Safety, Tolerability, and Pharmacokinetics Study of Elpipodect (MK-8189) in Participants With Schizophrenia and Healthy Participants (MK-8189-011)

NCT04506905 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 8189-011Merck Protocol Number
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 6

Brief Summary

This is a randomized, double-blind, 2-part clinical study of the safety, tolerability and pharmacokinetics of alternate elpipodect titration regimens. Part 1 assessed multiple dose once-daily titration regimens of elpipodect in young adult participants with schizophrenia. Part 2 assessed multiple once-daily doses of elpipodect in elderly participants with schizophrenia and healthy elderly participants.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (2)

• Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE)

  The number of participants with ≥1 AE is reported. An AE is 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.

  Up to approximately 27 days

• Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE

  The number of participants discontinuing from study treatment due to ≥1 AE is reported. An AE is 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.

  Up to approximately 27 days

Secondary Outcomes (14)

• Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours Postdose (AUC0-24) of MK-8189

  Days 1, 2, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose

• Part 1: Concentration 24 Hours Postdose (C24) of MK-8189

  Days 1, 2, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose

• Part 1: Maximum Plasma Concentration (Cmax) of MK-8189

  Days 1, 2, 3, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose

• Part 1: Time to Maximum Concentration (Tmax) of MK-8189

  Days 1, 2, 3, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose

• Part 1: Clearance (CL/F) of MK-8189

  Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose

Study Arms (9)

Part 1 (Panel A) Elpipodect

EXPERIMENTAL

Young adult participants with schizophrenia receive elpipodect titrated from 16 mg to 24 mg once daily (QD), orally, over a course of 7-day treatment.

Drug: Elpipodect

Part 1 (Panel B) Elpipodect

EXPERIMENTAL

Young adult participants with schizophrenia receive elpipodect titrated up to 24 mg QD, orally, over a course of 7-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panel.

Drug: Elpipodect

Part 1 (Panel C) Elpipodect

EXPERIMENTAL

Young adult participants with schizophrenia receive elpipodect titrated from 8 mg to 24 mg QD, orally, over a course of 7-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.

Drug: Elpipodect

Part 2 (Panel D) Elpipodect

EXPERIMENTAL

Elderly adult participants with schizophrenia receive elpipodect titrated from 8 mg to 24 mg QD, orally, over the course of a 13-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.

Drug: Elpipodect

Part 2 (Panel E) Elpipodect

EXPERIMENTAL

Elderly adult participants with schizophrenia receive elpipodect titrated from 16 mg to 24 mg QD, orally, over the course of 10-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.

Drug: Elpipodect

Part 2 (Panel F) Elpipodect

EXPERIMENTAL

Healthy elderly adult participants receive elpipodect titrated from 8 mg to 24 mg QD, orally, over the course of a 13-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.

Drug: Elpipodect

Part 2 (Panel G) Elpipodect

EXPERIMENTAL

Healthy elderly adult participants receive elpipodect titrated from 16 mg to 24 mg QD, orally, over the course of 10-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.

Drug: Elpipodect

Part 1 (Panels A, B, C) Placebo

PLACEBO COMPARATOR

Oral tablets of dose-matched placebo to total daily dose of elpipodect.

Drug: Placebo

Part 2 (Panels D, E, F, G) Placebo

PLACEBO COMPARATOR

Oral tablets of dose-matched placebo to total daily dose of elpipodect.

Drug: Placebo

Interventions

Placebo DRUG

Oral tablets of dose-matched placebo to MK-8189 according to randomization

Part 1 (Panels A, B, C) Placebo; Part 2 (Panels D, E, F, G) Placebo

Elpipodect DRUG

MK-8189, oral, 4 mg and/or 12 mg tablets for a total daily dose of 8, 16 or 24 mg QD according to randomization

Also known as: MK-8189

Part 1 (Panel A) Elpipodect; Part 1 (Panel B) Elpipodect; Part 1 (Panel C) Elpipodect; Part 2 (Panel D) Elpipodect; Part 2 (Panel E) Elpipodect; Part 2 (Panel F) Elpipodect; Part 2 (Panel G) Elpipodect

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a body mass index (BMI) ≤40 kg/m2
• Has no clinically significant abnormality on 12-lead safety electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to randomization
• Has a normal resting blood pressure (BP: systolic BP is ≥90 millimeter of mercury \[mmHg\] and ≤140 mmHg; diastolic BP is ≥60 mmHg and ≤90 mmHg) and normal resting heart rate (≥45 beats per minute \[bpm\] and ≤100 bpm) in the semirecumbent position at the prestudy (screening) visit and/or prior to randomization. Repeat evaluations may be done if the values for a participant are, per investigator discretion, minimally outside the designated range. Participants may be included if values are outside the normal range but considered not clinically significant per investigator discretion
• Participants with schizophrenia only: Meets diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (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
• Participants with schizophrenia only: Has a total Brief Psychiatric Rating Scale (BPRS) score of \<48 with a BPRS score \<4 for #10 (hostility) and #14 (uncooperativeness) at the screening visit
• Participants with schizophrenia only: Is in the nonacute phase of their illness and clinically stable for 3 months prior to screening as demonstrated by the following: 1) 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 2) no increase in level of psychiatric care due to worsening of symptoms of schizophrenia for 3 months prior to screening
• Participants with schizophrenia only: Has a history of receiving and tolerating antipsychotic medication within the usual dose range employed for schizophrenia
• Participants with schizophrenia only: Has a stable living situation
• Participants with hypothyroidism, diabetes, high BP, chronic respiratory conditions or other mild forms of these medical conditions could be considered as candidates for study enrollment if their condition is stable
• Has regular bowel movements
• Participants with schizophrenia only: 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
• Female participants are not pregnant and not breastfeeding, and are not a woman of childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 14 days after the last dose of study intervention

You may not qualify if:

• Is a WOCBP who has a positive urine pregnancy test within 48 hours before the first dose of study intervention
• Participants with schizophrenia only: 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 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
• Has a substance-induced psychotic disorder or behavioral disturbance thought to be due to substance abuse
• Has a DSM-5 defined substance use disorder within 3 months of screening
• Has a history of seizure disorder beyond childhood or is receiving treatment with any anticonvulsant to prevent seizures
• Has an untreated or uncompensated clinically significant renal, endocrine, hepatic, respiratory, gastrointestinal, psychiatric, neurologic, cardiovascular, hematological, immunological or cerebrovascular disease, malignancy, allergic disease or other chronic and/or degenerative process at screening
• Has any clinically significant abnormal laboratory, vital sign (VS), physical examination, or 12-lead safety ECG findings at screening or changes from baseline parameters or, in the opinion of the investigator, would make the participant inappropriate for entry into this study
• Has a history of cancer with following exceptions: 1) Adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or; 2) Other malignancies which have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study, in the opinion of the investigator and with agreement of the Sponsor
• Has a clinically significant history or presence of sick sinus syndrome, first, second, or third-degree AV block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged corrected QT (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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (6)

Woodland Research Northwest, LLC ( Site 0002)

Rogers, Arkansas, 72758-6442, United States

Location

Parexel ( Site 0004)

Glendale, California, 91206, United States

Location

Collaborative NeuroScience Network ( Site 0008)

Long Beach, California, 90806, United States

Location

Velocity Clinical Research, Hallandale Beach ( Site 0001)

Hallandale, Florida, 33009, United States

Location

RCA at Fort Lauderdale Behavioral Health Center ( Site 0006)

Oakland Park, Florida, 33334, United States

Location

Hassman Research Institute ( Site 0007)

Berlin, New Jersey, 08009, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Schizophrenia

Interventions

MK-8189

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2020
• First Posted: August 10, 2020
• Study Start: August 28, 2020
• Primary Completion: March 22, 2022
• Study Completion: March 22, 2022
• Last Updated: April 29, 2026
• Results First Posted: October 2, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (6)