Elpipodect (MK-8189) Multiple Dose Study in Healthy Volunteers and Schizophrenia Participants (MK-8189-003)

NCT02181803 | Completed Phase 1 Results

• 1 other identifier: 8189-003
• Study Type: interventional
• Target: 55
• Locations: 0 countries
• Sites: N/A

Brief Summary

This 3-part dose titration study will assess elpipodect safety, tolerability, pharmacokinetics (PK), and central nervous system activity. Part 1 (Panels A and B) will assess elpipodect administered as monotherapy in participants with schizophrenia. Part 2 (Panel C) will assess elpipodect administered as add-on to atypical antipsychotic treatment in participants with schizophrenia. Part 3 (Panel D) will assess monotherapy with elpipodect in healthy participants, including those of Japanese descent. The primary hypothesis is that there is at least one dose of elpipodect that is generally safe and well-tolerated which will have the desired PK parameters in participants with schizophrenia.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (7)

• Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 in Schizophrenia Participants

  C24hr was defined as the concentration of MK-8189 observed in plasma at the 24-hour nominal sampling time after administration of MK-8189. In participants receiving MK-8189, blood samples were collected pre-dose and 24 hours post-dose to estimate C24hr following MK-8189 administration. As specified by the protocol, C24hr was analyzed by part, dose and dosing schedule. Due to differing dosing schedules, some time points were not applicable for certain arms/doses as indicated by zero participants analyzed entered in the table. Per protocol, healthy participants (Part 3) and participants receiving placebo were excluded from C24 analysis.

  Day 1, 4, 8, 11 and 14 pre-dose and 24 hours post-dose

• Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC[0-24hr]) of MK-8189 in Schizophrenia Participants

  AUC was defined as a measure of MK-8189 exposure that was calculated as the product of plasma drug concentration and time. The linear-up-log down rule was used to estimate AUC. Blood samples were collected pre-dose and up to 24 hours post-dose to estimate AUC(0-24hr) following MK-8189 administration. As specified by the protocol, AUC(0-24hr) was analyzed by part, dose and dosing schedule. Due to differing dosing schedules, some time points were not applicable for certain arms/doses as indicated by zero participants analyzed entered in the table. Per protocol, healthy participants (Part 3) and participants receiving placebo were excluded from AUC(0-24hr) analysis.

  Day 1 pre-dose and 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post-dose; Days 4, 8, 11 pre-dose and 6, 10, 16, 24 hours post-dose; Day 14 pre-dose and 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hours post-dose

• Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 in Schizophrenia Participants

  Cmax was defined as the maximum concentration of MK-8189 observed in plasma. Blood samples were collected pre-dose and up to 48 hours post-dose at multiple time points to estimate Cmax following MK-8189 administration. As specified by the protocol, Cmax was analyzed by part, dose and dosing schedule. Due to differing dosing schedules, some time points were not applicable for certain arms/doses as indicated by zero participants analyzed entered in the table. Per protocol, healthy participants (Part 3) and participants receiving placebo were excluded from Cmax analysis.

  Day 1 pre-dose and 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post-dose; Days 4, 8, 11 pre-dose and 6, 10, 16, 24 hours post-dose; Day 14 pre-dose and 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 36, 48 hours post-dose

• Time Post-dose at Which the Maximum Plasma Concentration (Tmax) of MK-8189 Was Observed in Schizophrenia Participants

  Tmax was defined as the time required post dose to reach a maximum plasma concentration of MK-8189. It was estimated as the actual sampling time at the highest MK-8189 plasma concentration. Blood samples were collected pre-dose and up to 48 hours post-dose at multiple time points to estimate Tmax following MK-8189 administration. As specified by the protocol, Tmax was analyzed by part, dose and dosing schedule. Due to differing dosing schedules, some time points were not applicable for certain arms/doses as indicated by zero participants analyzed entered in the table. Per protocol, healthy participants (Part 3) and participants receiving placebo were excluded from Tmax analysis.

  Day 1 pre-dose and 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post-dose; Days 4, 8, 11 pre-dose and 6, 10, 16, 24 hours post-dose; Day 14 pre-dose and 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 36, 48 hours post-dose

• Time Required for Plasma Concentration of MK-8189 to Decrease by Half (Apparent t1/2) in Schizophrenia Participants on Day 14

  t1/2 was defined as the time required to divide the MK-8189 plasma concentration by half after reaching pseudo-equilibrium. At least three quantifiable post-Cmax, terminal phase concentrations collected were used to calculate the apparent t1/2. Blood samples were collected pre-dose and up to 48 hours post-dose at multiple time points on Day 14 to estimate t1/2 following MK-8189 administration. As specified by the protocol, t1/2 was analyzed by part, dose and dosing schedule. Due to differing dosing schedules, the Day 14 timepoint was not applicable for certain arms/doses as indicated by zero participants analyzed entered in the table. Per protocol, healthy participants (Part 3) and participants receiving placebo were excluded from t1/2 analysis.

  Day 14 pre-dose and 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 36, 48 hours post-dose

• Number of Participants Experiencing an Adverse Event (AE)

  An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced at least one AE were reported.

  Up to Day 28

• Number of Participants Who Discontinue From Study Treatment Due to an AE

  An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE were reported.

  Up to Day 14

Secondary Outcomes (2)

• Change From Baseline at Day 13 in Mismatched Negativity (MMN) Peak Amplitude in Monotherapy MK-8189-treated Schizophrenia Participants

  Baseline and Day 13

• Change From Baseline at Day 13 in Mismatched Negativity (MMN) Area Under Curve (AUC) in Monotherapy MK-8189-treated Schizophrenia Participants

  Baseline and Day 13

Study Arms (7)

Part 1 Panel A & B Elpipodect Monotherapy 2-40 mg: Schizophrenic

EXPERIMENTAL

Participants with schizophrenia will receive monotherapy of elpipodect in escalating doses starting at 2 mg once daily (QD) up to 40 mg QD, depending on safety and tolerability

Drug: Elpipodect

Part 2 Panel C Elpipodect Add-on Therapy 2-20 mg: Schizophrenic

EXPERIMENTAL

Participants with schizophrenia will receive add-on therapy of elpipodect in escalating doses starting at 2 mg QD up to 20 mg QD, depending on safety and tolerability

Drug: Elpipodect; Drug: Base Monotherapy

Part 2 Panel C Elpipodect Add-on Therapy 4-20 mg: Schizophrenic

EXPERIMENTAL

Participants with schizophrenia will receive add-on therapy of elpipodect in escalating doses starting at 4 mg QD up to 20 mg QD, depending on safety and tolerability

Drug: Elpipodect; Drug: Base Monotherapy

Part 3 Panel D Elpipodect Monotherapy 2-16 mg: Healthy

EXPERIMENTAL

Healthy participants will receive monotherapy of elpipodect in escalating doses starting at 2 mg QD up to 16 mg QD, depending on safety and tolerability

Drug: Elpipodect

Part 1 Panel A & B Placebo Monotherapy: Schizophrenic

PLACEBO COMPARATOR

Participants with schizophrenia will receive dose-matched placebo to elpipodect monotherapy

Drug: Placebo

Part 2 Panel C Placebo Add-on Therapy: Schizophrenic

PLACEBO COMPARATOR

Participants with schizophrenia will receive dose-matched placebo to elpipodect add-on therapy

Drug: Placebo; Drug: Base Monotherapy

Part 3 Panel D Placebo Monotherapy: Healthy

PLACEBO COMPARATOR

Healthy participants will receive dose-matched placebo to elpipodect monotherapy

Drug: Placebo

Interventions

Placebo DRUG

Placebo matching oral 2 mg and/or 10 mg MK-8189 tablets, taken QD

Part 1 Panel A & B Placebo Monotherapy: Schizophrenic; Part 2 Panel C Placebo Add-on Therapy: Schizophrenic; Part 3 Panel D Placebo Monotherapy: Healthy

Base Monotherapy DRUG

For Part 2 only: participants need to be on monotherapy with an atypical antipsychotic medication (eg, Olanzapine, Quetiapine, Paliperidone, Asenapine, Iloperidone, Aripirprazole, Lurasidone, Risperidone \[not to exceed daily dose of 6 mg\], or Ziprasidone.) The participant should be on a stable and well tolerated treatment regimen for at least 2 months prior to screening. NOTE: Clozapine is not allowed.

Part 2 Panel C Elpipodect Add-on Therapy 2-20 mg: Schizophrenic; Part 2 Panel C Elpipodect Add-on Therapy 4-20 mg: Schizophrenic; Part 2 Panel C Placebo Add-on Therapy: Schizophrenic

Elpipodect DRUG

MK-8189, oral, 2 mg and/or 10 mg tablets, taken QD for a total daily dose of 2 mg, 4 mg, 8 mg, 10 mg, 12 mg, 14 mg, 16 mg, 20 mg, or 40 mg

Also known as: MK-8189

Part 1 Panel A & B Elpipodect Monotherapy 2-40 mg: Schizophrenic; Part 2 Panel C Elpipodect Add-on Therapy 2-20 mg: Schizophrenic; Part 2 Panel C Elpipodect Add-on Therapy 4-20 mg: Schizophrenic; Part 3 Panel D Elpipodect Monotherapy 2-16 mg: Healthy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or non-pregnant and non-breast feeding female. If participant is male with a female partner of child-bearing potential, participant must agree to use a medically acceptable method of contraception during the trial and for 120 days after the last dose of trial drug. If their partner is pregnant, males must agree to use a condom
• Body Mass Index (BMI) ≥ 18.5 and ≤ 40 kg/m\^2
• Meet diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria with the onset of the first episode being no less than 2 years prior to study entry
• Be in the non-acute phase of illness and clinically stable for 3 months prior to screening
• History of receiving and tolerating antipsychotic medication within the usual dose range employed for schizophrenia
• 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 comedication during the study
• Has a negative urinary drug screen at screening
• Male, or non-pregnant and non-breast feeding female of Japanese or non-Japanese descent. If participant is male with a female partner of child-bearing potential, participant must agree to use a medically acceptable method of contraception during the trial and for 120 days after the last dose of trial drug. If their partner is pregnant, males must agree to use a condom
• Body Mass Index (BMI) ≥ 18.5 and ≤ 35 kg/m\^2
• In good health
• Nonsmoker and/or has not used nicotine or nicotine-containing products (e.g., nicotine patch) for at least approximately 3 months
• Has a negative urinary drug screen at screening

You may not qualify if:

• DSM-IV axis I psychiatric diagnosis other than schizophrenia or schizoaffective disorder within one month of screening
• Has evidence or history of mental retardation, borderline personality disorder, anxiety disorder, or organic brain syndrome
• History of neuroleptic malignant syndrome or moderate to severe tardive dyskinesia
• Untreated or uncompensated clinically significant renal, endocrine, hepatic, respiratory, gastrointestinal, psychiatric, neurologic, cardiovascular, hematological, immunological or cerebrovascular disease, malignance, allergic disease or other chronic and/or degenerative process at screening
• Has a history of cancer (malignancy) with certain exceptions
• Treatment with clozapine for schizophrenia or treatment with monoamine oxidase inhibitors within 3 months of screening
• Received a parenteral depot antipsychotic medication within 3 months of screening
• Participated in another investigational study within 4 weeks, prior to screening
• History of clinically significant endocrine, gastrointestinal, cardiovascular (including hypertension, angina, coronary artery disease, valvular disease, heart rate or rhythm abnormalities), hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases
• Mentally or legally incapacitated
• History of clinically diagnosed depression, anxiety disorder, or any history of psychiatric disorders having required drug treatment or hospitalization
• History of cancer (malignancy)
• Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies throughout the trial
• Participated in another investigational study within 4 weeks, prior to screening

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Schizophrenia

Interventions

MK-8189

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Limitations and Caveats

There were some missing event markers in EEG recordings during data collection, these were imputed for the MMN analyses.

Results Point of Contact

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

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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2014
• First Posted: July 4, 2014
• Study Start: August 5, 2014
• Primary Completion: April 23, 2015
• Study Completion: April 23, 2015
• Last Updated: April 29, 2026
• Results First Posted: March 27, 2020

Record last verified: 2026-04