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This study will be conducted in subjects with established Parkinson's disease in 2 parts. Part A will examine the tolerability, safety, and pharmacokinetics of AZ-009 dose escalation ; and Part B will assess the tolerability, safety, pharmacokinetics, and pharmacodynamics of AZ-009 compared with placebo in a crossover design
This study will be conducted in subjects with established Parkinson's disease in 2 parts.
Part A will examine the tolerability, safety, and pharmacokinetics of daily doses of AZ-009 for 5 days followed by 3 doses on each of days 6 and 7 in dose escalation through 3 cohorts
Part B will assess the tolerability, safety, pharmacokinetics, and pharmacodynamics of AZ-009 compared with placebo in subjects with established Parkinson's disease experiencing regular OFF episodes
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A-1a | Experimental | Part A, Arm 1 (active), Dose 1 (009-A1) |
|
| A-2a | Experimental | Part A, Arm 2 (active), Dose 2 (009-A2) |
|
| A-3a | Experimental | Part A, Arm 3 (active), Dose 3 (009-A3) |
|
| A-0p | Placebo Comparator | Part A, placebo comparator in all 3 arms, placebo dose (009-A0) |
|
| B-1 (009-B3 -> 009-B0) | Experimental | Crossover (active to placebo) |
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| B-1 (009-B0 -> 009-B3) | Experimental | Crossover (placebo to active) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 009-A1 | Drug | Inhaled apomorphine via Staccato aerosol, Dose 1 (low dose) each day for first 5 days, then 3 doses Dose 1 (low dose) q 2 hr on Day 6 |
|
| Measure | Description | Time Frame |
|---|---|---|
| A - Dose Proportionality of multi-dose inhaled apomorphine by Power Analysis of AUC | Dose proportionality of inhaled Staccato apomorphine AUC across all 3 doses during Days 1-5 and multiple daily dosing (all 3 doses q 2 hr per day) on Day 6 using a power model [regression of log(AUC) versus log(dose)] in subjects with established Parkinson's disease | 6 days |
| B1 - Effect on MDS-UPDRS in Parkinson's disease OFF periods | Explore in a crossover design on consecutive days the pharmacodynamics of AZ-009 compared with placebo on the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III in subjects with established Parkinson's disease experiencing regular OFF episodes. | 2 days |
| B2 - Effect on Physician Disease State Assessment in Parkinson's disease OFF periods | Explore in a crossover design on consecutive days the pharmacodynamics of AZ-009 compared with placebo on the Physician Disease State Assessment in subjects with established Parkinson's disease experiencing regular OFF episodes. | 2 days |
| B3 - Effect on Patient Assessment of ON/OFF in Parkinson's disease OFF periods | Explore in a crossover design on consecutive days the pharmacodynamics of AZ-009 compared with placebo on Patient Assessment of ON/OFF in subjects with established Parkinson's disease experiencing regular OFF episodes. | 2 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Geert J Groeneveld, MD, PhD | Center for Human Drug Research (The Netherlands) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Human Drug Research | Leiden | 2333 | Netherlands |
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| 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 |
|---|---|
| D003434 | Crossing Over, Genetic |
| ID | Term |
|---|---|
| D059765 | Homologous Recombination |
| D011995 | Recombination, Genetic |
| D055614 | Genetic Phenomena |
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This study will be conducted in subjects with established Parkinson's disease in 2 parts. Part A will examine the tolerability, safety, and pharmacokinetics of AZ-009 dose escalation ; and Part B will assess the tolerability, safety, pharmacokinetics, and pharmacodynamics of AZ-009 compared with placebo in a crossover design
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| 009-A2 | Drug | Inhaled apomorphine via Staccato aerosol, Dose 2 (middle dose) each day for first 5 days, then 3 doses Dose 2 (middle dose) q 2 hr on Day 6 |
|
| 009-A3 | Drug | Inhaled apomorphine via Staccato aerosol, Dose 3 (high dose) each day for first 5 days, then 3 doses Dose 3 (high dose) q 2 hr on Day 6 |
|
| 009-A0 | Drug | Inhaled placebo via Staccato aerosol, Dose 0 (placebo) each day for first 5 days, then 3 doses Dose 0 (placebo) q 2 hr on Day 6 |
|
| 009-B1 (active --> placebo) crossover | Drug | Up to 2 doses (Dose 3) ; minimum of 2 hrs between doses, on Day 1, followed by Up to 2 doses (placebo) ; minimum of 2 hrs between doses, on Day 2 |
|
| 009-B2 (placebo --> active) crossover | Drug | Up to 2 doses (placebo) ; minimum of 2 hrs between doses, on Day 1, followed by Up to 2 doses (Dose 3) ; minimum of 2 hrs between doses, on Day 2 |
|
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |