Outpatient Physical Therapy Intervention in Subjects With Parkinson's Disease Currently Using APOKYN®

Multicenter, outpatient trial to evaluate PT outcomes in subjects diagnosed with PD and currently using APOKYN. Those subjects who satisfy all eligibility criteria will be randomized to 2 treatment groups:

1. "APO+" (APOKYN treatment before the PT Intervention Visit) and;
2. "APO-" (APOKYN treatment withheld before the PT Intervention Visit).

The study will have:

* Baseline Assessment Visit(s) - 1 day at Investigator's clinic and PT clinic
* APOKYN Response Verification Visit - 1 day
* PT Intervention Visits - for 6 weeks
* End-of-study Assessment Visit(s) - 1 day at Investigator's clinic and PT clinic All subjects will participate in a standardized PT intervention. In both treatment groups, ALL subjects will arrive for the PT Intervention Visit in an "end-of-dose-off" motor state. The "end-of-dose-off" motor state will be achieved by the subject withholding his/her carbidopa/levodopa dose and APOKYN dose for at least 3 hours before the PT Intervention Visit. It is hypothesized that the outcome of PT will be improved when subjects are in the "on" motor state during PT Intervention visits compared with being in the "end-of-dose-off" motor state during PT Intervention visits.

• APOKYN (Drug), also known as Apomorphine, APO: Subjects in the APOKYN+ group will administer his/her usual dose of APOKYN at the PT clinic, as instructed by the Physical Therapist. These subjects will not take carbidopa/levodopa for at least 3 hours before or during the PT Intervention Visit.
• Physical Therapy (Behavioral), also known as PT: All subjects will participate in a standardized PT intervention

Primary outcomes

• Change From Baseline in Activities-specific Balance Confidence (ABC) Scale [Baseline and after week 6]: Scale from 0 to 100% where an increase in percent represents an improvement in balance confidence.

Secondary outcomes

• Change From Baseline in Movement Disorder Societies Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination) [Baseline and after week 6]: MDS-UPDRS Part III is a sub-scale of MDS-UPDRS. Sub-scale scores range from 0 (best score possible) to 72 (worst score possible). A negative change from baseline represents an improvement in motor function.
• Change From Baseline in Modified Physical Performance Test (M-PPT) [Baseline and after week 6]: Investigator scale assessing 9 domains of physical functioning where total scores range from 0 to 28 with higher scores indicating better physical performance. A positive change from baseline represents an improvement in physical performance.
• Change From Baseline in Timed-Up-and-Go (TUG) Test [Baseline and after week 6]: Test captures the amount of time for a subject to get up from an arm chair, walk 3 meters, turn around, walk back to chair, and sit. A negative change from baseline represents an improvement of physical function.
• Change From Baseline in 6-Minute Walk Test (6MWT) [Baseline and after week 6]: Objective performance based measure of functional exercise capacity that measures the distance a subject can cover on a 30 meter flat walking area over 6 minutes. A positive change from baseline represents an improvement in the distance walked (ft) in 6 minutes.
• Change From Baseline in Montreal Cognitive Assessment (MoCA) [Baseline and after week 6]: The MoCA is a validated, 30-point test (sum of the 6 domains), with scores ranging from 0 (worst) to 30 (best). The test is designed to assess several cognitive domains, including visuospatial abilities (5 points), animal naming (3 points), attention (6 points), language (3 points), abstraction (2 points), delayed recall (5 points), and orientation to time and place (6 points). Total MoCA scores higher than 26 indicate normal cognitive function. A positive change from baseline represents an improvement in cognitive function.
• Change From Baseline in MDS-UPDRS Part I A [Baseline and after week 6]: MDS-UPDRS Part I A is a sub-scale of MDS-UPDRS. Sub-scale scores range from 0 (best score possible) to 24 (worst score possible). A negative change from baseline represents an improvement in non-motor experiences of daily living (investigator rated).
• Number of Participants in Each Category of Clinical Global Impression of Change (CGI-C) [After week 6]: Investigator's impression of change in the subject's symptoms from baseline assessment visit to end of study assessment, on a 7-point scale ranging from very much improved to very much worse.
• Change From Baseline in MDS-UPDRS Part II [Baseline and after week 6]: MDS-UPDRS Part II is a sub-scale of MDS-UPDRS. Sub-scale scores range from 0 (best score possible) to 52 (worst score possible). A negative change from baseline represents an improvement in motor experience of daily living.
• Change From Baseline in MDS-UPDRS Part IV [Baseline and after week 6]: MDS-UPDRS Part IV is a sub-scale of MDS-UPDRS. Sub-scale scores range from 0 (best score possible) to 24 (worst score possible). A negative change from baseline represents fewer motor complications.
• Change From Baseline in MDS-UPDRS Part I B [Baseline and after week 6]: MDS-UPDRS Part I B is a sub-scale of MDS-UPDRS. Sub-scale scores range from 0 (best score possible) to 28 (worst score possible). A negative change from baseline represents an improvement in non-motor experiences of daily living (subject rated).
• Change From Baseline in Clinical Global Impression of Severity (CGI-S) [Baseline and after week 6]: Investigator's impression of the severity of the subject's illness on a 7-point scale ranging from normal (1) to among the most extremely ill subjects (7). A negative change from baseline represents a decrease in the severity of the subject's illness.

Other outcomes

• Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) [Baseline and after week 6]: PDQ-39 is a scale measuring subject reported aspects of functioning and well-being. Each of the 39 items is rated using a 5-points Likert scale, with 0 for never having difficulties/problems and 4 for all always having difficulties/problems. The total score is the sum of the 39 items, with a minimum score of 0 and a maximum score of 156. A negative change from baseline represents an improvement in functioning and well-being.
• Change From Baseline in Parkinson's Fatigue Scale (PFS-16) [Baseline and after week 6]: PFS-16 is a subject-reported scale evaluating the physical effects of fatigue and its impact on daily function, with a minimum score of 16 and a maximum score of 80. Ratings are based on feelings and experiences over the prior 2 weeks, with scoring ranging from 1 (strongly disagree) to 5 (strongly agree), where lower scores are associated with less fatigue and higher scores are associated with greater fatigue. A negative change from baseline represents an improvement in the physical effects of fatigue and the impact on daily function. .
• Hospital Anxiety and Depression Scale - Change From Baseline in Anxiety [Baseline and after week 6]: The Hospital Anxiety and Depression Scale is a 14-item Investigator-rated scale designed to determine levels of anxiety and depression in people with physical health problems. Seven items relate to anxiety and 7 items related to depression, where the scale ranges from 0 (best score possible) to 21 (worst score possible). A negative change from baseline represents a decrease in anxiety.
• Number of Participants in Each Category of Patient Global Impression of Change (PGI-C) [After week 6]: Self reported (caregiver, if applicable) impression of change in the subject's symptoms from baseline assessment visit to end of study assessment, on a 7-point scale ranging from much improved to very much worse.
• Change From Baseline in Number of Falls as Reported by the Subject in the Past 1 Week [Baseline and after week 6]: Subject reported number of falls. A negative change from baseline represents a decrease in the frequency of falls.
• Change From Baseline in Patient Global Impression of Severity (PGI-S) [Baseline and after week 6]: Self reported (caregiver, if applicable) impression of the severity of the subject's illness on a 7-point scale ranging from normal (1) to among the most extremely ill subjects (7). A negative change from baseline represents a decrease in the severity of the subject's illness.
• Hospital Anxiety and Depression Scale - Change From Baseline in Depression [Baseline and after week 6]: The Hospital Anxiety and Depression Scale is a 14-item Investigator-rated scale designed to determine levels of anxiety and depression in people with physical health problems. Seven items relate to anxiety and 7 items related to depression, where the scale ranges from 0 (best score possible) to 21 (worst score possible). A negative change from baseline represents a decrease in depression.

Sex: All, ages: 18 Years to 78 Years

Inclusion Criteria:

* Able to understand and sign an Investigational Review Board (IRB)-approved written informed consent and privacy language (e.g., Health Insurance Portability and Accountability Act (HIPAA) authorization) as per national regulations before any study-related procedures are performed.
* Must have a diagnosis of idiopathic PD.
* Adult male or female 18 to 78 years of age, inclusive.
* Currently using APOKYN, per the Package Insert, for at least 4 weeks before Baseline Assessment Visit(s).
* Currently using carbidopa/levodopa therapy at a steady maintenance dose, representing a stable treatment regimen in the opinion of the Investigator, for at least 4 weeks before Baseline Assessment Visit(s).
* Able to walk 50 feet independently (cane permissible) at the Baseline Assessment Visit.
* Meet all of the following parameters to demonstrate an optimal response to APOKYN at the APOKYN Response Verification Visit: must be "on" in the opinion of the subject and investigator within 20 minutes after the APOKYN injection; and have a motor state improvement of >25% per the Movement Disorder Society (MDS)-UPDRS Motor Score (Part III), within 20 minutes after the APOKYN injection, as compared to pre-injection.
* Willing and able to comply with scheduled visits, treatment plan, other study-related procedures, and have available caregiver to provide transportation to clinic visits as needed.

Exclusion Criteria:

* Received PT targeting Parkinson's disease within 6 months before Baseline Assessment Visit(s).
* Received any investigational (i.e., unapproved) drug product within the last 30 days (or 5 half-lives, whichever is longer) before the Baseline Assessment Visit(s).
* Currently taking, or likely to need to take at any time during the course of the study, any 5HT3 antagonist (i.e., ondansetron, granisetron, dolasetron, palonosetron, alosetron).
* Currently on or likely to transition to the DUOPA (carbidopa and levodopa enteral suspension) during the course of the study.
* Has orthostatic hypotension (defined as >30 mmHg decrease in systolic blood pressure or >15 mmHg decrease in diastolic blood pressure within 2 minutes of standing from a supine position) at the Baseline Assessment Visit(s), or within 20 minutes following APOKYN injection at the APOKYN Verification Visit.
* Has a score of 24 or higher on the Modified Physical Performance Test (M-PPT).
* Has a score of 80% or higher on the Activities-specific Balance Confidence Scale (ABC).
* Has any significant current medical disorder, physical, or mental condition that would, in the Investigator's opinion, represent a hazard to the subject or prevent the subject from completing the study.
* Subjects with dementia, in the Investigator's opinion, or subjects with a Montreal Cognitive Assessment (MoCA) <18.

Participant flow

Outcome results

• Change From Baseline in Activities-specific Balance Confidence (ABC) Scale (Primary), Mean, percent change: Apokyn Treatment Before Physical Therapy 3.1 +/- 8.70; Apokyn Treatment Withheld Before Physical Therapy 15.2 +/- 17.72
• Change From Baseline in Movement Disorder Societies Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination) (Secondary), Mean, units on a scale: Apokyn Treatment Before Physical Therapy -4.2 +/- 10.01; Apokyn Treatment Withheld Before Physical Therapy -0.8 +/- 7.27
• Change From Baseline in Modified Physical Performance Test (M-PPT) (Secondary), Mean, units on a scale: Apokyn Treatment Before Physical Therapy 3.8 +/- 2.93; Apokyn Treatment Withheld Before Physical Therapy 5.8 +/- 4.11
• Change From Baseline in Timed-Up-and-Go (TUG) Test (Secondary), Mean, seconds: Apokyn Treatment Before Physical Therapy -4.0 +/- 3.08; Apokyn Treatment Withheld Before Physical Therapy 0.1 +/- 2.13
• Change From Baseline in 6-Minute Walk Test (6MWT) (Secondary), Mean, feet: Apokyn Treatment Before Physical Therapy 238.7 +/- 191.88; Apokyn Treatment Withheld Before Physical Therapy 315.3 +/- 317.36
• Change From Baseline in Montreal Cognitive Assessment (MoCA) (Secondary), Mean, units on a scale: Apokyn Treatment Before Physical Therapy 0.3 +/- 1.21; Apokyn Treatment Withheld Before Physical Therapy -0.3 +/- 0.96
• Change From Baseline in MDS-UPDRS Part I A (Secondary), Mean, units on a scale: Apokyn Treatment Before Physical Therapy -0.3 +/- 1.21; Apokyn Treatment Withheld Before Physical Therapy -2.3 +/- 2.50
• Number of Participants in Each Category of Clinical Global Impression of Change (CGI-C) (Secondary), Count of participants, Participants: Apokyn Treatment Before Physical Therapy 2; Apokyn Treatment Withheld Before Physical Therapy 2
• Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) (Other pre specified), Mean, units on a scale: Apokyn Treatment Before Physical Therapy 4.8 +/- 5.71; Apokyn Treatment Withheld Before Physical Therapy -8.8 +/- 8.88
• Change From Baseline in Parkinson's Fatigue Scale (PFS-16) (Other pre specified), Mean, units on a scale: Apokyn Treatment Before Physical Therapy -3.5 +/- 10.27; Apokyn Treatment Withheld Before Physical Therapy -8.3 +/- 7.72
• Hospital Anxiety and Depression Scale - Change From Baseline in Anxiety (Other pre specified), Mean, units on a scale: Apokyn Treatment Before Physical Therapy 0.3 +/- 2.73; Apokyn Treatment Withheld Before Physical Therapy 1.0 +/- 2.83
• Number of Participants in Each Category of Patient Global Impression of Change (PGI-C) (Other pre specified), Count of participants, Participants: Apokyn Treatment Before Physical Therapy 1; Apokyn Treatment Withheld Before Physical Therapy 0
• Change From Baseline in Number of Falls as Reported by the Subject in the Past 1 Week (Other pre specified), Mean, number of falls reported: Apokyn Treatment Before Physical Therapy 0 +/- 0; Apokyn Treatment Withheld Before Physical Therapy -1.0 +/- 0.82
• Change From Baseline in MDS-UPDRS Part II (Secondary), Mean, units on a scale: Apokyn Treatment Before Physical Therapy -0.7 +/- 3.01; Apokyn Treatment Withheld Before Physical Therapy -1.3 +/- 2.87
• Change From Baseline in MDS-UPDRS Part IV (Secondary), Mean, units on a scale: Apokyn Treatment Before Physical Therapy 1.2 +/- 1.47; Apokyn Treatment Withheld Before Physical Therapy 0 +/- 1.63
• Change From Baseline in MDS-UPDRS Part I B (Secondary), Mean, units on a scale: Apokyn Treatment Before Physical Therapy 1.0 +/- 4.43; Apokyn Treatment Withheld Before Physical Therapy -0.8 +/- 3.50
• Change From Baseline in Clinical Global Impression of Severity (CGI-S) (Secondary), Mean, units on a scale: Apokyn Treatment Before Physical Therapy -0.7 +/- 0.82; Apokyn Treatment Withheld Before Physical Therapy 0 +/- 0.82
• Change From Baseline in Patient Global Impression of Severity (PGI-S) (Other pre specified), Mean, units on a scale: Apokyn Treatment Before Physical Therapy 0.4 +/- 1.14; Apokyn Treatment Withheld Before Physical Therapy 0 +/- 0.82
• Hospital Anxiety and Depression Scale - Change From Baseline in Depression (Other pre specified), Mean, units on a scale: Apokyn Treatment Before Physical Therapy -0.5 +/- 2.88; Apokyn Treatment Withheld Before Physical Therapy -1.0 +/- 2.94

Adverse events

Serious adverse events by term

Limitations and caveats: Recruitment challenges (primarily due to standardized physical therapy requirements within sites) led to trial termination. The small number of subjects resulted in statistically unreliable results.

• Mark Pirner, MD, Study director, US WorldMeds