SchizophreniaPhase 1MDCSNCT03565068
A Safety, Tolerability, and Pharmacokinetics Study of MK-8189 in Participants With Schizophrenia and in Healthy Participants (MK-8189-007)
A Phase 1 study testing MK-8189 and Background AAP Therapy in people with Schizophrenia, run by Merck Sharp & Dohme LLC at 1 site in United States.
Trial summary
This 4-panel study will evaluate the safety, tolerability, pharmacokinetics (PK) and corrected QT interval (QTc) effect of MK-8189 versus placebo, as monotherapy in healthy participants (Panel A) including those of Japanese descent, as monotherapy in participants with schizophrenia (Panel B), as add-on therapy in… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- MK-8189 and Background AAP Therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2018to 3 Apr 2020
- Phase
- Phase 1
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Panel A (Healthy Participants)
- If participant is of Japanese descent, both biological parents and all biological grandparents must be born in Japan.
- Panels B and D (Participants with Schizophrenia; MK-8189 or Placebo Monotherapy / 15-Day Titration Monotherapy) - Is able to discontinue the use of all antipsychotic medication at least 5 days prior to the start of the treatment period and during the study period.
- Panels B, C, and D (Participants with Schizophrenia; MK-8189 or Placebo Monotherapy / Add-on Therapy / 15-Day Titration Monotherapy)
- Meets diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria with the onset of the first episode being no less than 2 years prior to screening and monotherapy with antipsychotics for treatment should be indicated.
- Is in the non-acute phase of their illness and clinically stable for 3 months prior to screening as demonstrated by: a.) no clinically significant change in dose of prescribed antipsychotic medication, or clinically significant change in antipsychotic medication to treat symptoms of schizophrenia for 2 months prior to screening; b.) no increase in level of psychiatric care due to worsening of symptoms of schizophrenia for 3 months prior to screening.
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- Has a history of receiving and tolerating antipsychotic medication within the usual dose range employed for schizophrenia.
- Has a stable living situation in which the participant or a contact person can be reached by the investigator if there is a need for follow up.
- Participants with hypothyroidism, diabetes, high blood pressure, chronic respiratory conditions or other mild forms of these medical conditions could be considered as candidates for study enrollment if their condition is stable and the prescribed dose and regimen of medication is stable for at least 3 months prior to screening and there are no expected changes in co-medication during the study.
- Has regular bowel movements.
- Panels A, B, C, and D
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP)
- Is a WOCBP and using a contraceptive method that is highly effective, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 14 days after the last dose of study intervention.
Who cannot join
- Panel A (Healthy Participants)
- Has a history of clinically diagnosed depression, anxiety disorder, or any history of psychiatric disorders having required drug treatment or hospitalization. Participants who have had situational depression more than 5 years before the start of the study may be enrolled in the study at the discretion of the investigator.
- Has a history of stroke, chronic seizures, or major neurological disorder.
- Has a history of dystonic reaction to antipsychotic, anti-emetic or related medication.
- Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia Suicide Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator. Participants must be excluded if they report suicidal ideation with intent, with or without a plan or method (e.g., positive response to item 4 or 5 in assessment of suicidal ideation on the C-SSRS) in the past 5 years or suicidal behavior in their lifetime.
- Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a remote history of uncomplicated medical events may be enrolled in the study at the discretion of the investigator.
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- Is mentally or legally incapacitated, has a history of clinically significant psychiatric disorder of the last 5 years. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator.
- Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies, beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods), until the poststudy visit.
- Is a smoker and/or has used nicotine or nicotine-containing products (e.g., nicotine patch and electronic cigarette) within 3 months of screening.
- Panels B, C, and D (Participants with Schizophrenia; MK-8189 or Placebo Monotherapy / Add-on Therapy / 15-Day Titration Monotherapy)
- Has evidence or history of a primary DSM-5 axis I psychiatric diagnosis other than schizophrenia or schizoaffective disorder per the allowed DSM-5 criteria within 1 month of screening.
- Has evidence or history of mental retardation, borderline personality disorder, anxiety disorder, or organic brain syndrome.
- Has a history of neuroleptic malignant syndrome or moderate to severe tardive dyskinesia (TD).
- Has a substance-induced psychotic disorder or behavioral disturbance thought to be due to substance abuse.
- Has a DSM-5 defined substance abuse or dependence disorder (excluding nicotine and caffeine) within three months of screening.
- Has a history of seizure disorder beyond childhood or is receiving treatment with any anticonvulsant to prevent seizures.
- Is at imminent risk of self-harm, based on clinical interview and responses on the C-SSRS, or of harm to others in the opinion of the investigator. Participants must be excluded if they report suicidal ideation with intent, with or without a plan or method (e.g., positive response to item 4 or 5 in assessment of suicidal ideation on the C-SSRS) in the past 2 months or suicidal behavior in the past 6 months.
- Has received treatment with clozapine for schizophrenia or treatment with monoamine oxidase inhibitors within 3 months of screening. For Panel C participants, has received a total daily dose of risperidone > 6 mg.
- Is unable to refrain from the use of co-medication with a moderate or strong inhibiting or inducing effect on cytochrome P450 (CYP) 3A (CYP3A) and/or CYP2C9 beginning approximately 2 weeks or 5 half- lives, whichever is longer, prior to administration of the initial dose of trial drug and throughout the trial or is unable to refrain from the use of sensitive substrates of CYP2B6. Unable to refrain from cyclic hormone replacement therapy. There may be certain medications that are permitted
- Has received a parenteral depot antipsychotic medication within 3 months of pre-trial (screening).
- Panels A, B, C, and D
- Is a woman of childbearing potential (WOCBP) who has a positive serum pregnancy test at the screening visit or a positive urine pregnancy test within 48 hours before the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has a history of cancer (malignancy). Exceptions include: (1) Participants with adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix may participate in the study; (2) Participants with other malignancies which have been successfully treated ≥10 years prior to the prestudy (screening) visit where, in the judgment of both the investigator and treating physician, appropriate follow-up has revealed no evidence of recurrence from the time of treatment through the time of the prestudy (screening) visit (except those cancers identified at the beginning of this exclusion criteria); or (3) Participants, who, in the opinion of the study investigator, are highly unlikely to sustain a recurrence for the duration of the study.
- Has a clinically significant history or presence of sick sinus syndrome, first, second, or third degree atrioventricular (AV) block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged QTc interval, or conduction abnormalities.
- Has history of repeated or frequent syncope, vasovagal episodes, or epileptic seizures.
- Has a family history of sudden death.
- Has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
- Has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e., systemic allergic reaction) to prescription or non-prescription drugs or food.
- Has Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV) infection.
- Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
- Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit. The window will be derived from the date of the last visit in the previous study.
- Has history or presence of risk factors for Torsade de Pointes (e.g., cardiac disease, heart failure, hypokalaemia or hypomagnesaemia, hypertrophy, cardiomyopathy, or family history of long QT syndrome). Plasma calcium must be within normal limits at screening and serum calcium must be within normal limits prior to dosing.
- Is under the age of legal consent.
- Has been in incarceration or imprisonment within 3 months prior to screening.
- Consumes greater than 3 glasses of alcoholic beverages per day. Participants who consume 4 glasses of alcoholic beverages per day may be enrolled at the discretion of the investigator.
- Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
- Is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 years.
Trial locations and contacts
1 site in 1 country.
United States1 site
California Clinical Trials ( Site 0001)
Glendale, California, 91206
About this study
Official title: A Multiple-dose Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and QTc Effect of MK-8189 in Participants With Schizophrenia and Healthy Participants.
This 4-panel study will evaluate the safety, tolerability, pharmacokinetics (PK) and corrected QT interval (QTc) effect of MK-8189 versus placebo, as monotherapy in healthy participants (Panel A) including those of Japanese descent, as monotherapy in participants with schizophrenia (Panel B), as add-on therapy in participants with schizophrenia (Panel C), and under an alternative dosing regimen as monotherapy in participants with schizophrenia (Panel D). Analysis of QTc effect will be exploratory. There will be no hypothesis testing in this study.
Read the detailed description
As specified by Phase 1 protocol-flexible language in the protocol, modifications to the dose or dosing regimen can be made to achieve the scientific goals of the study objectives and/or to ensure appropriate safety of the study participants. The proposed doses for each Panel may be adjusted downward based on evaluation of observed safety, tolerability, and PK data.
- Conditions
- Schizophrenia
- Being tested
- MK-8189, Placebo, Background AAP Therapy
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-8189Drug
MK-8189 4 mg tablet(s) will be administered orally QD for a total daily dose of 4 mg, 8 mg, 12 mg, 16 mg, 20 mg, 24 mg, 36 mg or 48 mg.
PlaceboDrug
MK-8189 dose-matching placebo tablets will be administered orally QD.
Background AAP TherapyDrug
Participants with schizophrenia in Panel C will be on background therapy with an AAP medication (e.g., olanzapine, quetiapine, paliperidone, asenapine, iloperidone, aripirprazole, lurasidone, risperidone [not to exceed daily dose of 6 mg], or ziprasidone) throughout the study. Participants should be on a stable and well tolerated treatment regimen for at least 2 months prior to screening. NOTE: clozapine is not allowed.
| Study group | Role | What they receive |
|---|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 4-24 mg | Experimental | Healthy participants will receive MK-8189 monotherapy orally once daily (QD) in escalating doses from 4 mg to 24 mg, as follows: Days 1-3: 4 mg, Days 4-6: 8 mg, Days 7-9: 12 mg, Days 10-12: 16 mg, Days 13-15: 20 mg, Days 16-18: 24 mg, depending on safety and tolerability. Receives: Drug: MK-8189 |
| Panel A (Healthy Participants): Placebo Monotherapy | Placebo comparator | Healthy participants will receive MK-8189 monotherapy matching placebo orally QD on Days 1-18. Receives: Drug: Placebo |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 4-24 mg | Experimental | Participants with Schizophrenia will receive MK-8189 monotherapy orally QD in escalating doses from 4 mg to 24 mg, as follows: Days 1-3: 4 mg, Days 4-6: 8 mg, Days 7-9: 12 mg, Days 10-12: 16 mg, Days 13-15: 20 mg, Days 16-18: 24 mg, depending on safety and tolerability. Receives: Drug: MK-8189 |
| Panel B (Schizophrenia Participants): Placebo Monotherapy | Placebo comparator | Participants with Schizophrenia will receive MK-8189 monotherapy matching placebo orally QD on Days 1-18. Receives: Drug: Placebo |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 4-24 mg | Experimental | In addition to background atypical antipsychotic (AAP) treatment, participants with Schizophrenia will receive MK-8189 add-on therapy orally QD in escalating doses from 4 mg to 24 mg, as follows: Days 1-3: 4 mg, Days 4-6: 8 mg, Days 7-9: 12 mg, Days 10-12: 16 mg, Days 13-15: 20 mg, Days 16-18: 24 mg, depending on safety and tolerability. Receives: Drug: MK-8189; Drug: Background AAP Therapy |
| Panel C (Schizophrenia Participants): Placebo Add-on Therapy | Placebo comparator | In addition to background AAP treatment, participants with Schizophrenia will receive MK-8189 add-on therapy matching placebo orally QD on Days 1-18. Receives: Drug: Placebo; Drug: Background AAP Therapy |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 8-48 mg | Experimental | Participants with Schizophrenia will receive MK-8189 monotherapy orally QD in escalating doses from 8 mg to 48 mg, as follows: Days 1-3: 8 mg, Days 4-6: 16 mg, Days 7-9: 24 mg, Days 10-12: 36 mg, Days 13-15: 48 mg, depending on safety and tolerability. Receives: Drug: MK-8189 |
| Panel D (Schizophrenia Participants): Placebo Monotherapy | Placebo comparator | Participants with Schizophrenia will receive MK-8189 monotherapy matching placebo orally QD on Days 1-15. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants Who Experienced One or More Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Per protocol, safety was analyzed by panel and dose. The number of participants who experienced one or more AEs was reported.
Measured: Up to ~32 days
The Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Per protocol, safety was analyzed by panel and dose. The number of participants who discontinued study treatment due to an AE was reported.
Measured: Up to ~18 days
Secondary outcomes (7)
Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189
AUC was a measure of MK-8189 exposure assessed as a product of drug concentration and time, using a linear mixed effects model. To estimate AUC0-24hr per protocol blood samples were collected pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose for Panels A, B, C, D; no pre-dose samples collected on Day 18 (Panels A, B, C), Day 15 (Panel D). Samples were collected on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol AUC0-24hr was analyzed by panel, dose, dosing regimen; due to differing dosing regimen some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of AUC0-24hr analysis and these arms were excluded. Geometric coefficient of variation (GCV) was reported as a percent. Per protocol placebo arms were excluded from AUC0-24hr analysis.
Measured: Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D); Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D: Days 1, 4, 7, 10, 13, 15
Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189
Cmax was the maximum concentration of MK-8189 observed in plasma, assessed using a linear mixed effects model. To estimate Cmax, per protocol blood samples were collected pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose for Panels A, B, C, D; no pre-dose samples collected on Day 18 (Panels A, B, C), Day 15 (Panel D); additional post-dose samples collected at 36, 48 hours on Days 18 and 15. Samples were collected on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol Cmax was analyzed by panel, dose, dosing regimen; due to differing dosing regimen some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of Cmax analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from Cmax analysis.
Measured: Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D);additional 36, 48 hours post-dose on Days 18, 15; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D:Days 1, 4, 7, 10, 13, 15
Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189
C24hr was the concentration of MK-8189 observed in plasma at the 24-hour nominal sampling time after administration of MK-8189, assessed using a linear mixed effects model. To estimate C24hr, per protocol blood samples were collected 24 hours post-dose on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol C24hr was analyzed by panel, dose, dosing regimen; due to differing dosing regimen some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of C24hr analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from C24hr analysis.
Measured: 24 hours post-dose; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D: Days 1, 4, 7, 10, 13, 15
Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189
Tmax was the actual sampling time at which maximum post-dose plasma concentration of MK-8189 was observed. To estimate Tmax, per protocol blood samples were collected pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose for Panels A, B, C, D; no pre-dose samples collected on Day 18 (Panels A, B, C), Day 15 (Panel D); additional post-dose samples collected at 36, 48 hours on Days 18 and 15. Samples were collected on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol Tmax was analyzed by panel, dose, dosing regimen; due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of Tmax analysis and were excluded. Per protocol placebo arms were excluded from Tmax analysis.
Measured: Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D);additional 36, 48 hours post-dose on Days 18, 15; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D:Days 1, 4, 7, 10, 13, 15
Apparent Total Plasma Clearance of MK-8189 (CL/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D)
CL/F was the apparent total clearance of MK-8189 in plasma over time, assessed as the rate at which MK-8189 was removed from the plasma. To estimate CL/F, per protocol blood samples were collected 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 for Panels A, B, C, and on Day 15 for Panel D. Per protocol CL/F was analyzed by panel, dose and dosing regimen. Due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) study arms weren't applicable to the protocol-specified timepoints/days of CL/F analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from CL/F analysis.
Measured: 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D)
Apparent Volume of MK-8189 Distribution (Vd/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D)
Vd/F was the apparent volume of distribution of MK-8189 between the plasma and the rest of the body, after dose, assessed as the total volume of MK-8189 that would need to be uniformly distributed to achieve the desired plasma drug concentration. To estimate Vd/F, per protocol blood samples were collected 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 for Panels A, B, C, and on Day 15 for Panel D. Per protocol Vd/F was analyzed by panel, dose and dosing regimen. Due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) study arms weren't applicable to the protocol-specified timepoints/days of Vd/F analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from Vd/F analysis.
Measured: 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D)
Time Required for Plasma Concentration of MK-8189 to Decrease by Half (Apparent Terminal Half-life [t1/2]) on Day 18 (Panels A, B, C) and Day 15 (Panel D)
t1/2 was the time required to divide the plasma concentration of MK-8189 by half after reaching pseudo-equilibrium. At least three quantifiable terminal phase concentrations collected were used to calculate t1/2. To estimate t1/2, per protocol blood samples were collected 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 for Panels A, B, C, and on Day 15 for Panel D. Per protocol t1/2 was analyzed by panel, dose and dosing regimen. Due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) study arms weren't applicable to the protocol-specified timepoints/days of t1/2 analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from t1/2 analysis.
Measured: 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2018
- Study start20 Jun 2018
- Primary completion3 Apr 2020
- Study completion3 Apr 2020
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 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 75 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
- NCT03565068
- Sponsor's protocol ID
- 8189-007
- Other IDs
- MK-8189-007
- Acronym
- MDCS
- Status last verified
- Mar 2021
- First submitted
- 1 Jun 2018
- Last updated
- 29 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multiple-dose Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and QTc Effect of MK-8189 in Participants With Schizophrenia and Healthy Participants.
- ClinicalTrials.gov ID
- NCT03565068
- Acronym / sponsor ID
- MDCS / 8189-007
- Conditions
- Schizophrenia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 20 Jun 2018 (actual)
- Primary completion
- 3 Apr 2020 (actual)
- Study completion
- 3 Apr 2020 (actual)
- First posted
- 21 Jun 2018 (actual)
- Results
- Posted 29 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 4-panel study will evaluate the safety, tolerability, pharmacokinetics (PK) and corrected QT interval (QTc) effect of MK-8189 versus placebo, as monotherapy in healthy participants (Panel A) including those of Japanese descent, as monotherapy in participants with schizophrenia (Panel B), as add-on therapy in participants with schizophrenia (Panel C), and under an alternative dosing regimen as monotherapy in participants with schizophrenia (Panel D). Analysis of QTc effect will be exploratory. There will be no hypothesis testing in this study.
Detailed description
As specified by Phase 1 protocol-flexible language in the protocol, modifications to the dose or dosing regimen can be made to achieve the scientific goals of the study objectives and/or to ensure appropriate safety of the study participants. The proposed doses for each Panel may be adjusted downward based on evaluation of observed safety, tolerability, and PK data.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 4-24 mg | Experimental | Drug: MK-8189Healthy participants will receive MK-8189 monotherapy orally once daily (QD) in escalating doses from 4 mg to 24 mg, as follows: Days 1-3: 4 mg, Days 4-6: 8 mg, Days 7-9: 12 mg, Days 10-12: 16 mg, Days 13-15: 20 mg, Days 16-18: 24 mg, depending on safety and tolerability. |
| Panel A (Healthy Participants): Placebo Monotherapy | Placebo comparator | Drug: PlaceboHealthy participants will receive MK-8189 monotherapy matching placebo orally QD on Days 1-18. |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 4-24 mg | Experimental | Drug: MK-8189Participants with Schizophrenia will receive MK-8189 monotherapy orally QD in escalating doses from 4 mg to 24 mg, as follows: Days 1-3: 4 mg, Days 4-6: 8 mg, Days 7-9: 12 mg, Days 10-12: 16 mg, Days 13-15: 20 mg, Days 16-18: 24 mg, depending on safety and tolerability. |
| Panel B (Schizophrenia Participants): Placebo Monotherapy | Placebo comparator | Drug: PlaceboParticipants with Schizophrenia will receive MK-8189 monotherapy matching placebo orally QD on Days 1-18. |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 4-24 mg | Experimental | Drug: MK-8189, Drug: Background AAP TherapyIn addition to background atypical antipsychotic (AAP) treatment, participants with Schizophrenia will receive MK-8189 add-on therapy orally QD in escalating doses from 4 mg to 24 mg, as follows: Days 1-3: 4 mg, Days 4-6: 8 mg, Days 7-9: 12 mg, Days 10-12: 16 mg, Days 13-15: 20 mg, Days 16-18: 24 mg, depending on safety and tolerability. |
| Panel C (Schizophrenia Participants): Placebo Add-on Therapy | Placebo comparator | Drug: Placebo, Drug: Background AAP TherapyIn addition to background AAP treatment, participants with Schizophrenia will receive MK-8189 add-on therapy matching placebo orally QD on Days 1-18. |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 8-48 mg | Experimental | Drug: MK-8189Participants with Schizophrenia will receive MK-8189 monotherapy orally QD in escalating doses from 8 mg to 48 mg, as follows: Days 1-3: 8 mg, Days 4-6: 16 mg, Days 7-9: 24 mg, Days 10-12: 36 mg, Days 13-15: 48 mg, depending on safety and tolerability. |
| Panel D (Schizophrenia Participants): Placebo Monotherapy | Placebo comparator | Drug: PlaceboParticipants with Schizophrenia will receive MK-8189 monotherapy matching placebo orally QD on Days 1-15. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Panel A (Healthy Participants)
- If participant is of Japanese descent, both biological parents and all biological grandparents must be born in Japan.
- Panels B and D (Participants with Schizophrenia; MK-8189 or Placebo Monotherapy / 15-Day Titration Monotherapy) - Is able to discontinue the use of all antipsychotic medication at least 5 days prior to the start of the treatment period and during the study period.
- Panels B, C, and D (Participants with Schizophrenia; MK-8189 or Placebo Monotherapy / Add-on Therapy / 15-Day Titration Monotherapy)
- Meets diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria with the onset of the first episode being no less than 2 years prior to screening and monotherapy with antipsychotics for treatment should be indicated.
Key exclusion criteria (37 listed)
- Panel A (Healthy Participants)
- Has a history of clinically diagnosed depression, anxiety disorder, or any history of psychiatric disorders having required drug treatment or hospitalization. Participants who have had situational depression more than 5 years before the start of the study may be enrolled in the study at the discretion of the investigator.
- Has a history of stroke, chronic seizures, or major neurological disorder.
- Has a history of dystonic reaction to antipsychotic, anti-emetic or related medication.
- Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia Suicide Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator. Participants must be excluded if they report suicidal ideation with intent, with or without a plan or method (e.g., positive response to item 4 or 5 in assessment of suicidal ideation on the C-SSRS) in the past 5 years or suicidal behavior in their lifetime.
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-8189MK-8189 4 mg tablet(s) will be administered orally QD for a total daily dose of 4 mg, 8 mg, 12 mg, 16 mg, 20 mg, 24 mg, 36 mg or 48 mg. | Drug | Panel A (Healthy Participants): MK-8189 Monotherapy 4-24 mg, Panel B (Schizophrenia Participants): MK-8189 Monotherapy 4-24 mg, Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 4-24 mg, Panel D (Schizophrenia Participants): MK-8189 Monotherapy 8-48 mg |
| PlaceboMK-8189 dose-matching placebo tablets will be administered orally QD. | Drug | Panel A (Healthy Participants): Placebo Monotherapy, Panel B (Schizophrenia Participants): Placebo Monotherapy, Panel C (Schizophrenia Participants): Placebo Add-on Therapy, Panel D (Schizophrenia Participants): Placebo Monotherapy |
| Background AAP TherapyParticipants with schizophrenia in Panel C will be on background therapy with an AAP medication (e.g., olanzapine, quetiapine, paliperidone, asenapine, iloperidone, aripirprazole, lurasidone, risperidone [not to exceed daily dose of 6 mg], or ziprasidone) throughout the study. Participants should be on a stable and well tolerated treatment regimen for at least 2 months prior to screening. NOTE: clozapine is not allowed. | Drug | Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 4-24 mg, Panel C (Schizophrenia Participants): Placebo Add-on Therapy |
Primary outcome
The Number of Participants Who Experienced One or More Adverse Events (AEs)
Time frame: Up to ~32 days
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Per protocol, safety was analyzed by panel and dose. The number of participants who experienced one or more AEs was reported.
The Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: Up to ~18 days
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Per protocol, safety was analyzed by panel and dose. The number of participants who discontinued study treatment due to an AE was reported.
7 secondary outcomes
Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189
Time frame: Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D); Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D: Days 1, 4, 7, 10, 13, 15
Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189
Time frame: Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D);additional 36, 48 hours post-dose on Days 18, 15; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D:Days 1, 4, 7, 10, 13, 15
Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189
Time frame: 24 hours post-dose; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D: Days 1, 4, 7, 10, 13, 15
Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189
Time frame: Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D);additional 36, 48 hours post-dose on Days 18, 15; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D:Days 1, 4, 7, 10, 13, 15
Apparent Total Plasma Clearance of MK-8189 (CL/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D)
Time frame: 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D)
Apparent Volume of MK-8189 Distribution (Vd/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D)
Time frame: 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D)
Time Required for Plasma Concentration of MK-8189 to Decrease by Half (Apparent Terminal Half-life [t1/2]) on Day 18 (Panels A, B, C) and Day 15 (Panel D)
Time frame: 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-8189 and Background AAP Therapy in people with Schizophrenia, run by Merck Sharp & Dohme LLC at 1 site in United States.
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 14 inclusion and 37 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 29 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 29 Mar 2021). 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?
The Number of Participants Who Experienced One or More Adverse Events (AEs) (time frame: Up to ~32 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 29 Mar 2021.