A Study To Evaluate The Effect Of A Supratherapeutic Dose Of Elpipodect (MK-8189) On The QTc Interval In Participants With Schizophrenia (MK-8189-019)

NCT05893862 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 8189-019MK-8189-019
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 4

Brief Summary

The primary purpose of this study to evaluate the effect of a supratherapeutic dose of 80 mg elpipodect on the QT interval corrected for heart rate (QTc interval) and to assess the safety and tolerability of multiple once-daily doses of elpipodect in participants with schizophrenia. The effects of 3 treatment sequences 1) elpipodect (48 mg \[Day 1\] and 80 mg \[Day2\]); 2) standard image placebo (Day 1) and moxifloxacin 400 mg (Day 2); and 3) elpipodect placebo (Day 1 and Day 2) were assessed with 5-day washout intervening sequence. Participants received all treatments in a counter-balanced order according to 1 of 6 possible treatment sequences. The primary hypothesis is that the administration of an 80 mg elpipodect dose on Day 2 does not prolong the QTc interval to a clinically significant degree. Specifically, the true mean difference (elpipodect - placebo) in QTc change from baseline is less than 10 milliseconds (msec).

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following MK-8189 Treatment

  Electrocardiogram data was obtained using a digital Holter device and the Fridericia correction of the QT interval (QTcF) was determined. The change from baseline in QTcF (ΔQTcF \[msec\]) was calculated by subtracting the QTcF value at the timepoint from the QTcF baseline value. Negative values represent a decrease from baseline and vice versa. An average of up to 9 predose ECGs on Day 1 served as baseline to compare postdose effects. Per protocol, the primary endpoint compares MK-8189 to placebo.

  Day 1 (MK-8189 48 mg and placebo) and Day 2 (MK-8189 80 mg and placebo)

• Number of Participants With Adverse Events (AEs)

  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 ~30 days after each dose

• Number of Participants Discontinuing Study Therapy Due to AE

  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 ~30 days after each dose

Secondary Outcomes (7)

• Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following Moxifloxacin Treatment

  Day 2

• Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of MK-8189

  Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24 hours postdose

• Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of MK-8189

  Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, and 72 hours postdose

• Maximum Concentration (Cmax) of MK-8189

  Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose

• Concentration of MK-8189 at 24 Hours (C24) Post-dose

  Day 1 and Day 2: 24 hours postdose

Study Arms (6)

Sequence 1: Elpipodect (Treatment A)→Moxifloxacin (Treatment B)→Placebo (Treatment C)

EXPERIMENTAL

Participants receive a sequence of Treatment A in Period 1 followed by Treatment B in Period 2 followed by Treatment C in Period 3; there will be a 5-day washout between periods. Treatment A consists of elpipodect administered orally at 48 mg on Day 1 and 80 mg on day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2.

Drug: Elpipodect; Drug: Moxifloxacin; Drug: Placebo

Sequence 2: Moxifloxacin (Treatment B) →Placebo (Treatment C) →Elpipodect (Treatment A)

EXPERIMENTAL

Participants receive a sequence of Treatment B in Period 1 followed by Treatment C in Period 2 followed by Treatment A in Period 3; there will be a 5-day washout between periods. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment A consists of elpipodect administered orally at 48 mg on Day 1 and 80 mg on Day 2.

Drug: Elpipodect; Drug: Moxifloxacin; Drug: Placebo

Sequence 3: Placebo (Treatment C) →Elpipodect (Treatment A) →Moxifloxacin (Treatment B)

EXPERIMENTAL

Participants receive a sequence of Treatment C in Period 1 followed by Treatment A in in Period 2 followed by Treatment B in Period 3; there will be a 5-day washout between periods. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment A consists of elpipodect administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2.

Drug: Elpipodect; Drug: Moxifloxacin; Drug: Placebo

Sequence 4: Moxifloxacin (Treatment B) →Elpipodect (Treatment A) → Placebo (Treatment C)

EXPERIMENTAL

Participants receive a sequence of Treatment B in Period 1 followed by Treatment A in Period 2 followed by Treatment C in Period 3; there will be a 5-day washout between periods. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment A consists of elpipodect administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2.

Drug: Elpipodect; Drug: Moxifloxacin; Drug: Placebo

Sequence 5: Elpipodect (Treatment A) →Placebo (Treatment C) →Moxifloxacin (Treatment B)

EXPERIMENTAL

Participants receive a sequence of Treatment A in Period 1 followed by Treatment C in Period 2 followed by Treatment B in Period 3; there will be a 5-day washout between periods. Treatment A consists of elpipodect administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2.

Drug: Elpipodect; Drug: Moxifloxacin; Drug: Placebo

Sequence 6: Placebo (Treatment C) →Moxifloxacin (Treatment B) → Elpipodect (Treatment A)

EXPERIMENTAL

Participants receive a sequence of Treatment C in Period 1 followed by Treatment B in Period 2 followed by Treatment A in Period 3; there will be a 5-day washout between periods. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment A consists of elpipodect administered orally at 48 mg on Day 1 and 80 mg on Day 2.

Drug: Elpipodect; Drug: Moxifloxacin; Drug: Placebo

Interventions

Moxifloxacin DRUG

Oral Tablet

Sequence 1: Elpipodect (Treatment A)→Moxifloxacin (Treatment B)→Placebo (Treatment C); Sequence 2: Moxifloxacin (Treatment B) →Placebo (Treatment C) →Elpipodect (Treatment A); Sequence 3: Placebo (Treatment C) →Elpipodect (Treatment A) →Moxifloxacin (Treatment B); Sequence 4: Moxifloxacin (Treatment B) →Elpipodect (Treatment A) → Placebo (Treatment C); Sequence 5: Elpipodect (Treatment A) →Placebo (Treatment C) →Moxifloxacin (Treatment B); Sequence 6: Placebo (Treatment C) →Moxifloxacin (Treatment B) → Elpipodect (Treatment A)

Placebo DRUG

Oral Tablet

Sequence 1: Elpipodect (Treatment A)→Moxifloxacin (Treatment B)→Placebo (Treatment C); Sequence 2: Moxifloxacin (Treatment B) →Placebo (Treatment C) →Elpipodect (Treatment A); Sequence 3: Placebo (Treatment C) →Elpipodect (Treatment A) →Moxifloxacin (Treatment B); Sequence 4: Moxifloxacin (Treatment B) →Elpipodect (Treatment A) → Placebo (Treatment C); Sequence 5: Elpipodect (Treatment A) →Placebo (Treatment C) →Moxifloxacin (Treatment B); Sequence 6: Placebo (Treatment C) →Moxifloxacin (Treatment B) → Elpipodect (Treatment A)

Elpipodect DRUG

Oral Tablet

Also known as: MK-8189

Sequence 1: Elpipodect (Treatment A)→Moxifloxacin (Treatment B)→Placebo (Treatment C); Sequence 2: Moxifloxacin (Treatment B) →Placebo (Treatment C) →Elpipodect (Treatment A); Sequence 3: Placebo (Treatment C) →Elpipodect (Treatment A) →Moxifloxacin (Treatment B); Sequence 4: Moxifloxacin (Treatment B) →Elpipodect (Treatment A) → Placebo (Treatment C); Sequence 5: Elpipodect (Treatment A) →Placebo (Treatment C) →Moxifloxacin (Treatment B); Sequence 6: Placebo (Treatment C) →Moxifloxacin (Treatment B) → Elpipodect (Treatment A)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Meets diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria.
• Is in the non-acute phase of their illness.
• Has a history of receiving and tolerating antipsychotics medication within the usual dose range employed for schizophrenia.
• Participants with hypothyroidism, diabetes, high blood pressure, chronic respiratory conditions or other medical conditions could be considered if their condition is stable.

You may not qualify if:

• History of a primary DSM-5 axis I psychiatric diagnosis other than schizophrenia or schizoaffective disorder per the allowed DSM-5 criteria.
• History of intellectual disability, borderline personality disorder, anxiety disorder, or organic brain syndrome.
• History of neuroleptic malignant syndrome or moderate to severe tardive dyskinesia (TD).
• History of seizure disorder beyond childhood or is receiving treatment with any anticonvulsant to prevent seizures.
• History of cancer.
• History or presence of sick sinus syndrome, atrioventricular (AV) block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged QTc interval, or conduction abnormalities.
• History of risk factors for Torsades de Pointes (e.g., heart failure/cardiomyopathy or family history of long QT syndrome).
• History of frequent syncope, vasovagal episodes, or epileptic seizures.
• Family history of sudden cardiac death.
• Has a positive test(s) for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV).
• Had major surgery, donated, or lost 1 unit of blood within 4 weeks prior to the pre-study visit.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (4)

California Clinical Trials Medical Group managed by PAREXEL-PAREXEL International ( Site 0003)

Glendale, California, 91206, United States

Location

NRC Research Institute ( Site 0004)

Orange, California, 92868, United States

Location

Velocity Clinical Research, Hallandale Beach ( Site 0002)

Hallandale, Florida, 33009, United States

Location

Hassman Research Institute Marlton Site ( Site 0001)

Marlton, New Jersey, 08053, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Schizophrenia

Interventions

MK-8189; Moxifloxacin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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

Study Record Dates

• First Submitted: May 30, 2023
• First Posted: June 8, 2023
• Study Start: June 26, 2023
• Primary Completion: February 22, 2024
• Study Completion: February 22, 2024
• Last Updated: April 29, 2026
• Results First Posted: April 22, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (4)