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

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05893862
• Collaborator: (none)
• Enrollment: 84
• Arms: 6
• Anticipated Duration (Months): 7

Study Details

Study Description

Brief Summary

The primary purpose of this study to evaluate the effect of a supratherapeutic dose of 80 mg MK-8189 on the QT interval corrected for heart rate (QTc interval) and to assess the safety and tolerability of multiple once-daily doses of MK-8189 in participants with schizophrenia.

The primary hypothesis is that the administration of an 80 mg MK-8189 dose on Day 2 does not prolong the QTc interval to a clinically significant degree. Specifically, the true mean difference (MK-8189 - placebo) in QTc change from baseline is less than 10 milliseconds (msec).

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: MK-8189; Drug: Moxifloxacin; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official 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
• Anticipated Study Start Date: Jun 26, 2023
• Anticipated Primary Completion Date: Jan 24, 2024
• Anticipated Study Completion Date: Jan 24, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequence 1: MK-8189 (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 MK-8189 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: MK-8189; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Placebo; Oral Tablet
Experimental: Sequence 2: Moxifloxacin (Treatment B) →Placebo (Treatment C) →MK-8189 (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 MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2.	Drug: MK-8189; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Placebo; Oral Tablet
Experimental: Sequence 3: Placebo (Treatment C) →MK-8189 (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 MK-8189 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: MK-8189; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Placebo; Oral Tablet
Experimental: Sequence 4: Moxifloxacin (Treatment B) → MK-8189 (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 MK-8189 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: MK-8189; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Placebo; Oral Tablet
Experimental: Sequence 5: MK-8189 (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 MK-8189 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: MK-8189; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Placebo; Oral Tablet
Experimental: Sequence 6: Placebo (Treatment C) →Moxifloxacin (Treatment B) → MK-8189 (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 MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2.	Drug: MK-8189; Oral Tablet; Drug: Moxifloxacin; Oral Tablet; Drug: Placebo; Oral Tablet

Outcome Measures

Primary Outcome Measures

1. Change from baseline in QT interval corrected for heart rate (QTc) following MK-8189 treatment [Baseline and up to 3 days]

   Electrocardiogram data will be obtained using a digital Holter device and the Fridericia correction of the QT interval (QTcF) will be determined. The change from baseline in QTcF will be calculated by subtracting the QTcF value at the timepoint from the QTcF baseline value.

2. Number of participants with adverse events (AEs) [Up to ~30 days]

   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 who discontinue study drug due to an AE [Up to ~16 days]

   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 Outcome Measures

1. Change from baseline in QT interval corrected for heart rate (QTc) following moxifloxacin treatment [Baseline and up to 3 days]

   Electrocardiogram data will be obtained using a digital Holter device and the Fridericia correction of the QT interval (QTcF) will be determined. The change from baseline in QTcF wil be calculated by subtracting the QTcF value at the timepoint from the QTcF baseline value.

2. Area Under the Plasma Concentration-Time curve From Time 0 to 24 hours (AUC0-24) of MK-8189 [Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14 hours postdose; Day 2: Predose, 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. 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 quantifiable concentration (AUC0-last) of MK-8189 [Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14 hours postdose; Day 2: Predose, 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose]

   AUC0-last is the area under the plasma concentration-time curve from time zero to time of last measurable concentration. Blood samples taken at pre-dose and at multiple timepoints post-dose will be used to determine the AUC0-last of MK-8189.

4. Maximum Concentration (Cmax) of MK-8189 [Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14 hours postdose; Day 2: Predose, 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose]

   Cmax is defined as the maximum concentration of MK-8189 observed in plasma. Blood samples taken at pre-dose and at multiple timepoints post-dose will be used to determine the Cmax of MK-8189.

5. Concentration of MK-8189 at 24 Hours (C24) post-dose [24 hours post-dose]

   C24 is defined as the concentration of MK-8189 observed in plasma at 24 hours. Blood samples taken at 24 hours post-dose will be used to determine the C24 of MK-8189.

6. Time to maximum concentration (Tmax) of MK-8189 [Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14 hours postdose; Day 2: Predose, 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose]

   Tmax is defined as the time to maximum concentration of MK-8189 observed in plasma. Blood samples taken at pre-dose and at multiple timepoints post-dose will be used to determine the Tmax of MK-8189.

7. Apparent Terminal Half-life (t1/2) of MK-8189 [Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14 hours postdose; Day 2: Predose, 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose]

   t1/2 is defined as the time required to divide the plasma concentration of MK-8189 by half after reaching pseudo-equilibrium. Blood samples taken at pre-dose and at multiple timepoints post-dose will be used to determine the t1/2 of MK-8189.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT05893862
• Other Study ID Numbers: 8189-019; MK-8189-019
• First Posted: Jun 8, 2023
• Last Update Posted: Jun 8, 2023
• Last Verified: May 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Schizophrenia; Moxifloxacin

Study Results

No Results Posted as of Jun 8, 2023