NCT05893862: 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)

Completed Phase 1 Results posted Last updated 22 April 2025

What this trial tests

Phase 1 trial testing MK-8189 in Schizophrenia in 107 participants. Completed in 22 February 2024.

Timeline

26 June 2023

Primary endpoint
22 February 2024

22 February 2024

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	107
Start date	26 June 2023
Primary completion	22 February 2024
Estimated completion	22 February 2024
Sites	4 locations across United States

Drugs / interventions tested

• MK-8189 — full drug profile →
• Moxifloxacin (moxifloxacin) — full drug profile →
• Placebo

Conditions studied

• Schizophrenia — all drugs for Schizophrenia →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 60, any sex, with Schizophrenia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following Moxifloxacin Treatment Secondary · 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, a

Predose (Day 2 only)

Group	Value	95% CI
Placebo Day 2	-1.38	-3.24 – 0.49
Moxifloxacin 400 mg Day 2	0.92	-0.80 – 2.65

0.5 hr (Day 1 only)

Group	Value	95% CI
Placebo Day 2	-1.38	-3.24 – 0.49

1 hr

Group	Value	95% CI
Placebo Day 2	-0.76	-2.95 – 1.43
Moxifloxacin 400 mg Day 2	9.77	7.34 – 12.20

2 hr

Group	Value	95% CI
Placebo Day 2	0.92	-1.74 – 3.58
Moxifloxacin 400 mg Day 2	11.03	8.53 – 13.53

3 hr

Group	Value	95% CI
Placebo Day 2	-2.22	-5.17 – 0.72
Moxifloxacin 400 mg Day 2	8.92	6.28 – 11.57

4 hr

Group	Value	95% CI
Placebo Day 2	-2.67	-5.40 – 0.05
Moxifloxacin 400 mg Day 2	4.70	1.84 – 7.57

8 hr

Group	Value	95% CI
Placebo Day 2	-3.10	-5.82 – -0.39
Moxifloxacin 400 mg Day 2	3.50	1.05 – 5.95

11 hr

Group	Value	95% CI
Placebo Day 2	-1.93	-4.83 – 0.98
Moxifloxacin 400 mg Day 2	5.45	2.85 – 8.04

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

Group	Value	95% CI
MK-8189 48 mg Day 1	18500	± 50.2
MK-8189 80 mg Day 2	41200	± 54.0

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

Group	Value	95% CI
MK-8189 48 mg Day 1	17400	± 61.6
MK-8189 80 mg Day 2	54100	± 95.9

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

Predose (Day 2 only)

Group	Value	95% CI
MK-8189 80 mg Day 2	4.31	2.45 – 6.16
Placebo Day 2	-1.38	-3.24 – 0.49

0.5 Hr

Group	Value	95% CI
MK-8189 48 mg Day 1	-0.61	-1.87 – 0.66
Placebo Day 1	-1.13	-2.84 – 0.57

1 hr

Group	Value	95% CI
MK-8189 48 mg Day 1	0.29	-1.50 – 2.08
Placebo Day 1	0.48	-1.25 – 2.20
MK-8189 80 mg Day 2	3.60	1.33 – 5.87
Placebo Day 2	-0.76	-2.95 – 1.43

2 hr

Group	Value	95% CI
MK-8189 48 mg Day 1	2.68	0.21 – 5.16
Placebo Day 1	1.06	-1.35 – 3.46
MK-8189 80 mg Day 2	5.14	2.40 – 7.87
Placebo Day 2	0.92	-1.74 – 3.58

3 hr

Group	Value	95% CI
MK-8189 48 mg Day 1	2.18	-0.61 – 4.97
Placebo Day 1	-1.35	-4.03 – 1.34
MK-8189 80 mg Day 2	3.31	0.50 – 6.11
Placebo Day 2	-2.22	-5.17 – 0.72

4 hr

Group	Value	95% CI
MK-8189 48 mg Day 1	2.80	0.07 – 5.53
Placebo Day 1	-3.19	-5.73 – -0.64
MK-8189 80 mg Day 2	2.64	0.11 – 5.16
Placebo Day 2	-2.67	-5.40 – 0.05

6 hr (Day 1 only)

Group	Value	95% CI
MK-8189 48 mg Day 1	7.38	4.75 – 10.00
Placebo Day 1	0.25	-2.51 – 3.02
Placebo Day 2	-3.10	-5.82 – -0.39

8 hr

Group	Value	95% CI
MK-8189 48 mg Day 1	8.75	6.51 – 10.98
Placebo Day 1	-0.97	-3.57 – 1.64
MK-8189 80 mg Day 2	2.82	0.25 – 5.40
Placebo Day 2	-1.93	-4.83 – 0.98

Number of Participants With Adverse Events (AEs) Primary · 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.

Group	Value	95% CI
MK-8189 48 mg Day 1	25
Placebo Days 1 and 2	16
MK-8189 80 mg Day 2	21
Standard Image Placebo Day 1	7
Moxifloxacin 400 mg Day 2	11

Maximum Concentration (Cmax) of MK-8189 Secondary · 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.

Group	Value	95% CI
MK-8189 48 mg Day 1	1290	± 50.6
MK-8189 80 mg Day 2	2360	± 52.4

Concentration of MK-8189 at 24 Hours (C24) Post-dose Secondary · Day 1 and Day 2: 24 hours postdose

C24 is the plasma concentration 24 hours postdose.

Group	Value	95% CI
MK-8189 48 mg Day 1	992	± 83.7
MK-8189 80 mg Day 2	1660	± 87.4

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

Group	Value	95% CI
MK-8189 80 mg	9.89	± 29.2

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

Group	Value	95% CI
MK-8189 48 mg	14.08	6.13 – 25.42
MK-8189 80 mg	14.13	0.00 – 35.95

Number of Participants Discontinuing Study Therapy Due to AE Primary · 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.

Group	Value	95% CI
MK-8189 48 mg Day 1	3
Placebo Days 1 and 2	1
MK-8189 80 mg Day 2	4
Standard Image Placebo Day 1	0
Moxifloxacin 400 mg Day 2	2

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to ~30 days after each dose. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MK-8189 48 mg

Serious: 1/98 (1%)

Deaths: 0/98

MK-8189 80 mg

Serious: 0/92 (0%)

Deaths: 0/92

MK-8189 Placebo

Serious: 1/90 (1%)

Deaths: 0/90

Standard Image Placebo Day 1

Serious: 0/89 (0%)

Deaths: 0/89

Moxifloxacin 400 mg Day 2

Serious: 0/89 (0%)

Deaths: 0/89

Serious adverse events (2 terms)

Reaction	System	MK-8189 48 mg	MK-8189 80 mg	MK-8189 Placebo	Standard Image Placebo Day 1	Moxifloxacin 400 mg Day 2
Anaphylactic reaction	Immune system disorders	—	—	—	—	—
Schizophrenia	Psychiatric disorders	—	—	—	—	—

Other adverse events (63 terms — click to expand)

Reaction	System	MK-8189 48 mg	MK-8189 80 mg	MK-8189 Placebo	Standard Image Placebo Day 1	Moxifloxacin 400 mg Day 2
Dystonia	Nervous system disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Akathisia	Nervous system disorders	—	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Oromandibular dystonia	Nervous system disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—
Feeling of body temperature change	General disorders	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Tremor	Nervous system disorders	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—
Hyperhidrosis	Skin and subcutaneous tissue disorders	—	—	—	—	—
Psychotic disorder	Psychiatric disorders	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—
Sinus tachycardia	Cardiac disorders	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—
Tinnitus	Ear and labyrinth disorders	—	—	—	—	—
Excessive eye blinking	Eye disorders	—	—	—	—	—
Lip swelling	Gastrointestinal disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Application site injury	General disorders	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Medical device site irritation	General disorders	—	—	—	—	—
Withdrawal Syndrome	General disorders	—	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—
Blood glucose increased	Investigations	—	—	—	—	—
Blood pressure increased	Investigations	—	—	—	—	—
Heart rate increased	Investigations	—	—	—	—	—
Orthostatic heart rate response increased	Investigations	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—
Joint contracture	Musculoskeletal and connective tissue disorders	—	—	—	—	—

Most-reported serious reactions: Anaphylactic reaction, Schizophrenia.

Data from ClinicalTrials.gov NCT05893862 adverse events section.

Sponsor's own description

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 effects of 3 treatment sequences 1) MK-8189 (48 mg \[Day 1\] and 80 mg \[Day2\]); 2) standard image placebo (Day 1) and moxifloxacin 400 mg (Day 2); and 3) MK-8189 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 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).

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Unlocking the potential of lumateperone and novel anti-psychotics for schizophrenia.
   Ahmad SR, Zeyaullah M, AlShahrani AM, Khan MS, et al · · 2025 · PMID 40161932 · DOI 10.34172/bi.30259