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

Phase 4

Terminated

Conditions: Parkinson's Disease
Motor Symptoms

Interventions: Drug: APOKYN
Behavioral: Physical Therapy

Registration Number: NCT02549573

Lead Sponsor: MDD US Operations, LLC a subsidiary of Supernus Pharmaceuticals

Brief Summary: To determine if PT intervention will be improved while in the "on" motor state vs. the "end-of-dose-off" motor state during the PT Intervention Visit in subjects with PD.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 13

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Apokyn treatment before physical therapy	Physical Therapy	APOKYN treatment before the PT Intervention Visit. Subjects in the "APO+" group will administer their 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.
Apokyn treatment withheld before physical therapy	Physical Therapy	APOKYN treatment withheld before the PT Intervention Visit. Subjects in the "APO-" group will not take carbidopa/levodopa and APOKYN for at least 3 hours before or during the PT Intervention Visit. No "rescue therapy" will be allowed during the PT. Intervention Visit. If the PT Intervention Visit needs to be stopped early, the Physical Therapist will record this along with a reason for the discontinuation.
Apokyn treatment before physical therapy	APOKYN	APOKYN treatment before the PT Intervention Visit. Subjects in the "APO+" group will administer their 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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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 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 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 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.