Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT04624243 | Efficacy and Safety of Elpipodect (MK-8189) in Participants With an Acute Episode of Schizophrenia (MK-8189-008) | PHASE2 | COMPLETED | 499 | — | — | Dec 15, 2020 | Jun 21, 2024 | Apr 29, 2026 | 121 | United States, Bulgaria +10 |
| 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) | PHASE1 | COMPLETED | 107 | — | — | Jun 26, 2023 | Feb 22, 2024 | Apr 29, 2026 | 4 | United States |
| NCT05406440 | A Study of Elpipodect (MK-8189) in Participants With Schizophrenia (MK-8189-014) | PHASE1 | COMPLETED | 53 | — | — | Jul 12, 2022 | Feb 24, 2023 | Apr 29, 2026 | 3 | United States |
| NCT04506905 | Safety, Tolerability, and Pharmacokinetics Study of Elpipodect (MK-8189) in Participants With Schizophrenia and Healthy Participants (MK-8189-011) | PHASE1 | COMPLETED | 63 | — | — | Aug 28, 2020 | Mar 22, 2022 | Apr 29, 2026 | 6 | United States |
| NCT02181803 | Elpipodect (MK-8189) Multiple Dose Study in Healthy Volunteers and Schizophrenia Participants (MK-8189-003) | PHASE1 | COMPLETED | 55 | — | — | Aug 5, 2014 | Apr 23, 2015 | Apr 29, 2026 | - | — |
The PANSS assesses the severity of schizophrenia symptoms through a 30-item clinician-rated inventory organized into a positive subscale (7 items), a negative subscale (7 items) and a general psychopathology subscale (16 items). For each item, symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranges from 30 (lowest total score) to 210 (highest total score). Higher and lower change scores reflect symptom worsening and improvement, respectively. Risperidone and placebo were active and inactive controls, respectively.
An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. Per protocol, events were assessed for the first 6 weeks of treatment.
An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. Per protocol, events were assessed for the first 6 weeks of 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.
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.
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.
An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced one or more AEs were reported.
An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study due to an AE were reported.
The number of participants with ≥1 AE is reported. 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.
The number of participants discontinuing from study treatment due to ≥1 AE is reported. 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.
C24hr was defined as the concentration of MK-8189 observed in plasma at the 24-hour nominal sampling time after administration of MK-8189. In participants receiving MK-8189, blood samples were collected pre-dose and 24 hours post-dose to estimate C24hr following MK-8189 administration. As specified by the protocol, C24hr was analyzed by part, dose and dosing schedule. Due to differing dosing schedules, some time points were not applicable for certain arms/doses as indicated by zero participants analyzed entered in the table. Per protocol, healthy participants (Part 3) and participants receiving placebo were excluded from C24 analysis.
AUC was defined as a measure of MK-8189 exposure that was calculated as the product of plasma drug concentration and time. The linear-up-log down rule was used to estimate AUC. Blood samples were collected pre-dose and up to 24 hours post-dose to estimate AUC(0-24hr) following MK-8189 administration. As specified by the protocol, AUC(0-24hr) was analyzed by part, dose and dosing schedule. Due to differing dosing schedules, some time points were not applicable for certain arms/doses as indicated by zero participants analyzed entered in the table. Per protocol, healthy participants (Part 3) and participants receiving placebo were excluded from AUC(0-24hr) analysis.
Cmax was defined as the maximum concentration of MK-8189 observed in plasma. Blood samples were collected pre-dose and up to 48 hours post-dose at multiple time points to estimate Cmax following MK-8189 administration. As specified by the protocol, Cmax was analyzed by part, dose and dosing schedule. Due to differing dosing schedules, some time points were not applicable for certain arms/doses as indicated by zero participants analyzed entered in the table. Per protocol, healthy participants (Part 3) and participants receiving placebo were excluded from Cmax analysis.
Tmax was defined as the time required post dose to reach a maximum plasma concentration of MK-8189. It was estimated as the actual sampling time at the highest MK-8189 plasma concentration. Blood samples were collected pre-dose and up to 48 hours post-dose at multiple time points to estimate Tmax following MK-8189 administration. As specified by the protocol, Tmax was analyzed by part, dose and dosing schedule. Due to differing dosing schedules, some time points were not applicable for certain arms/doses as indicated by zero participants analyzed entered in the table. Per protocol, healthy participants (Part 3) and participants receiving placebo were excluded from Tmax analysis.
t1/2 was defined as the time required to divide the MK-8189 plasma concentration by half after reaching pseudo-equilibrium. At least three quantifiable post-Cmax, terminal phase concentrations collected were used to calculate the apparent t1/2. Blood samples were collected pre-dose and up to 48 hours post-dose at multiple time points on Day 14 to estimate t1/2 following MK-8189 administration. As specified by the protocol, t1/2 was analyzed by part, dose and dosing schedule. Due to differing dosing schedules, the Day 14 timepoint was not applicable for certain arms/doses as indicated by zero participants analyzed entered in the table. Per protocol, healthy participants (Part 3) and participants receiving placebo were excluded from t1/2 analysis.
| Arm | Type | Description |
|---|---|---|
| Elpipodect 8 mg | EXPERIMENTAL | Participants received elpipodect 8 mg QD from Weeks 1 to 12, with 2 weeks of follow-up |
| Elpipodect 16 mg | EXPERIMENTAL | Participants received elpipodect 16 mg QD from Weeks 1 to 12, with 2 weeks of follow-up. |
| Elpipodect 24 mg | EXPERIMENTAL | Participants received elpipodect 24 mg QD from Weeks 1 to 12, with 2 weeks of follow-up. |
| Risperidone 6 mg | ACTIVE_COMPARATOR | Participants will be treated for a total of 12 weeks. Participants will receive risperidone 6 mg QD in the acute treatment period from Week 1-6 followed by risperidone 6 mg QD in the extension treatment period from Week 7-12. |
| Placebo and Elpipodect 24 mg | EXPERIMENTAL | Participants received placebo QD from Weeks 1 to 6 and elpipodect 24 mg from Weeks 7 to 12, with 2 weeks of follow-up. |
| Sequence 1: Elpipodect (Treatment A)→Moxifloxacin (Treatment B)→Placebo (Treatment C) | EXPERIMENTAL | 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. |
| Sequence 2: Moxifloxacin (Treatment B) →Placebo (Treatment C) →Elpipodect (Treatment A) | EXPERIMENTAL | 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. |
| Sequence 3: Placebo (Treatment C) →Elpipodect (Treatment A) →Moxifloxacin (Treatment B) | EXPERIMENTAL | 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. |
| Sequence 4: Moxifloxacin (Treatment B) →Elpipodect (Treatment A) → Placebo (Treatment C) | EXPERIMENTAL | 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. |
| Sequence 5: Elpipodect (Treatment A) →Placebo (Treatment C) →Moxifloxacin (Treatment B) | EXPERIMENTAL | 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. |
| Sequence 6: Placebo (Treatment C) →Moxifloxacin (Treatment B) → Elpipodect (Treatment A) | EXPERIMENTAL | 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. |
| Elpipodect Panel A | EXPERIMENTAL | Participants will receive elpipodect starting at 48 mg on Day 1 and 60 mg on Day 2. |
| Elpipodect Panel A-1 | EXPERIMENTAL | Participants will receive elpipodect 48 mg on Day 1 and 80 mg on Day 2. |
| Elpipodect Panel C | EXPERIMENTAL | Participants will receive elpipodect 48 mg on Days 1-2 and 80 mg on Day 3 based on safety and tolerability. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive MK-8189-matching placebo. |
| Part 1 (Panel A) Elpipodect | EXPERIMENTAL | Young adult participants with schizophrenia receive elpipodect titrated from 16 mg to 24 mg once daily (QD), orally, over a course of 7-day treatment. |
| Part 1 (Panel B) Elpipodect | EXPERIMENTAL | Young adult participants with schizophrenia receive elpipodect titrated up to 24 mg QD, orally, over a course of 7-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panel. |
| Part 1 (Panel C) Elpipodect | EXPERIMENTAL | Young adult participants with schizophrenia receive elpipodect titrated from 8 mg to 24 mg QD, orally, over a course of 7-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels. |
| Part 2 (Panel D) Elpipodect | EXPERIMENTAL | Elderly adult participants with schizophrenia receive elpipodect titrated from 8 mg to 24 mg QD, orally, over the course of a 13-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels. |
| Part 2 (Panel E) Elpipodect | EXPERIMENTAL | Elderly adult participants with schizophrenia receive elpipodect titrated from 16 mg to 24 mg QD, orally, over the course of 10-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels. |
| Part 2 (Panel F) Elpipodect | EXPERIMENTAL | Healthy elderly adult participants receive elpipodect titrated from 8 mg to 24 mg QD, orally, over the course of a 13-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels. |
| Part 2 (Panel G) Elpipodect | EXPERIMENTAL | Healthy elderly adult participants receive elpipodect titrated from 16 mg to 24 mg QD, orally, over the course of 10-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels. |
| Part 1 (Panels A, B, C) Placebo | PLACEBO_COMPARATOR | Oral tablets of dose-matched placebo to total daily dose of elpipodect. |
| Part 2 (Panels D, E, F, G) Placebo | PLACEBO_COMPARATOR | Oral tablets of dose-matched placebo to total daily dose of elpipodect. |
| Part 1 Panel A & B Elpipodect Monotherapy 2-40 mg: Schizophrenic | EXPERIMENTAL | Participants with schizophrenia will receive monotherapy of elpipodect in escalating doses starting at 2 mg once daily (QD) up to 40 mg QD, depending on safety and tolerability |
| Part 2 Panel C Elpipodect Add-on Therapy 2-20 mg: Schizophrenic | EXPERIMENTAL | Participants with schizophrenia will receive add-on therapy of elpipodect in escalating doses starting at 2 mg QD up to 20 mg QD, depending on safety and tolerability |
| Part 2 Panel C Elpipodect Add-on Therapy 4-20 mg: Schizophrenic | EXPERIMENTAL | Participants with schizophrenia will receive add-on therapy of elpipodect in escalating doses starting at 4 mg QD up to 20 mg QD, depending on safety and tolerability |
| Part 3 Panel D Elpipodect Monotherapy 2-16 mg: Healthy | EXPERIMENTAL | Healthy participants will receive monotherapy of elpipodect in escalating doses starting at 2 mg QD up to 16 mg QD, depending on safety and tolerability |
| Part 1 Panel A & B Placebo Monotherapy: Schizophrenic | PLACEBO_COMPARATOR | Participants with schizophrenia will receive dose-matched placebo to elpipodect monotherapy |
| Part 2 Panel C Placebo Add-on Therapy: Schizophrenic | PLACEBO_COMPARATOR | Participants with schizophrenia will receive dose-matched placebo to elpipodect add-on therapy |
| Part 3 Panel D Placebo Monotherapy: Healthy | PLACEBO_COMPARATOR | Healthy participants will receive dose-matched placebo to elpipodect monotherapy |
| Name | Type | Description |
|---|---|---|
| Elpipodect | DRUG | MK-8189 administered QD at a dose of 8 mg, 16 mg, or 24 mg via oral tablet. |
| Risperidone | DRUG | Risperidone administered QD at a dose of 6 mg via oral capsule. |
| Placebo to MK-8189 | DRUG | MK-8189-matching placebo administered QD via oral tablet. |
| Placebo to risperidone | DRUG | Risperidone-matching placebo administered QD via oral capsule. |
| Moxifloxacin | DRUG | Oral Tablet |
| Placebo | DRUG | Oral Tablet |
| Base Monotherapy | DRUG | For Part 2 only: participants need to be on monotherapy with an atypical antipsychotic medication (eg, Olanzapine, Quetiapine, Paliperidone, Asenapine, Iloperidone, Aripirprazole, Lurasidone, Risperidone \[not to exceed daily dose of 6 mg\], or Ziprasidone.) The participant should be on a stable and well tolerated treatment regimen for at least 2 months prior to screening. NOTE: Clozapine is not allowed. |
Inclusion Criteria: The main inclusion criteria include, but are not limited to the following: * Meet the diagnostic criteria for schizophrenia according to the DSM-5 * Have an illness duration for schizophrenia of at least 1 year * Be confirmed to be experiencing an acute episode of schizophrenia...