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| ID | Type | Description | Link |
|---|---|---|---|
| MK-3814-026 | Other Identifier | Merck |
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This study is to evaluate the efficacy of a range of preladenant doses compared with placebo in participants with moderate to severe Parkinson's disease (PD) experiencing motor fluctuations and receiving a stable dose of levodopa (L-dopa), as measured by "off" time. Participants will continue to receive their stable regimen of L-dopa plus any adjunct medications during the study as prescribed by their physician. Several classes of adjunct medications may be used, including Amantadine, anticholinergics, dopa decarboxylase inhibitors, and dopamine agonists.
Primary Hypothesis: At least the 10 mg twice daily dose of preladenant is superior to placebo as measured by the change from Baseline to Week 12 in the mean "off" time.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Preladenant 2 mg | Experimental | Participants will receive preladenant 2 mg taken orally twice daily (BID), one tablet in the morning and one tablet in the evening, for 12 weeks. |
|
| Preladenant 5 mg | Experimental | Participants will receive preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
|
| Preladenant 10 mg | Experimental | Participants will receive preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
|
| Placebo | Placebo Comparator | Participants will receive a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Preladenant | Drug | 2, 5, or 10 mg tablets taken orally twice daily (BID) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Mean "Off" Time (Hours Per Day) at Week 12 | 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. | Baseline and Week 12 |
| Number of Participants Who Experienced an Adverse Event (AE) | 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. | Up to 14 weeks |
| Number of Participants Who Discontinued Study Treatment Due to an AE | 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. | Up to 12 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With ≥30% Reduction in "Off" Time at Week 12 | The proportion of responders (≥30% Reduction in "Off" Time at Week 12) was analyzed using a generalized linear mixed model with baseline mean OFF time (hours/day) as a covariate and treatment-by-time interaction as a fixed effect, and an unstructured covariance matrix was used to model the correlation among repeated measurements. Responder rates for each treatment arm are presented as are differences from placebo with 95% confidence interval. |
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Inclusion Criteria:
therapeutic effect achieved with available anti-Parkinsonian treatment, for at least the 4 weeks immediately before randomization
treatment medications and within the 4 weeks immediately before Screening
- Must be experiencing a minimum of 2 hours/day of "off" time as estimated by the investigator
and supported by the symptom diary (Daily Diary) at the Diary Training Visit
- With or without the help of a caregiver, must be capable of maintaining an accurate and
complete symptom diary (Daily Diary) as assessed at the Diary Training Visit
- Must have results of Screening clinical laboratory tests (complete blood count [CBC], blood
chemistries, and urinalysis) within normal limits or clinically acceptable to the investigator at Screening
- Must have results of a physical examination within normal limits or clinically acceptable limits
to the investigator
gonadotropin [hCG]) at Screening and must agree to use a medically accepted method of contraception while receiving protocol-specified medication and for 2 weeks after stopping the medication
Exclusion Criteria:
of Mental Disorders IV Text Revision (DSM-IV-TR) criteria
- Must not be at imminent risk of self-harm or harm to others, in the investigator's opinion based on
clinical interview
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27632893 | Result | Hattori N, Kikuchi M, Adachi N, Hewitt D, Huyck S, Saito T. Adjunctive preladenant: A placebo-controlled, dose-finding study in Japanese patients with Parkinson's disease. Parkinsonism Relat Disord. 2016 Nov;32:73-79. doi: 10.1016/j.parkreldis.2016.08.020. Epub 2016 Aug 27. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Preladenant 2 mg | Participants received preladenant 2 mg taken orally twice daily (BID), one tablet in the morning and one tablet in the evening, for 12 weeks. |
| FG001 | Preladenant 5 mg | Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
| FG002 | Preladenant 10 mg | Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
| FG003 | Placebo | Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All Randomized Participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Preladenant 2 mg | Participants received preladenant 2 mg taken orally twice daily (BID), one tablet in the morning and one tablet in the evening, for 12 weeks. |
| BG001 | Preladenant 5 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Mean "Off" Time (Hours Per Day) at Week 12 | 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. | Full Analysis Set (FAS) population, which consisted of all randomized participants who received at least one dose of study treatment; had endpoint data subsequent to at least one dose of study treatment; and had baseline data for those analyses requiring baseline data. | Posted | Mean | Standard Deviation | Hours/Day | Baseline and Week 12 |
Up to 14 weeks
All Participants as Treated population, which included all participants who received at least one dose of study drug
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Preladenant 2 mg | Participants received preladenant 2 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CONSTIPATION | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C539997 | 2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine |
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| Placebo tablet to match Preladenant | Drug | tablets taken orally BID |
|
| Up to 12 Weeks |
| Change From Baseline in Mean "On" Time Without Troublesome Dyskinesias (Hours Per Day) at Week 12 | When a participant is "on" without dyskinesias, parkinsonian symptoms have dissipated and the participant is experiencing no uncontrollable extraneous movements. Study participants reported their parkinsonian symptoms at half-hour intervals as "off", "on without dyskinesia", "on with non-troublesome dyskinesia", "on with troublesome dyskinesia", or "asleep" on their daily diary for 3 days before randomization and for the 3 days immediately before their Week-12 visit. The mean change from baseline in "on without troublesome dyskinesia" 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. | Baseline and Week 12 |
| Subject Withdrew Consent |
|
| Lost to Follow-up |
|
| Non-compliance With Protocol |
|
| Did Not Meet Protocol Eligibility |
|
Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
| BG002 | Preladenant 10 mg | Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
| BG003 | Placebo | Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Preladenant 2 mg | Participants received preladenant 2 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
| OG001 | Preladenant 5 mg | Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
| OG002 | Preladenant 10 mg | Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
| OG003 | Placebo | Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. |
|
|
|
| Secondary | Percentage of Participants With ≥30% Reduction in "Off" Time at Week 12 | The proportion of responders (≥30% Reduction in "Off" Time at Week 12) was analyzed using a generalized linear mixed model with baseline mean OFF time (hours/day) as a covariate and treatment-by-time interaction as a fixed effect, and an unstructured covariance matrix was used to model the correlation among repeated measurements. Responder rates for each treatment arm are presented as are differences from placebo with 95% confidence interval. | Full Analysis Set (FAS) population, which consisted of all randomized participants who received at least one dose of study treatment; had endpoint data subsequent to at least one dose of study treatment; and had baseline data for those analyses requiring baseline data. | Posted | Number | Percentage of participants | Up to 12 Weeks |
|
|
|
|
| Secondary | Change From Baseline in Mean "On" Time Without Troublesome Dyskinesias (Hours Per Day) at Week 12 | When a participant is "on" without dyskinesias, parkinsonian symptoms have dissipated and the participant is experiencing no uncontrollable extraneous movements. Study participants reported their parkinsonian symptoms at half-hour intervals as "off", "on without dyskinesia", "on with non-troublesome dyskinesia", "on with troublesome dyskinesia", or "asleep" on their daily diary for 3 days before randomization and for the 3 days immediately before their Week-12 visit. The mean change from baseline in "on without troublesome dyskinesia" 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. | FAS population, which consisted of all randomized participants who received at least one dose of study treatment; had endpoint data subsequent to at least one dose of study treatment; and had baseline data for those analyses requiring baseline data. | Posted | Mean | Standard Deviation | Hours/Day | Baseline and Week 12 |
|
|
|
|
| Primary | Number of Participants Who Experienced an Adverse Event (AE) | 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. | All Participants as Treated population, which included all participants who received at least one dose of study drug | Posted | Number | Participants | Up to 14 weeks |
|
|
|
| Primary | Number of Participants Who Discontinued Study Treatment Due to an AE | 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. | All Participants as Treated population, which included all participants who received at least one dose of study drug | Posted | Number | Participants | Up to 12 Weeks |
|
|
|
| 9 |
| 111 |
| 19 |
| 111 |
| EG001 | Preladenant 5 mg | Participants received preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. | 5 | 113 | 23 | 113 |
| EG002 | Preladenant 10 mg | Participants received preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. | 7 | 113 | 25 | 113 |
| EG003 | Placebo | Participants received a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks. | 3 | 113 | 14 | 113 |
| INGUINAL HERNIA | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| LARGE INTESTINE POLYP | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| LOWER GASTROINTESTINAL HAEMORRHAGE | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| GAIT DISTURBANCE | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| DRUG-INDUCED LIVER INJURY | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
|
| CELLULITIS | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| PNEUMONIA | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| FEMUR FRACTURE | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| HEAT STROKE | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| SPINAL COMPRESSION FRACTURE | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| ULNA FRACTURE | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| JAW CYST | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| COLON CANCER | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
|
| METASTASES TO LYMPH NODES | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
|
| PARKINSON'S DISEASE | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| IMPULSE-CONTROL DISORDER | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| CYSTITIS HAEMORRHAGIC | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| URINARY RETENTION | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| ACTIVITIES OF DAILY LIVING IMPAIRED | Social circumstances | MedDRA 16.0 | Systematic Assessment |
|
| NASOPHARYNGITIS | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| FALL | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| DYSKINESIA | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including, without limitation, slides and texts of oral or other public presentations and texts of any transmission through any electronic media, eg, any computer access system such as the Internet, World Wide Web, etc) that report any results of the trial.
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| Difference in proportions of responders |
| 5.7 |
| 2-Sided |
| 95 |
| -7.73 |
| 18.81 |
| Superiority or Other |
| A generalized linear mixed model | 0.508 | Difference in proportions of responders | -4.9 | 2-Sided | 95 | -17.78 | 7.97 | Superiority or Other |
| Difference in Least Squares Mean |
| 0.5 |
| 2-Sided |
| 95 |
| -0.23 |
| 1.19 |
| Superiority or Other |
| Constrained longitudinal data analysis | 0.2021 | Difference in Least Squares Mean | 0.5 | 2-Sided | 95 | -0.25 | 1.19 | Superiority or Other |