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) (TQT)

A Double-Blind, Cross-Over Placebo-Controlled and Active-Controlled Trial To Evaluate The Effect Of A Supratherapeutic Dose Of MK-8189 On The QTc Interval In Participants With Schizophrenia

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).

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Moxifloxacin; Drug: Elpipodect

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • California Clinical Trials Medical Group managed by PAREXEL-PAREXEL International ( Site 0003)
    • Orange, California, United States, 92868
      • NRC Research Institute ( Site 0004)
  • Florida
    • Hallandale, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach ( Site 0002)
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute Marlton Site ( Site 0001)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1: Elpipodect (Treatment A)→Moxifloxacin (Treatment B)→Placebo (Treatment C); 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: Placebo; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Elpipodect; Oral Tablet; Other Names: MK-8189
Experimental: Sequence 2: Moxifloxacin (Treatment B) →Placebo (Treatment C) →Elpipodect (Treatment A); 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: Placebo; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Elpipodect; Oral Tablet; Other Names: MK-8189
Experimental: Sequence 3: Placebo (Treatment C) →Elpipodect (Treatment A) →Moxifloxacin (Treatment B); 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: Placebo; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Elpipodect; Oral Tablet; Other Names: MK-8189
Experimental: Sequence 4: Moxifloxacin (Treatment B) →Elpipodect (Treatment A) → Placebo (Treatment C); 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: Placebo; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Elpipodect; Oral Tablet; Other Names: MK-8189
Experimental: Sequence 5: Elpipodect (Treatment A) →Placebo (Treatment C) →Moxifloxacin (Treatment B); 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: Placebo; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Elpipodect; Oral Tablet; Other Names: MK-8189
Experimental: Sequence 6: Placebo (Treatment C) →Moxifloxacin (Treatment B) → Elpipodect (Treatment A); 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: Placebo; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Elpipodect; Oral Tablet; Other Names: MK-8189

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following Moxifloxacin 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 secondary endpoint compares moxifloxacin to placebo on Day 2. Moxifloxacin was tested for statistical significance 1 to 4 hours postdose (ie, around moxifloxacin Cmax) to ensure assay sensitivity. Hochberg's step-up method was applied to preserve the overall α level at .05 for the hypothesis testing.	Day 2
Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of MK-8189	AUC0-24 is defined as the area under concentration-time curve from 0 to 24 hours postdose. Blood samples taken at pre-dose and up to 24 hours post-dose will be used to determine the 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	AUC0-last is defined as the area under concentration-time curve from 0 to 24 hours. Blood samples taken at pre-dose and up to 72 hours post-dose will be used to extrapolate the 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	Cmax is the maximum plasma concentration 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	C24 is the plasma concentration 24 hours postdose.	Day 1 and Day 2: 24 hours postdose
Apparent Terminal Half-life (t½) of MK-8189	t½ is the time required for the Cmax plasma concentration to reduce by 50%. Per protocol, t½ was determined only for MK-8189 80 mg.	Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose
Time to Maximum Concentration (Tmax) of MK-8189	Tmax is defined as the time to reach Cmax.	Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14, and 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, and 72 hours postdose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2023
• Primary Completion (Actual): February 22, 2024
• Study Completion (Actual): February 22, 2024

Study Registration Dates

• First Submitted: May 30, 2023
• First Submitted That Met QC Criteria: May 30, 2023
• First Posted (Actual): June 8, 2023

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Moxifloxacin; MK-8189
• Other Study ID Numbers: 8189-019; MK-8189-019 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No