Parkinson Disease
Conditions
Brief summary
This is a one year, 2-part study to determine the efficacy and safety of preladenant, an adenosine type 2a (A2a) receptor antagonist. The purpose of Part 1 (first 26 weeks) is to determine if preladenant is effective in the treatment of early Parkinson's Disease. The purpose of Part 2 (second 26 weeks) is to determine if preladenant is safe and well tolerated. The primary efficacy hypothesis is that at least the 10 mg twice daily dose of preladenant is superior to placebo as measured by the change from Baseline to Week 26 in the sum of Unified Parkinson's Disease Rating Scale (UPDRS) Parts 2 and 3 scores (UPDRS2+3).
Interventions
Preladenant 2 mg oral tablet taken twice daily
Preladenant 5 mg oral tablet taken twice daily
Preladenant 10 mg oral tablet taken twice daily
Rasagiline 1 mg oral capsule taken once daily
DRUGPlacebo for Rasagiline 1 mg capsule
Placebo for rasagiline 1 mg oral capsule taken once daily
DRUGPlacebo for Preladenant
Placebo for preladenant 2 mg, 5 mg, or 10 mg oral tablet taken twice daily
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Has a diagnosis of idiopathic PD for \< 5 years. * If receiving amantadine and/or anticholinergics, must have been on a stable regimen of treatment for at least the 5 weeks immediately before Screening. (Note: Participants who are not taking any medications for PD are permitted to enroll in this trial.) * Must have a UPDRS Part 3 score of ≥10, a Hoehn and Yahr Stage ≤3, be ≥30 to ≤85 years of age, and have results of Screening clinical laboratory tests drawn within 5 weeks prior to randomization, clinically acceptable to the investigator, and not within the parameters specified for exclusion. * If sexually active or plan to be sexually active, must agree to use a highly effective method of birth control while the participant is in the study and for 2 weeks after the last dose of study drug. A male participant must also not donate sperm during the trial and within 2 weeks after the last dose of study drug.
Exclusion criteria
* Must not have a form of drug-induced or atypical Parkinsonism, cognitive impairment (ie, Montreal Cognitive Assessment \[MoCA\] score \<22), bipolar disorder, untreated major depressive disorder, schizophrenia, or other psychotic disorder; history of exposure to a known neurotoxin, or any neurological features not consistent with the diagnosis of PD as assessed by the investigator. * Must not have had surgery for PD. * Must not have a history of repeated strokes with stepwise progression of Parkinsonism or head injuries, or a stroke within 6 months of screening; poorly controlled diabetes; abnormal renal function; or a severe or ongoing unstable medical condition. * Must not have failed to show a therapeutic response if a diagnostic levodopa (L dopa) challenge had been done with a large test dose (\>500 mg) of L dopa (if malabsorption excluded), or failed to respond to an adequate previous treatment with dopaminergic therapy. * Must not have been treated with L dopa or dopamine agonists for 30 days or more. A participant who has been treated with L-dopa or dopamine agonists for \<30 days will be allowed to enter the study. These participants must stop taking dopaminergic medication 30 days prior to Randomization. * Must not be at imminent risk of self-harm or harm to others. * Must not have elevated blood pressure (BP) (systolic BP ≥150 mm Hg or diastolic BP ≥95 mm Hg) that cannot be adequately controlled with antihypertensive medication, as demonstrated by 2 BP measurements meeting acceptable BP criterion at consecutive scheduled or unscheduled visits between Screening and Randomization (a 5-6 week period), one of which must be the Randomization visit. * Must not have had any clinically significant cardiovascular event or procedure for 6 months prior to Randomization, including, but not limited to, myocardial infarction, angioplasty, unstable angina, or heart failure; and a participant must not have heart failure staged New York Heart Association Class III or IV. * Must not have an alanine aminotransferase (ALT) or aspartate amino transferase (AST) ≥ 3 x the upper limit of normal (ULN) or total bilirubin (T BIL) ≥ 1.5 x ULN. * Must not have active serologically-confirmed hepatic dysfunction (defined as viral infection \[Hepatitis B, C, or E; Epstein-Barr virus (EBV)\]; cytomegalovirus \[CMV\] or a history of diagnosis of drug- or alcohol-induced hepatic toxicity or frank hepatitis, or a history of diagnosis of drug- or alcohol-induced hepatic toxicity or frank hepatitis.) * Must not have a history within the past 5 years of a primary or recurrent malignant disease with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or in situ prostate cancer with a normal prostate-specific antigen (PSA) post resection. * Must not have received certain prespecified medications or ingested high tyramine-containing aged cheeses (eg, Stilton) for a prespecified time window before the trial, during the trial, and for 2 weeks after the trial. * Must not have an average daily consumption of more than three 4 ounce glasses (118 mL) of wine or the equivalent. * Must not have a severe or ongoing unstable medical condition (eg, any form of clinically significant cardiac disease, symptomatic orthostatic hypotension, seizures, or alcohol/drug dependence.) * Must not have allergy/sensitivity to investigational product(s) or its/their excipients. * Must not be breast-feeding, considering breast-feeding, pregnant or intending to become pregnant. * Must not have used preladenant ever, or any investigational drugs within 90 days immediately before screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) in Part 1 | Day 1 to Week 26 | 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. |
| Number of Participants With Adverse Events (AEs) in Part 2 | Week 27 to Week 52 | 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. |
| Number of Participants Who Discontinued Study Due to an AE in Part 2 | Week 27 to Week 52 | 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 (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. |
| Change From Baseline in the Sum of Unified Parkinson's Disease Rating Scale Parts 2 and 3 Scores (UPDRS2+3) | Baseline and Week 26 | The UPDRS is a clinician based rating scale used to measure motor impairments and disability. The UPDRS assesses six features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the participant. The UPDRS Part 2 is the Activities of Daily Living (ADL) score and can range from 0-52 as determined by the physician. The UPDRS Part 3 is the Motor Examination (Total Motor Score \[TMS\]) and is defined as the total score, ranging from 0-108 as determined by the physician, of the tests given in the motor examination section. The combined scores of Parts 2 and 3 can range from 0-160 with the higher score indicating the worse condition. Change from baseline was analyzed using a constrained longitudinal analysis (cLDA) model with treatment, time, strata and treatment-by-time interaction as fixed effects and participant as a random effect. |
| Number of Participants Who Discontinued Study Due to an AE in Part 1 | Day 1 to Week 26 | 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 (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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the UPDRS Part 2 Score (Activities of Daily Living [ADL]) | Baseline and Week 26 | The UPDRS is a clinician based rating scale used to measure motor impairments and disability. The UPDRS assesses six features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the participant. The UPDRS Part 2 is the Activities of Daily Living (ADL) score and can range from 0-52 as determined by the physician with the higher score indicating the worse condition. Change from baseline was analyzed using a cLDA model with treatment, time, strata and treatment-by-time interaction as fixed effects and participant as a random effect. |
| Percentage of Responders (Participants With a ≥20% Improvement in UPDRS2+3) | Baseline and Week 26 | UPDRS is a clinician based rating scale used to measure motor impairments and disability; it assesses 6 features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the participant. UPDRS Part 2 is Activities of Daily Living score and ranges from 0-52. UPDRS Part 3 is Motor Examination and ranges from 0-108. The combined scores of Parts 2 and 3 can range from 0-160 with the higher score indicating the worse condition. A Responder is defined as a participant with at least 20% improvement in UPDRS2+3 from Baseline to Week 26 (End of Part 1 Treatment); a participant with at least a 20% decrease from Baseline score in UPDRS2+3 is defined as a responder. The proportion of Responders was analyzed using a generalized linear mixed model with treatment effect, strata and Baseline UPDRS2+3 as a covariate, and treatment-by-time interaction as fixed effects and subject as random effect. |
Participant flow
Recruitment details
Participants with a diagnosis of idiopathic PD for less than 5 years were selected to participate in this study.
Pre-assignment details
In Part 1, participants were randomized to one of five treatment groups and treated for 26 weeks. In Part 2, which was conducted for an additional 26 weeks, participants continued taking the same study treatment from Part 1, except for placebo participants who were re-assigned to receive preladenant 5 mg twice daily.
Participants by arm
| Arm | Count |
|---|---|
| Preladenant 2 mg Participants received preladenant 2 mg oral tablet and placebo for rasagiline in the AM followed by preladenant 2 mg oral tablet in PM for 26 weeks (Part 1) and then for another 26 weeks (Part 2). | 204 |
| Preladenant 5 mg Participants received preladenant 5 mg oral tablet and placebo for rasagiline in the AM followed by preladenant 5 mg in the PM for 26 weeks (Part 1) and then for another 26 weeks (Part 2). | 204 |
| Preladenant 10 mg Participants received preladenant 10 mg oral tablet and placebo for rasagiline in the AM followed by preladenant 10 mg in the PM for 26 weeks (Part 1) and then for another 26 weeks (Part 2). | 206 |
| Placebo Participants received placebo for preladenant and placebo for rasagiline in the AM followed by placebo for preladenant in the PM for 26 weeks (Part 1); preladenant 5 mg was taken twice daily for 26 weeks (Part 2). | 204 |
| Rasagiline Participants received rasagiline 1 mg oral capsule and placebo for preladenant in the AM followed by placebo for preladenant in PM for 26 weeks (Part 1) and then for another 26 weeks (Part 2). | 204 |
| Total | 1,022 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Part I | Administrative | 2 | 2 | 2 | 0 | 0 |
| Part I | Adverse Event | 13 | 8 | 18 | 7 | 6 |
| Part I | Did Not Meet Protocol Eligibility | 3 | 1 | 2 | 1 | 3 |
| Part I | Did Not Receive Treatment | 4 | 2 | 2 | 6 | 1 |
| Part I | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 |
| Part I | Non-Compliance with Protocol | 2 | 1 | 3 | 3 | 2 |
| Part I | Treatment Failure | 3 | 0 | 3 | 1 | 2 |
| Part I | Withdrawal by Subject | 11 | 13 | 8 | 8 | 9 |
| Part II | Administrative | 43 | 49 | 36 | 38 | 46 |
| Part II | Adverse Event | 7 | 6 | 8 | 3 | 4 |
| Part II | Lost to Follow-up | 1 | 0 | 0 | 0 | 1 |
| Part II | Non-Compliance with Protocol | 0 | 1 | 0 | 2 | 0 |
| Part II | Treatment Failure | 0 | 1 | 2 | 0 | 1 |
| Part II | Withdrawal by Subject | 8 | 4 | 12 | 7 | 3 |
Baseline characteristics
| Characteristic | Preladenant 2 mg | Preladenant 5 mg | Preladenant 10 mg | Placebo | Rasagiline | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 63.0 Years STANDARD_DEVIATION 10.5 | 62.3 Years STANDARD_DEVIATION 10.2 | 63.8 Years STANDARD_DEVIATION 11.1 | 63.3 Years STANDARD_DEVIATION 10 | 62.9 Years STANDARD_DEVIATION 10.2 | 63.1 Years STANDARD_DEVIATION 10.4 |
| Sex: Female, Male Female | 78 Participants | 90 Participants | 90 Participants | 82 Participants | 85 Participants | 425 Participants |
| Sex: Female, Male Male | 126 Participants | 114 Participants | 116 Participants | 122 Participants | 119 Participants | 597 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 200 | 39 / 202 | 40 / 204 | 36 / 198 | 34 / 203 | 18 / 166 | 22 / 177 | 17 / 167 | 16 / 177 | 19 / 181 |
| serious Total, serious adverse events | 4 / 200 | 5 / 202 | 8 / 204 | 3 / 198 | 9 / 203 | 7 / 166 | 1 / 177 | 8 / 167 | 4 / 177 | 8 / 181 |
Outcome results
Primary
Change From Baseline in the Sum of Unified Parkinson's Disease Rating Scale Parts 2 and 3 Scores (UPDRS2+3)
The UPDRS is a clinician based rating scale used to measure motor impairments and disability. The UPDRS assesses six features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the participant. The UPDRS Part 2 is the Activities of Daily Living (ADL) score and can range from 0-52 as determined by the physician. The UPDRS Part 3 is the Motor Examination (Total Motor Score \[TMS\]) and is defined as the total score, ranging from 0-108 as determined by the physician, of the tests given in the motor examination section. The combined scores of Parts 2 and 3 can range from 0-160 with the higher score indicating the worse condition. Change from baseline was analyzed using a constrained longitudinal analysis (cLDA) model with treatment, time, strata and treatment-by-time interaction as fixed effects and participant as a random effect.
Time frame: Baseline and Week 26
Population: Full Analysis Set (FAS): All randomized and treated participants with at least one post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preladenant 2 mg (Part 1) | Change From Baseline in the Sum of Unified Parkinson's Disease Rating Scale Parts 2 and 3 Scores (UPDRS2+3) | 0.3 Score on a Scale | Standard Error 0.63 |
| Preladenant 5 mg (Part 1) | Change From Baseline in the Sum of Unified Parkinson's Disease Rating Scale Parts 2 and 3 Scores (UPDRS2+3) | -1.0 Score on a Scale | Standard Error 0.6 |
| Preladenant 10 mg (Part 1) | Change From Baseline in the Sum of Unified Parkinson's Disease Rating Scale Parts 2 and 3 Scores (UPDRS2+3) | -1.8 Score on a Scale | Standard Error 0.61 |
| Placebo (Part 1) | Change From Baseline in the Sum of Unified Parkinson's Disease Rating Scale Parts 2 and 3 Scores (UPDRS2+3) | -2.2 Score on a Scale | Standard Error 0.61 |
| Rasagiline (Part 1) | Change From Baseline in the Sum of Unified Parkinson's Disease Rating Scale Parts 2 and 3 Scores (UPDRS2+3) | -1.9 Score on a Scale | Standard Error 0.61 |
Comparison: Preladenant 2 mg (Part 1) vs Placebo (Part 1)p-value: 0.003395% CI: [0.86, 4.3]constrained longitudinal analysis
Comparison: Preladenant 5 mg (Part 1) vs Placebo (Part 1)p-value: 0.138295% CI: [-0.41, 2.94]constrained longitudinal analysis
Comparison: Preladenant 10 mg (Part 1) vs Placebo (Part 1)p-value: 0.637895% CI: [-1.29, 2.11]constrained longitudinal analysis
Comparison: Rasagiline (Part 1) vs Placebo (Part 1)p-value: 0.692395% CI: [-1.35, 2.03]constrained longitudinal analysis
Primary
Number of Participants Who Discontinued Study Due to an AE in Part 1
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 (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.
Time frame: Day 1 to Week 26
Population: All Participants as Treated: All participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Preladenant 2 mg (Part 1) | Number of Participants Who Discontinued Study Due to an AE in Part 1 | 13 Participants |
| Preladenant 5 mg (Part 1) | Number of Participants Who Discontinued Study Due to an AE in Part 1 | 8 Participants |
| Preladenant 10 mg (Part 1) | Number of Participants Who Discontinued Study Due to an AE in Part 1 | 20 Participants |
| Placebo (Part 1) | Number of Participants Who Discontinued Study Due to an AE in Part 1 | 8 Participants |
| Rasagiline (Part 1) | Number of Participants Who Discontinued Study Due to an AE in Part 1 | 6 Participants |
Primary
Number of Participants Who Discontinued Study Due to an AE in Part 2
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 (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.
Time frame: Week 27 to Week 52
Population: All Participants as Treated (APaT): All participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Preladenant 2 mg (Part 1) | Number of Participants Who Discontinued Study Due to an AE in Part 2 | 7 Participants |
| Preladenant 5 mg (Part 1) | Number of Participants Who Discontinued Study Due to an AE in Part 2 | 5 Participants |
| Preladenant 10 mg (Part 1) | Number of Participants Who Discontinued Study Due to an AE in Part 2 | 8 Participants |
| Placebo (Part 1) | Number of Participants Who Discontinued Study Due to an AE in Part 2 | 3 Participants |
| Rasagiline (Part 1) | Number of Participants Who Discontinued Study Due to an AE in Part 2 | 4 Participants |
Primary
Number of Participants With Adverse Events (AEs) in Part 1
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.
Time frame: Day 1 to Week 26
Population: All Participants as Treated: All participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Preladenant 2 mg (Part 1) | Number of Participants With Adverse Events (AEs) in Part 1 | 108 Participants |
| Preladenant 5 mg (Part 1) | Number of Participants With Adverse Events (AEs) in Part 1 | 110 Participants |
| Preladenant 10 mg (Part 1) | Number of Participants With Adverse Events (AEs) in Part 1 | 121 Participants |
| Placebo (Part 1) | Number of Participants With Adverse Events (AEs) in Part 1 | 102 Participants |
| Rasagiline (Part 1) | Number of Participants With Adverse Events (AEs) in Part 1 | 105 Participants |
Primary
Number of Participants With Adverse Events (AEs) in Part 2
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.
Time frame: Week 27 to Week 52
Population: All Participants as Treated: All participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Preladenant 2 mg (Part 1) | Number of Participants With Adverse Events (AEs) in Part 2 | 116 Participants |
| Preladenant 5 mg (Part 1) | Number of Participants With Adverse Events (AEs) in Part 2 | 120 Participants |
| Preladenant 10 mg (Part 1) | Number of Participants With Adverse Events (AEs) in Part 2 | 113 Participants |
| Placebo (Part 1) | Number of Participants With Adverse Events (AEs) in Part 2 | 120 Participants |
| Rasagiline (Part 1) | Number of Participants With Adverse Events (AEs) in Part 2 | 119 Participants |
Secondary
Change From Baseline in the UPDRS Part 2 Score (Activities of Daily Living [ADL])
The UPDRS is a clinician based rating scale used to measure motor impairments and disability. The UPDRS assesses six features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the participant. The UPDRS Part 2 is the Activities of Daily Living (ADL) score and can range from 0-52 as determined by the physician with the higher score indicating the worse condition. Change from baseline was analyzed using a cLDA model with treatment, time, strata and treatment-by-time interaction as fixed effects and participant as a random effect.
Time frame: Baseline and Week 26
Population: Full Analysis Set (FAS): All randomized and treated participants with at least one post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preladenant 2 mg (Part 1) | Change From Baseline in the UPDRS Part 2 Score (Activities of Daily Living [ADL]) | 0.30 Score on a Scale | Standard Error 0.22 |
| Preladenant 5 mg (Part 1) | Change From Baseline in the UPDRS Part 2 Score (Activities of Daily Living [ADL]) | 0.10 Score on a Scale | Standard Error 0.21 |
| Preladenant 10 mg (Part 1) | Change From Baseline in the UPDRS Part 2 Score (Activities of Daily Living [ADL]) | -0.20 Score on a Scale | Standard Error 0.21 |
| Placebo (Part 1) | Change From Baseline in the UPDRS Part 2 Score (Activities of Daily Living [ADL]) | -0.40 Score on a Scale | Standard Error 0.21 |
| Rasagiline (Part 1) | Change From Baseline in the UPDRS Part 2 Score (Activities of Daily Living [ADL]) | -0.20 Score on a Scale | Standard Error 0.21 |
Comparison: Preladenant 2 mg (Part 1) vs Placebo (Part 1)p-value: 0.023595% CI: [0.09, 1.27]constrained longitudinal analysis
Comparison: Preladenant 5 mg (Part 1) vs Placebo (Part 1)p-value: 0.109395% CI: [-0.11, 1.04]constrained longitudinal analysis
Comparison: Preladenant 10 mg (Part 1) vs Placebo (Part 1)p-value: 0.575695% CI: [-0.42, 0.75]constrained longitudinal analysis
Comparison: Rasagiline (Part 1) vs Placebo (Part 1)p-value: 0.665795% CI: [-0.45, 0.7]constrained longitudinal analysis
Secondary
Percentage of Responders (Participants With a ≥20% Improvement in UPDRS2+3)
UPDRS is a clinician based rating scale used to measure motor impairments and disability; it assesses 6 features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the participant. UPDRS Part 2 is Activities of Daily Living score and ranges from 0-52. UPDRS Part 3 is Motor Examination and ranges from 0-108. The combined scores of Parts 2 and 3 can range from 0-160 with the higher score indicating the worse condition. A Responder is defined as a participant with at least 20% improvement in UPDRS2+3 from Baseline to Week 26 (End of Part 1 Treatment); a participant with at least a 20% decrease from Baseline score in UPDRS2+3 is defined as a responder. The proportion of Responders was analyzed using a generalized linear mixed model with treatment effect, strata and Baseline UPDRS2+3 as a covariate, and treatment-by-time interaction as fixed effects and subject as random effect.
Time frame: Baseline and Week 26
Population: Full Analysis Set (FAS): All randomized and treated participants with at least one post-baseline value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Preladenant 2 mg (Part 1) | Percentage of Responders (Participants With a ≥20% Improvement in UPDRS2+3) | 25.90 Percentage of Responders |
| Preladenant 5 mg (Part 1) | Percentage of Responders (Participants With a ≥20% Improvement in UPDRS2+3) | 29.50 Percentage of Responders |
| Preladenant 10 mg (Part 1) | Percentage of Responders (Participants With a ≥20% Improvement in UPDRS2+3) | 31.50 Percentage of Responders |
| Placebo (Part 1) | Percentage of Responders (Participants With a ≥20% Improvement in UPDRS2+3) | 35.20 Percentage of Responders |
| Rasagiline (Part 1) | Percentage of Responders (Participants With a ≥20% Improvement in UPDRS2+3) | 33.10 Percentage of Responders |
Comparison: Preladenant 2 mg (Part 1) vs Placebo (Part 1)p-value: 0.078595% CI: [-21, 1.82]generalized linear mixed model
Comparison: Preladenant 5 mg (Part 1) vs Placebo (Part 1)p-value: 0.273595% CI: [-17.6, 5.05]generalized linear mixed model
Comparison: Preladenant 10 mg (Part 1) vs Placebo (Part 1)p-value: 0.482395% CI: [-15.2, 7.99]generalized linear mixed model
Comparison: Rasagiline (Part 1) vs Placebo (Part 1)p-value: 0.682795% CI: [-13.9, 9.24]generalized linear mixed model