Phase 1
N=107
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)
Schizophrenia
Bottom Line
View on ClinicalTrials.gov: NCT05893862 ↗Enrolled (actual)
107
Serious AEs
0.4%
Results posted
Apr 2025
Primary outcome: Primary: Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following MK-8189 Treatment — 4.31; -1.38; -0.61; -1.13 ΔQTcF (msec)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Elpipodect (Drug); Moxifloxacin (Drug); Placebo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Feb 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following MK-8189 Treatment |
4.31; -1.38; -0.61; -1.13; 0.29; 0.48 | — |
| PRIMARY Number of Participants With Adverse Events (AEs) |
25; 16; 21; 7; 11 | — |
| PRIMARY Number of Participants Discontinuing Study Therapy Due to AE |
3; 1; 4; 0; 2 | — |
| SECONDARY Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following Moxifloxacin Treatment |
-1.38; 0.92; -1.38; -0.76; 9.77; 0.92 | <0.0001 sig |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of MK-8189 |
18500; 41200 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of MK-8189 |
17400; 54100 | — |
| SECONDARY Maximum Concentration (Cmax) of MK-8189 |
1290; 2360 | — |
| SECONDARY Concentration of MK-8189 at 24 Hours (C24) Post-dose |
992; 1660 | — |
| SECONDARY Apparent Terminal Half-life (t½) of MK-8189 |
9.89 | — |
| SECONDARY Time to Maximum Concentration (Tmax) of MK-8189 |
14.08; 14.13 | — |
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).
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT05893862). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.