n=78 Participants Placebo Comparator to MK-8998 or olanzapine
Mean Change From Baseline in PANSS Positive Subscale at Week 4	-4.2 Units on a scale Interval -5.6 to -2.8	-5.6 Units on a scale Interval -7.4 to -3.8	-4.2 Units on a scale Interval -5.6 to -2.9

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Randomized participants with any PANSS negative subscale measurements between baseline and 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.

Outcome measures

Measure	MK-8998 n=81 Participants 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	Olanzapine n=45 Participants 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	Placebo Comparator n=78 Participants Placebo Comparator to MK-8998 or olanzapine
Mean Change From Baseline in PANSS Negative Subscale at Week 4	-3.3 Units on a scale Interval -4.5 to -2.2	-3.1 Units on a scale Interval -4.5 to -1.6	-2.9 Units on a scale Interval -4.0 to -1.8

Adverse Events

MK-8998

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Olanzapine

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo Comparator

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	MK-8998 n=86 participants at risk 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	Olanzapine n=47 participants at risk 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	Placebo Comparator n=83 participants at risk Placebo Comparator to MK-8998 or olanzapine
Infections and infestations Erysipelas	0.00% 0/86 • Up to 6 Weeks	0.00% 0/47 • Up to 6 Weeks	1.2% 1/83 • Number of events 1 • Up to 6 Weeks

Other adverse events

Measure	MK-8998 n=86 participants at risk 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	Olanzapine n=47 participants at risk 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	Placebo Comparator n=83 participants at risk Placebo Comparator to MK-8998 or olanzapine
Nervous system disorders Headache	2.3% 2/86 • Number of events 3 • Up to 6 Weeks	6.4% 3/47 • Number of events 3 • Up to 6 Weeks	3.6% 3/83 • Number of events 4 • Up to 6 Weeks
Nervous system disorders Somnolence	2.3% 2/86 • Number of events 2 • Up to 6 Weeks	6.4% 3/47 • Number of events 8 • Up to 6 Weeks	1.2% 1/83 • Number of events 1 • Up to 6 Weeks
Psychiatric disorders Insomnia	15.1% 13/86 • Number of events 14 • Up to 6 Weeks	10.6% 5/47 • Number of events 6 • Up to 6 Weeks	8.4% 7/83 • Number of events 8 • Up to 6 Weeks
Cardiac disorders Sinus tachycardia	2.3% 2/86 • Number of events 2 • Up to 6 Weeks	6.4% 3/47 • Number of events 3 • Up to 6 Weeks	1.2% 1/83 • Number of events 1 • Up to 6 Weeks

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER