Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Elpipodect · 10 trials · 6 indications
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.
The LSM change from baseline at week 4 was assessed for PANSS total score. The PANSS assesses the severity of schizophrenia symptoms through a clinician-rated inventory of 30 items organized in 3 subscales: 1) positive subscale (7 items); 2) negative subscale (7 items); and 3) general psychopathology subscale (16 items). For each item, symptoms are scored from 1 (absent) to 7 (extreme) and sum to a total PANSS score (range: 30-210). Higher scores reflect more severe symptoms of schizophrenia. Further, reduced symptom severity over time is reflected by decreases in score.
The percentage of participants experiencing an AE was assessed. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
The percentage of participants discontinuing study treatment due to an AE was assessed. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
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.
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.
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 can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Results are reported according to 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Results are reported according to dose.
Blood samples will be collected to determine the AUC0-24 of elpipodect.
Blood samples will be collected to determine the AUClast of elpipodect.
Blood samples will be collected to determine the AUC0-inf of elpipodect.
Blood samples will be collected to determine the Cmax of elpipodect.
Blood samples will be collected to determine the t1/2 of elpipodect.
Blood samples will be collected to determine the Tmax of elpipodect.
Urine samples will be collected to determine the Ae of elpipodect
Urine samples will be collected to determine the %dose of elpipodect
Feces samples will be collected to determine the Ae of elpipodect.
Feces samples will be collected to determine the %dose of elpipodect.
Blood samples will be collected to determine the metabolites of elpipodect.
Urine samples will be collected to determine the metabolites of elpipodect.
Feces samples will be collected to determine the metabolites of elpipodect.
AUC0-inf is a measure of the total amount of drug in the plasma from the dose administration extrapolated to infinity. Blood samples collected pre and post-dose at multiple timepoints were used to estimate AUC0-inf following MK-8189 administration. Geometric least-squares mean and confidence intervals for AUC0-inf were calculated using a linear fixed effects model performed on natural log-transformed values.
Cmax is the maximum concentration of MK-8189 observed in plasma. Blood samples collected pre and post-dose at multiple timepoints were used to estimate Cmax following MK-8189 administration. Geometric least-squares mean and confidence intervals of Cmax were calculated using a linear fixed effects model performed on natural log-transformed values.
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. |
| Elpipodect | EXPERIMENTAL | Participants receive elpipodect (4 mg controlled release \[CR\] oral tablet\[s\]) in combination with placebo matching risperidone (oral capsule\[s\]) once daily (QD) for 4 weeks. Over the initial 7 treatment days, elpipodect is titrated from 4 mg to 12 mg as follows: 4 mg (1 tablet; Day 1); 8 mg (2 tablets; Day 4); and 12 mg (3 tablets; Day 7). Placebo matching risperidone is also titrated as follows: 1 capsule (Day 1), 2 capsules (Day 4), and 3 capsules (Day 7). After Day 7, elpipodect is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks. |
| Risperidone | ACTIVE_COMPARATOR | Participants receive risperidone (2 mg oral capsule\[s\]) in combination with placebo matching elpipodect (oral tablet\[s\]), QD for 4 weeks. Over the initial 7 treatment days, risperidone is titrated from 2 mg to 6 mg as follows: 2 mg (1 capsule; Day 1); 4 mg (2 capsules; Day 4); and 6 mg (3 capsules; Day 7). Placebo matching elpipodect is also titrated as follows: 1 tablet (Day 1), 2 tablets (Day 4), and 3 tablets (Day 7). After Day 7, risperidone is maintained at 6 mg (3 capsules) in combination with placebo matching elpipodect (3 tablets), QD for 3 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants receive both placebo matching elpipodect (oral tablet\[s\]) as well as placebo matching Risperidone (oral capsule\[s\]), QD for 4 weeks. Over the initial 7 treatment days, placebo matching both elpipodect and risperidone are respectively titrated as follows: 1 tablet/1 capsule (Day 1); 2 tablets/2 capsules (Day 4); and 3 tablets/3 capsules (Day 7). After Day 7, placebo matching both elpipodect and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks. |
| Panel A: 24 mg Elpipodect | EXPERIMENTAL | Participants received 24 mg elpipodect once daily (QD) for 14 days. |
| Panel B: 16 & 24 mg Elpipodect | EXPERIMENTAL | Participants received 16 mg elpipodect QD on Days 1 to 3 and 24 mg MK-8189 QD on Days 4 to 14. |
| Panel C: 8, 16, & 24 mg Elpipodect | EXPERIMENTAL | Participants received 8 mg elpipodect Day 1, 16 mg on Day 2 ,and 24 mg on QD Days 3 to 14. |
| Panel C: Placebo | PLACEBO_COMPARATOR | Participants received Panel C MK-8189-matching placebo QD for 14 days. |
| Panel A: Placebo | PLACEBO_COMPARATOR | Participants received Panel A MK-8189-matching placebo QD for 14 days. |
| Panel B: Placebo | PLACEBO_COMPARATOR | Participants received Panel B MK-8189-matching placebo for 14 days. |
| 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. |
| Carbon-14 radiolabeled [14C] Elpipodect | EXPERIMENTAL | Participants receive a dose of 4.5-mg immediate release (IR) (\~ 50 μCi) orally on Day 1. |
| Moderate Hepatic Impairment Participants | EXPERIMENTAL | Participants with hepatic impairment will receive a single dose of elpipodect 4 mg orally on Day 1. |
| Healthy Participants | EXPERIMENTAL | Healthy participants will receive a single dose of MK-8189 4 mg orally on Day 1. |
| 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. |
| Placebo matching MK-8189 | DRUG | Oral placebo tablet(s) matching the MK-8189 tablet, administered QD. |
| Placebo matching risperidone | DRUG | Oral placebo capsule(s) matching the risperidone capsule, administered QD. |
| Placebo | DRUG | Oral Tablet |
| Moxifloxacin | DRUG | Oral Tablet |
| [14C]Elpipodect | DRUG | Oral administration |
| 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...
Elpipodect is an investigational small molecule being developed for neurology conditions, including schizophrenia, Alzheimer's disease, bipolar I disorder, and hepatic impairment. It is currently in Phase 1 clinical development and has not been approved by the FDA.
Elpipodect is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK. The drug is currently in Phase 1 clinical trials.
Elpipodect is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. All five clinical trials for Elpipodect have been completed.
Elpipodect has completed Phase 1 trials, including NCT02181803 and NCT04506905 in schizophrenia, NCT05227118 in Alzheimer's disease, and NCT05406440 in schizophrenia. These trials studied safety, tolerability, and pharmacokinetics.
Yes, Elpipodect is also known as MK-8189. Clinical trials for Elpipodect, such as NCT02181803 and NCT04506905, use the MK-8189 designation in their titles.