SchizophreniaPhase 2NCT00827918

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

A Phase 2 study testing MK-8998 and Comparator: Olanzapine in people with Schizophrenia, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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… Read more about this study

Who is it for?: Ages 18 to 55 years
Conditions the study is for: Schizophrenia
What is being tested?: MK-8998 and Comparator: Olanzapine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 216 participants
Where: No sites listed yet
Study dates: Mar 2009to Apr 2010
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 55 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Patient's age is 18 to 55
Patient meets DSM-IV/DSM-IV-TR criteria for a primary diagnosis of schizophrenia
The duration of the patients schizophrenia diagnosis must be greater than 1 year
Patient has an acute exacerbation of psychotic symptoms (of at least 3 days but no longer than 6 weeks) and marked deterioration of function

Who cannot join

Patient currently has a clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorder that would pose a risk to the patient in the opinion of the investigator if they were to participate in the study or that might confound the results of the study
The patient has evidence of acute hepatitis, clinically significant chronic hepatitis, or impaired hepatic function
The patient has a chronic organic disease of the central nervous system (other than schizophrenia) such as, tumors, inflammation, active seizure disorder, vascular disorder, Parkinson's disease, Alzheimer's disease or other forms of dementia, myasthenia gravis, or other degenerative processes. In addition, patients must not have a history of mental retardation or persistent neurological symptoms attributable to serious head injury
Patient has a history of alcohol/drug dependence within 3 months or alcohol/drug abuse within 1 month of screening. Exceptions include caffeine and nicotine abuse/dependence
Patient has a history of hypersensitivity to olanzapine OR poor response to olanzapine in the last 2 years OR intolerable side effects due to olanzapine OR patients current psychotic relapse occurred while consistently taking a therapeutic dose (10 mg or more) of olanzapine OR olanzapine is medically contradicted
Patient is refractory to antipsychotic treatment

About this study

Official title: A Phase IIa, Randomized, Multicenter, Double-Blind, Active Comparator- and Placebo-Controlled, Clinical Trial to Study the Safety and Efficacy of MK8998 in Acutely Psychotic Patients With Schizophrenia

Conditions: Schizophrenia
Being tested: MK-8998, Comparator: Olanzapine, Comparator: Placebo
Keywords: Acute Exacerbation of Schizophrenia
Medical subject headings: Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-8998Drug
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.
Comparator: OlanzapineDrug
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: PlaceboDrug
Placebo tablets matching olanzapine tablets and MK-8998 capsules

Study groups in NCT00827918
Study group	Role	What they receive
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 Receives: Drug: MK-8998
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 Receives: Drug: Comparator: Olanzapine
Placebo	Placebo comparator	Placebo Comparator to MK-8998 or olanzapine Receives: Drug: Comparator: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: Up to 4 Weeks

Secondary outcomes (4)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2009Apr 2010

First posted23 Jan 2009 (estimated)
Study startMar 2009
Primary completionApr 2010
Study completionApr 2010

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for SchizophreniaStudies 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: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 216 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00827918
Sponsor's protocol ID: 8998-004
Other IDs: 2009_519
Status last verified: Oct 2015
First submitted: 22 Jan 2009
Last updated: 21 Oct 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 23532746

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Schizophrenia trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase IIa, Randomized, Multicenter, Double-Blind, Active Comparator- and Placebo-Controlled, Clinical Trial to Study the Safety and Efficacy of MK8998 in Acutely Psychotic Patients With Schizophrenia
ClinicalTrials.gov ID: NCT00827918
Acronym / sponsor ID: 8998-004
Conditions: Schizophrenia
Keywords: Acute Exacerbation of Schizophrenia
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 216 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Mar 2009
Primary completion: Apr 2010 (actual)
Study completion: Apr 2010 (actual)
First posted: 23 Jan 2009 (estimated)
Results: Posted 6 Feb 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
MK-8998	Experimental	Drug: MK-8998MK-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	Drug: Comparator: OlanzapineOlanzapine, 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	Drug: Comparator: PlaceboPlacebo Comparator to MK-8998 or olanzapine

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Patient's age is 18 to 55
Patient meets DSM-IV/DSM-IV-TR criteria for a primary diagnosis of schizophrenia
The duration of the patients schizophrenia diagnosis must be greater than 1 year
Patient has an acute exacerbation of psychotic symptoms (of at least 3 days but no longer than 6 weeks) and marked deterioration of function

Key exclusion criteria (6 listed)

Patient currently has a clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorder that would pose a risk to the patient in the opinion of the investigator if they were to participate in the study or that might confound the results of the study
The patient has evidence of acute hepatitis, clinically significant chronic hepatitis, or impaired hepatic function
The patient has a chronic organic disease of the central nervous system (other than schizophrenia) such as, tumors, inflammation, active seizure disorder, vascular disorder, Parkinson's disease, Alzheimer's disease or other forms of dementia, myasthenia gravis, or other degenerative processes. In addition, patients must not have a history of mental retardation or persistent neurological symptoms attributable to serious head injury
Patient has a history of alcohol/drug dependence within 3 months or alcohol/drug abuse within 1 month of screening. Exceptions include caffeine and nicotine abuse/dependence
Patient has a history of hypersensitivity to olanzapine OR poor response to olanzapine in the last 2 years OR intolerable side effects due to olanzapine OR patients current psychotic relapse occurred while consistently taking a therapeutic dose (10 mg or more) of olanzapine OR olanzapine is medically contradicted

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
MK-8998MK-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.	Drug	MK-8998
Comparator: OlanzapineOlanzapine 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.	Drug	Olanzapine
Comparator: PlaceboPlacebo tablets matching olanzapine tablets and MK-8998 capsules	Drug	Placebo

Primary outcome

Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) at Week 4
Time frame: 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.
Number of Participants Who Experienced at Least One Adverse Event
Time frame: Up to 6 Weeks
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.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Time frame: Up to 4 Weeks
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.

4 secondary outcomes

Percentage of Participants With Response at Week 4
Time frame: Week 4
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) at Week 4
Time frame: Baseline and Week 4
Mean Change From Baseline in PANSS Positive Subscale at Week 4
Time frame: Baseline and Week 4
Mean Change From Baseline in PANSS Negative Subscale at Week 4
Time frame: Baseline and Week 4

Results and safety

Results posted to the registry on 6 Feb 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MK-8998	86	58
Olanzapine	47	38
Placebo Comparator	83	62

Primary outcome: Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) at Week 4

Time frame: Baseline and Week 4. Least squares mean (95% Confidence Interval). Unit: Units on a scale

Measure	MK-8998 n = 81	Olanzapine n = 45	Placebo Comparator n = 78
Value	-13.3 (-17.9 to -8.7)	-17.0 (-22.8 to -11.1)	-12.7 (-17.2 to -8.2)

MK-8998 vs Placebo Comparator: Mean Difference (Final Values): -0.6 (95% CI -7.0 to 5.8), p = 0.8590, Difference in the Least Squares Mean
Olanzapine vs Placebo Comparator: Mean Difference (Final Values): -4.3 (95% CI -11.7 to 3.1), p = 0.2534, Difference in the Least Squares Mean

Population analysed: Randomized participants with any PANSS measurements between Baseline and Week 4.

Primary outcome: Number of Participants Who Experienced at Least One Adverse Event

Time frame: Up to 6 Weeks. Number. Unit: Participants

Measure	MK-8998 n = 86	Olanzapine n = 47	Placebo Comparator n = 83
Value	41	23	33

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

Primary outcome: Number of Participants Who Discontinued Study Drug Due to an Adverse Event

Time frame: Up to 4 Weeks. Number. Unit: Participants

Measure	MK-8998 n = 86	Olanzapine n = 47	Placebo Comparator n = 83
Value	9	1	1

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

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 6 Weeks. Other adverse events reported at 5.0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MK-8998	0 of 86 (0%)	19 of 86 (22.1%)	Not reported
Olanzapine	0 of 47 (0%)	14 of 47 (29.8%)	Not reported
Placebo Comparator	1 of 83 (1.2%)	11 of 83 (13.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23532746Egan 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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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 Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MK-8998 and Comparator: Olanzapine in people with Schizophrenia, 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 4 inclusion and 6 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: finished, as of the sponsor's last update on 21 Oct 2015. 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 6 Feb 2014). 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?

Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) at Week 4 (time frame: Baseline and Week 4). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00827918, which also lists 1 linked publication.

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 21 Oct 2015.