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Completed

NCT Number: NCT05893862

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)

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).

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Key information

Conditions

Schizophrenia Mental Disorders Schizophrenia Spectrum and Other Psychotic Disorders

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

California Clinical Trials Medical Group managed by PAREXEL-PAREXEL International ( Site 0003), Glendale, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Elpipodect

Drug

Oral Tablet

Other names: MK-8189

moxifloxacin

Drug

Oral Tablet

Placebo

Drug

Oral Tablet

Primary outcomes

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

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

    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.

  2. Number of Participants With Adverse Events (AEs)

    Time frame: Up to ~30 days after each dose

    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.

  3. Number of Participants Discontinuing Study Therapy Due to AE

    Time frame: Up to ~30 days after each dose

    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.

Secondary outcomes

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

    Time frame: Day 2

    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.

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

    Time frame: 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

    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.

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

    Time frame: 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

    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.

  4. Maximum Concentration (Cmax) of MK-8189

    Time frame: 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

    Cmax is the maximum plasma concentration of MK-8189.

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

    Time frame: Day 1 and Day 2: 24 hours postdose

    C24 is the plasma concentration 24 hours postdose.

  6. Apparent Terminal Half-life (t½) of MK-8189

    Time frame: Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose

    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.

  7. Time to Maximum Concentration (Tmax) of MK-8189

    Time frame: 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

    Tmax is defined as the time to reach Cmax.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

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

Acronym: TQT

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Jun 8, 2023
Registry last updated
Apr 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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