Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Preladenant, MK-3814, Adenosine 2a Antagonist
SCH 420814 · 8 trials · 9 indications
The "on" state is defined as the period of time during which a patient's symptoms of PD improve or disappear following treatment with L-dopa or dopamine agonists. The "off" state is defined as the period of time characterized by the return of symptoms (i..e. tremor, slowness, and rigidity) following treatment with L-dopa or dopamine agonists. Study participants reported their symptoms at half-hour intervals as "off", "on", or "asleep" on their daily diary for 3 days before randomization (baseline) and for the 3 days immediately before their Week 12 visit. The mean change from baseline in "off" time was based on a constrained longitudinal data analysis (cLDA) with treatment, time, and treatment-by-time interaction as fixed effects and subject as random effect.
The number of participants with Systolic Blood Pressure (SBP) ≥180 mmHg and 20 mmHg increase was reported. Participants lie supine at rest for 5 minutes, then have a single BP measurement taken (ie, 1 reading). Participants then stand for 3 minutes at rest, followed by a single BP measurement (1 reading) in the standing position.
The number of participants with Diastolic Blood Pressure (DBP) ≥105 mmHg and 15 mmHg increase was reported. Participants lie supine at rest for 5 minutes, then have a single BP measurement taken (ie, 1 reading). Participants then stand for 3 minutes at rest, followed by a single BP measurement (1 reading) in the standing position.
The percentage of participants with suicidality using the Columbia - Suicide Severity Rating Scale (C-SSRS) was reported. The C-SSR was used in this study only for the purpose of safety monitoring by measuring the incidence of different types of suicidality categories during treatment. The assessment was done by the nature of the responses, not by a numbered scale. Participants who reported at least one occurrence of suicidal behavior or suicidal ideation were counted as having experienced suicidality. Suicidal behavior included suicide attempt, aborted attempt, interrupted attempt, or preparatory behavior. Suicidal ideation included a wish to die or active suicidal thought with or without method, intent or plan.
The ESS is a self-administered questionnaire providing a measure of a person's general level of daytime sleepiness, or their average sleep propensity in daily life. The scale consists of 8 situations in which the participant rates their tendency to become sleepy on a scale of 0=no chance of dozing to 3=high chance of dozing. The overall score is the sum of the scores for the 8 situations for a minimum of 0 and a maximum of 24 with a higher score indicating greater sleepiness. The mean change from baseline in total EES was based on a cLDA with treatment, time, and treatment-by-time interaction as fixed effects and subject as random effect.
The "on" state is defined as the period of time during which a patient's symptoms of PD improve or disappear following treatment with L-dopa or dopamine agonists. The "off" state is defined as the period of time characterized by the return of symptoms (i..e. tremor, slowness, and rigidity) following treatment with L-dopa or dopamine agonists. Study participants reported their symptoms at half-hour intervals as "off", "on", or "asleep" on their daily diary for 3 days before randomization (baseline) and for the 3 days immediately before their Week-12 visit. The mean change from baseline in "off" time was based on a constrained longitudinal data analysis with treatment, time, and treatment-by-time interaction as fixed effects and subject as random effect.
The number of participants with Systolic Blood Pressure \>=180 mm Hg was reported.
The number of participants with Diastolic Blood Pressure \>=105 mm Hg was reported.
The number of participants with alanine aminotransferase \>=3 times the upper limit of normal and a \>=10% increase was reported.
The number of participants with aspartate aminotransferase \>=3 times the upper limit of normal and a \>=10% increase was reported.
The ESS is a self-administered questionnaire providing a measure of a person's general level of daytime sleepiness, or their average sleep propensity in daily life. The scale consists of 8 situations in which the participant rates their tendency to become sleepy on a scale of 0=no chance of dozing to 3=high chance of dozing. The overall score is the sum of the scores for the 8 situations for a minimum of 0 and a maximum of 24.
The "on" state is defined as the period of time during which a participant's symptoms of PD improve or disappear following treatment with levodopa (L-dopa) or dopamine agonists. The "off" state is defined as the period of time characterized by the return of symptoms (i..e. tremor, slowness, and rigidity) following treatment with L-dopa or dopamine agonists. Study participants reported their symptoms at half-hour intervals as "off", "on", or "asleep" on their daily diary for 3 days before randomization (baseline) and for the 3 days immediately before their Week-12 visit. The mean change from baseline in "off" time was based on a constrained longitudinal data analysis with treatment, time, and treatment-by-time interaction as fixed effects, and an unstructured covariance matrix was used to model the correlation among repeated measurements.
An adverse event (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 (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
An adverse event (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 (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure. A serious adverse event is an adverse event that that results in death, life threatening adverse event, permanent or significant disability / unfitness for work, hospital treatment (i.e., admission to hospital) or prolongation of a patient's length of stay, or congenital deformity or birth defect.
"Off" time refers to periods of inadequate control of Parkinson disease symptoms (worsening or presence of symptoms). For baseline and the 12 weeks treatment period, hours spent in the "off" state during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. Change from baseline in least squares (LS) means and pooled standard deviation (SD) were obtained from an analysis of covariance (ANCOVA) model with effect for treatment and baseline covariate. A negative change from baseline signifies less time spent in the "off" state.
For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of preladenant.
For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of preladenant.
Blood samples were taken at the following timepoints: pre-dose, 0.25, 0.50, 0.75, 1, 2, 4, 6, 12, 16, 24, 30, 36 and 48 hours postdose in order to determine the AUC0-∞ of preladenant
Blood samples were taken at the following timepoints: pre-dose, 0.25, 0.50, 0.75, 1, 2, 4, 6, 12, 16, 24, 30, 36 and 48 hours postdose in order to determine the AUC0-∞ of preladenant
Blood samples were taken at the following timepoints: pre-dose, 0.25, 0.50, 0.75, 1, 2, 4, 6, 12, 16, 24, 30, 36 and 48 hours postdose in order to determine the AUC0-∞ of preladenant
Dyskinesia was scored on a scale of 0 (absent), 1 (mild) , 2 (moderate), 3 (severe) and 4 (incapacitating) for seven body parts (face, neck, trunk, each arm and each leg) based on the worse dyskinesia noted during the entire measurement time. Scores were assessed at Hours 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0 and 8.0. The dyskinesia score was the sum of the scores for the seven body parts. The peak dyskinesia score was recorded for each participant regardless of what timepoint the score was achieved. The total possible score for an individual at each timepoint could range from 0 to 28 with higher scores indicating greater effects of the dyskinesia. The mean peak dyskinesia score was calculated using the individual peak values.
| Arm | Type | Description |
|---|---|---|
| Preladenant 2 mg | EXPERIMENTAL | Participants received 2 mg as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extension trial or return for a follow-up visit two (2) weeks later. |
| Preladenant 5 mg | EXPERIMENTAL | Participants received 5 mg as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extension trial or return for a follow-up visit two (2) weeks later. |
| Placebo | PLACEBO_COMPARATOR | Participants received preladenant-matching placebo as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extention trial or return for a follow-up visit two (2) weeks later. |
| Preladenant 10 mg | EXPERIMENTAL | Preladenant 10 mg tablet + placebo to rasagiline capsule in AM and preladenant 10 mg tablet in PM for 12 weeks |
| Rasagiline 1 mg | ACTIVE_COMPARATOR | Rasagiline 1 mg capsule + placebo to preladenant tablet in AM and placebo to preladenant tablet in PM for 12 weeks |
| Preladenant 5 mg BID | EXPERIMENTAL | Preladenant 5 mg twice daily (BID) given open-label for 36 weeks to participants with moderate to severe Parkinson's Disease who are on a long-term and stable L-dopa treatment regimen. |
| Preladenant 1 mg BID | EXPERIMENTAL | Participants received preladenant 1 mg twice daily (BID) during the 12-week treatment period. |
| Preladenant 2 mg BID | EXPERIMENTAL | Participants received preladenant 2 mg BID during the 12-week treatment period. |
| Preladenant 10 mg BID | EXPERIMENTAL | Participants received preladenant 10 mg BID during the 12-week treatment period. |
| Placebo BID | PLACEBO_COMPARATOR | Participants received preladenant matching placebo BID during the 12-week treatment period. |
| Mild Hepatic Impaired (HI) Part 1 | EXPERIMENTAL | Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1. |
| Healthy to Match Mild HI Part 1 | ACTIVE_COMPARATOR | Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1. |
| Moderate HI Part 2 | EXPERIMENTAL | Participants with moderate chronic liver disease enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1. |
| Healthy to Match Moderate HI Part 2 | ACTIVE_COMPARATOR | Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1. |
| Part 1: Severe Renal Impairment | EXPERIMENTAL | Participants with severe CRI, defined as creatinine clearance of \<30 mL/min/1.73 m\^2, were treated with a single tablet of 5 mg preladenant, administered orally |
| Part 2: Moderate Renal Impairment | EXPERIMENTAL | Participants with moderate CRI defined as creatinine clearance of ≥30 and \<50 mL/min/1.73 m\^2, were treated with a single tablet of 5 mg preladenant, administered orally |
| Part 2: Mild Renal Impairment | EXPERIMENTAL | Participants with mild CRI, defined as creatinine clearance of ≥50 and ≤80 mL/min/1.73m\^2, were treated with a single tablet of 5 mg preladenant, administered orally |
| Part 1: Normal Renal Function | EXPERIMENTAL | Participants with normal renal function, defined as creatinine clearance of \>80 mL/min/1.73 m\^2, were treated with a single tablet of 5 mg preladenant, administered orally |
| Part 2: Normal Renal Function | EXPERIMENTAL | Participants with normal renal function, defined as creatinine clearance of \>80 mL/min/1.73 m\^2, were treated with a single tablet of 5 mg preladenant, administered orally |
| SCH 420814 10 mg→SCH 420814 100 mg→Placebo | EXPERIMENTAL | Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose. |
| SCH 420814 100 mg→Placebo→ SCH 420814 10 mg | EXPERIMENTAL | Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose. |
| Placebo→SCH 420814 10 mg→SCH 420814 100 mg | EXPERIMENTAL | Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose. |
| SCH 420814 10 mg→ Placebo→ SCH 420814 100 mg | EXPERIMENTAL | Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose. |
| SCH 420814 100 mg→ SCH 420814 10 mg→Placebo | EXPERIMENTAL | Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose. |
| Placebo→ SCH 420814 100 mg→SCH 420814 10 mg | EXPERIMENTAL | Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose. |
| Name | Type | Description |
|---|---|---|
| Preladenant | DRUG | Preladenant 2 mg or 5 mg oral tablet taken twice daily |
| Placebo | DRUG | Preladenant-matching placebo oral tablet taken twice daily |
| Preladenant 2 mg tablet | DRUG | one 2 mg tablet orally twice daily |
| Preladenant 5 mg tablet | DRUG | one 5 mg tablet orally twice daily |
| Preladenant 10 mg tablet | DRUG | one 10 mg tablet orally twice daily |
| Placebo to Preladenant Tablet | DRUG | one tablet orally twice daily |
| Rasagiline 1 mg capsule | DRUG | one 1 mg capsule orally in AM |
| Placebo to Rasagiline capsule | DRUG | one capsule orally in AM |
| Placebo tablet to match Preladenant | DRUG | tablets taken orally BID |
| L-dopa | DRUG | Participants must receive L-dopa as part of their usual ongoing treatment for Parkinson's Disease. L-dopa is often administered concomitantly with a dopa decarboxylase inhibitor (e.g., carbidopa). |
| Other Parkinson's Disease treatments | DRUG | Participants may also receive other drugs as part of their usual ongoing treatment for Parkinson's Disease, such as dopamine agonists (e.g., pramipexole) and/or the catechol-O methyl transferase (COMT) inhibitor entacapone. |
| SCH 420814 10 mg | DRUG | one 10-mg capsule, orally, at hour 0 of treatment period |
| SCH 420814 100 mg | DRUG | single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period |
| Levodopa | DRUG | levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours |
| Carbidopa | DRUG | one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period |
Inclusion Criteria: * Each participant must have a diagnosis of idiopathic Parkinson's disease. * Each participant must have received prior therapy with L-dopa for approximately 1 or more years immediately before Screening and must continue to have a beneficial clinical response to L-dopa. * Each p...
Top 15 of 23 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Supernus Pharmaceuticals, Inc. | SUPN | 2 | PHASE3 | Onapgo (SPN-830) |
| Prothena Corp. Plc | PRTA | 3 | PHASE3 | Prasinezumab |
| Denali Therapeutics Inc. | DNLI | 1 | PHASE2 | BIIB122 |
| Bayer | BAYRY | 4 | PHASE3 | bemdaneprocel, AB-1005 |
| Biohaven Ltd. | BHVN | 1 | PHASE2 | BHV-8000 |
| AC Immune SA | ACIU | 2 | PHASE2 | ACI-7104.056 |
| Eli Lilly and Company | LLY | 4 | PHASE1 | LY3884961, LY4006896, LY3962681 |
| Gain Therapeutics, Inc. | GANX | 2 | PHASE2 | GT-02287 |
| Annovis Bio Inc | ANVS | 1 | PHASE2 | Buntanetap |
| Regeneron Pharmaceuticals, Inc. | REGN | 2 | PHASE1 | ALN-SNCA |
| MeiraGTx Holdings Plc | MGTX | 1 | PHASE1 | AAV-GAD |
| Serina Therapeutics, Inc. | SER | 1 | PHASE1 | SER-252 |
| Ardelyx, Inc. | ARDX | 1 | PHASE2 | Tenapanor |
| Hoffmann-La Roche | RHHBY | 1 | PHASE1 | RO7568282 |
| Merck & Co., Inc. | MRK | 1 | EARLY_PHASE1 | MK-0947 |
SCH 420814 is an investigational small molecule developed by Merck & Company, Inc. (MRK) for Parkinson disease. It has been studied in a Phase 1 clinical trial evaluating its acute effects on dyskinesia and parkinsonism in levodopa-treated participants. It is also referred to as SCH 420814 10 mg.
SCH 420814 was studied for its acute effects on dyskinesia and parkinsonism in participants with Parkinson disease who were already being treated with levodopa. The research focused on whether the drug could influence these levodopa-related motor complications in this patient population.
SCH 420814 is developed by Merck & Company, Inc., which trades under the ticker MRK. Merck sponsored the Phase 1 trial of the compound in Parkinson disease.
SCH 420814 is in Phase 1 development. It is an investigational drug and is not approved for any indication. One Phase 1 trial has been completed, and no trials are currently active.
SCH 420814 has been evaluated in one completed Phase 1 trial, NCT00845000, titled "Acute Effects of Preladenant (SCH 420814) on Dyskinesia and Parkinsonism in Levodopa Treated Participants (P05550)." The randomized, double-blind, controlled study enrolled 12 participants aged 18 years and older with Parkinson disease.