Open-Label Phase 3 Study to Examine the Long-Term Safety, Tolerability and Efficacy of APL-130277 for the Acute Treatment of "OFF" Episodes in Patients With Parkinson's Disease

Parkinson Disease Clinical Trial

Official title:

An Open-Label, Phase 3 Study Examining the Long-Term Safety, Tolerability and Efficacy of APL-130277 in Levodopa Responsive Patients With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02542696
• Other study ID #: CTH-301
• Secondary ID: 2016-000637-43
• Status: Completed
• Phase: Phase 3
• Start date: August 31, 2015
• Est. completion date: November 8, 2022

Study information

• Verified date: October 2023
• Source: Sumitomo Pharma America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An Open-Label Phase 3 Study to Examine the Long-Term Safety, Tolerability and Efficacy of APL-130277 for the Acute Treatment of "OFF" Episodes in Patients With Parkinson's Disease

Recruitment information / eligibility

• Status: Completed
• Enrollment: 496
• Est. completion date: November 8, 2022
• Est. primary completion date: November 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

De Novo Subjects Inclusion Criteria

1. Male or female = 18 years of age.

2. Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion)

3. Clinically meaningful response to L-Dopa as determined by the Investigator.

4. Receiving stable doses of L-Dopa/carbidopa (immediate or CR) administered at least 4 times per day OR Rytary™ administered at least 3 times per day, for at least 4 weeks before the initial Screening Visit (SV1). Adjunctive PD medication regimens must be maintained at a stable dose for at least 4 weeks prior to the initial Screening Visit (SV1) with the exception that MAO-B inhibitors must be maintained at a stable level for at least 8 weeks prior to the initial Screening Visit (SV1).

5. No planned medication change(s) or surgical intervention anticipated during the course of study.

6. Subject must experience at least one well defined "OFF" episode per day with a total daily "OFF" time duration of = 2 hours during the waking day, based on patient self-assessment.

7. Subject and/or caregiver must be trained in performing home dosing diary assessments of the motor state and must be able to recognize "ON" and "OFF" states.

8. Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.

9. MMSE score > 25.

10. If female and of childbearing potential, must agree to be sexually abstinent or use one of the following highly effective methods of birth control:

• Hormonal contraceptives (eg, combined oral contraceptives, patch, vaginal ring, injectables, and implants);

• Intrauterine contraceptive system;

• Surgical sterilization or partner sterile (must have documented proof); AND

One of the following effective methods of birth control:

• Male/female condom;

• Cervical cap with spermicide;

• Diaphragm with spermicide;

• Contraceptive sponge.

11. Male subjects must be either surgically sterile, agree to be sexually inactive or use a double-barrier method of birth control (eg, condom and diaphragm with spermicide, condom with cervical cap and spermicide) from first study drug administration until 90 days after final drug administration.

12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.

13. Able to understand the consent form, and to provide written informed consent.

De Novo Subjects Exclusion Criteria -

1. Atypical or secondary parkinsonism.

2. Previous treatment with any of the following: a neurosurgical procedure for PD; continuous s.c. apomorphine infusion; Duodopa/Duopa; or APL-130277.

3. Treatment with any form of s.c. apomorphine within 7 days prior to the second Screening Visit (SV2). Patients that stopped s.c. apomorphine for any reason other than systemic safety concerns or lack of efficacy may be considered.

4. Contraindications to APOKYN®, or hypersensitivity to apomorphine hydrochloride or any of the ingredients of APOKYN® (notably sodium metabisulfite).

5. Female who is pregnant or lactating.

6. Participation in a clinical trial within 30 days prior to the initial Screening Visit (SV1).

7. Receipt of any investigational (ie, unapproved) medication within 30 days prior to the initial Screening Visit (SV1).

8. Currently taking selective 5HT3 antagonists (ie, ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine or clozapine) or dopamine depleting agents.

9. Drug or alcohol dependency in the past 12 months.

10. Subject has a history of malignancy within 5 years prior to the Screening visit, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Pituitary tumors of any duration are excluded.

11. Clinically significant medical, surgical, or laboratory abnormality in the opinion of the Investigator.

12. Major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis, or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.

13. History of clinically significant hallucinations during the past 6 months.

14. History of clinically significant impulse control disorder(s).

15. Dementia that precludes providing informed consent or would interfere with participation in the study.

16. Current suicidal ideation within one year prior to the second Screening Visit (SV2) as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the C-SSRS or attempted suicide within the last 5 years.

17. Donation of blood or plasma in the 30 days prior to first dosing.

18. Presence of canker or mouth sores in the 30 days prior to the initial Screening Visit (SV1), or other clinically significant oral pathology in the opinion of the Investigator. The Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling a patient into the study.

Rollover Subjects Inclusion Criteria

1. Completion of any of the following studies: CTH-201, CTH-203, CTH-300, or CTH 302; and, in the opinion of the Investigator, would benefit from continued treatment with APL 130277.

2. No major changes in concomitant PD medications since completion of any of the following studies: CTH-201, CTH-203, CTH-300, or CTH 302. Any change in PD medications since the previous study should be discussed with the Medical Monitor to determine subject eligibility in the current study.

3. If female and of childbearing potential, must agree to be sexually abstinent or use one of the following highly effective methods of birth control:

• Hormonal contraceptives (eg, combined oral contraceptives, patch, vaginal ring, injectables, and implants);

• Intrauterine contraceptive system;

• Surgical sterilization or partner sterile (must have documented proof); AND

One of the following effective methods of birth control:

• Male/female condom;

• Cervical cap with spermicide;

• Diaphragm with spermicide;

• Contraceptive sponge.

4. Male subjects must be either surgically sterile, agree to be sexually inactive or use a double-barrier method of birth control (eg, condom and diaphragm with spermicide, condom with cervical cap and spermicide) from first study drug administration until 90 days after final drug administration.

5. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.

6. Able to understand the consent form, and to provide written informed consent.

Rollover Subjects Exclusion Criteria

1. Female who is pregnant or lactating.

2. Presence of any major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis (including clinically significant hallucinations during the past 6 months) or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.

3. Presence of any clinically significant medical (including but not limited to CNS, cardiovascular, hepatic, pulmonary, metabolic, or renal events), surgical, or laboratory abnormality that would make study participation unsafe or make treatment compliance difficult. Clinical significance to be determined by the Investigator.

4. Receipt of any investigational (ie, unapproved) medication or participation in any clinical trial of an investigational product since completing a previous study using APL 130277.

5. Development of canker or mouth sores within 14 days of completing a previous study using APL-130277. For other clinically significant oral pathology, the Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling such a subject into the study. Clinical significance to be determined by the Investigator. The eligibility of subjects who have experienced AEs related to the oral cavity during the previous study using APL-130277, should be reviewed with the medical monitor and approval obtained.

6. Current suicidal ideation within one year of the screening visit, as evidenced by answering "yes" to Question 4 or 5 on the suicidal ideation portion of the C SSRS at Screening or attempted suicide within 5 years.

CTH-301 Completer Subjects Inclusion Criteria

1. Completion of the CTH-301 study under protocol version 3.00, and in the opinion of the Investigator, would benefit from continued treatment with APL 130277.

2. If female and of childbearing potential, must agree to be sexually abstinent or use one of the following highly effective methods of birth control:

• Hormonal contraceptives (eg, combined oral contraceptives, patch, vaginal ring, injectables, and implants);

• Intrauterine contraceptive system;

• Surgical sterilization or partner sterile (must have documented proof); AND

One of the following effective methods of birth control:

• Male/female condom;

• Cervical cap with spermicide;

• Diaphragm with spermicide;

• Contraceptive sponge.

3. Male subjects must be either surgically sterile, agree to be sexually inactive or use a double-barrier method of birth control (eg, condom and diaphragm with spermicide, condom with cervical cap and spermicide) from first study drug administration until 90 days after final drug administration.

4. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.

5. Able to understand the consent form, and to provide written informed consent.

CTH-301 Completer Subjects Exclusion Criteria

1. Female who is pregnant or lactating.

2. Presence of any major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis (including clinically significant hallucinations during the past 6 months) or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation in unsafe or make treatment compliance difficult.

3. Presence of any clinically significant medical (including but not limited to CNS, cardiovascular, hepatic, pulmonary, metabolic, or renal events), surgical, or laboratory abnormality that would make study participation unsafe or make treatment compliance difficult. Clinical significance to be determined by the Investigator.

4. Receipt of any investigational (ie, unapproved) medication or participation in any clinical trial since completing the CTH 301 study.

5. Development of canker or mouth sores since completing the CTH 301 study. For other clinically significant oral pathology, the Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling such a patient into the study. Clinical significance to be determined by the Investigator.

6. Current suicidal ideation as evidenced by answering "yes" to Question 4 or 5 on the suicidal ideation portion of the C-SSRS at the Screening Visit Phase 2 (SVP2).

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• APL-130277
Used to treat up to 5 "OFF" episodes per day

Locations

Country	Name	City	State
Austria	Medical University Innsbruck Neurology Department	Innsbruck
Austria	Wilhelminenspital Department of Neurology	Wien
Canada	UHN Toronto Western Hospital	Toronto	Ontario
France	Centre d'Investigation Clinique, CIC 1436, CHU Purpan	Toulouse
Germany	St. Josef-Hospital, Klinikum der Ruhr-Universitaet-Bochum, Neurologische Klinik	Bochum
Germany	Universitätsklinikum Ulm Neurologisches Studienzentrum im RKU	Ulm
Italy	Ospedali Riuniti di Ancona	Ancona
Italy	Centro Ricerche San Raffaele	Cassino
Italy	Aging Research Center, Ce.S.I. University Foundation, Chieti-Pescara Behavioural Neurology & Movement Disorders Unit	Chieti
Italy	IRCCS San Raffaele Pisana - Clinical Trial Center	Rome
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari General de Catalunya	Sant Cugat del Vallés
United Kingdom	Fairfield General Hospital	Bury
United Kingdom	Royal Devon & Exeter NHS Foundation Trust	Exeter
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Forth Valley Royal Hospital	Larbert	Stirlingshire
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	Imperial College Healthcare Trust NHS	London
United Kingdom	Kings College, The Maurice Wohl Neuroscience Institute	London	Greater London
United Kingdom	Newcastle University	Newcastle-upon-Tyne	Northumberland
United Kingdom	Plymouth University	Plymouth
United Kingdom	Manchester University	Salford	Greater Manchester
United States	Emory University Department of Neurology	Atlanta	Georgia
United States	GRU Movement Disorders	Augusta	Georgia
United States	University of Colorado School of Medicine	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Parkinsons Disease and Movement Disorders Center	Boca Raton	Florida
United States	SUNY Downstate Medical Center, Department of Neurology	Brooklyn	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Adult Neurology	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Duke University - Movement Disorders Clinic	Durham	North Carolina
United States	Michigan State University - Dept. of Neurology	East Lansing	Michigan
United States	QUEST Research Institute	Farmington Hills	Michigan
United States	The Parkinson's and Movement Disorder Institute	Fountain Valley	California
United States	NorthShore Neurological Institute B043D	Glenview	Illinois
United States	Park Nicolet Institute - Stuthers Parkinson's Center	Golden Valley	Minnesota
United States	Houston Methodist Neurological Institute	Houston	Texas
United States	University of Iowa Dept. of Neurology	Iowa City	Iowa
United States	UC Irvine Health Gottschalk Medical Plaza	Irvine	California
United States	Kansas University Medical Center-Department of Neurology	Kansas City	Kansas
United States	Evergreen Health	Kirkland	Washington
United States	University of Kentucky	Lexington	Kentucky
United States	Clinical Trials, Inc.	Little Rock	Arkansas
United States	Keck Medical Center at USC	Los Angeles	California
United States	University of Miami, Miller School of Medicine	Miami	Florida
United States	Bendheim Parkinson's and Movement Disorder Center (Mount Sinai Medical Center)	New York	New York
United States	Columbia University Medical Center - Neurological Institute, Movement Disorders	New York	New York
United States	Jefferson University Hospital Philadelphia	Philadelphia	Pennsylvania
United States	Muhammed Ali Parkinson and Movement Disorder Center/Barrow Neurological Institute	Phoenix	Arizona
United States	Parkinson's Disease Treatment Center of Southwest Florida	Port Charlotte	Florida
United States	Raleigh Neurology Associates, P.A.	Raleigh	North Carolina
United States	Suncoast Neuroscience Associates Inc.	Saint Petersburg	Florida
United States	Movement Disorders Center of Arizona	Scottsdale	Arizona
United States	Swedish Neuroscience Research	Seattle	Washington
United States	USF Parkinson's Disease and Movement Disorder Center	Tampa	Florida
United States	UT Gardner-McMaster Parkinson's Center	Toledo	Ohio
United States	The Movement Disorder Clinic of Oklahoma	Tulsa	Oklahoma
United States	East Texas Medical Center	Tyler	Texas
United States	Sentara Neuroscience Institute	Virginia Beach	Virginia
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Henry Ford Hospital	West Bloomfield	Michigan
United States	Central DuPage Hospital - Neurodegenerative Clinic - Movement Disorders Center	Winfield	Illinois
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sumitomo Pharma America, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Canada,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of Safety and Tolerability Data Collected, Based on Number of Participants With Adverse Events in the LTS Phase	Number of Participants (%) with Adverse Events in the LTS Phase	up to approximately 3 years
Secondary	The Percentage of Instances Where a Full "ON" Response Was Achieved Within 30 Minutes After Self-administration of Study Medication at Week 24 Visit (LTS V4) of the LTS Phase Based on the Home Dosing Diary Entries.	The percentage of instances where a full "ON" response was achieved	Week 24
Secondary	The Percentage of Instances Where a Full "ON" Response Was Achieved Within 30 Minutes After Self-administration of Study Medication at Week 36 Visit (LTS V5) of the LTS Phase Based on the Home Dosing Diary Entries.		Week 36
Secondary	The Percentage of Instances Where a Full "ON" Response Was Achieved Within 30 Minutes After Self-administration of Study Medication at Week 48 Visit (LTS V6) of the LTS Phase Based on the Home Dosing Diary Entries.		Week 48
Secondary	Percentage of Subjects With a Subject-rated Full "ON" Response Within 30 Minutes at Week 24 Visit (LTS V4) of the LTS Phase.		Week 24
Secondary	Percentage of Subjects With a Subject-rated Full "ON" Response Within 30 Minutes at Week 36 Visit (LTS V5) of the LTS Phase.		Week 36
Secondary	Percentage of Subjects With a Subject-rated Full "ON" Response Within 30 Minutes at Week 48 Visit (LTS V6) of the LTS Phase.		Week 48
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 15 Minutes After Dosing at Week 24 Visit (LTS V4) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 24, 15 mins after dosing
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 30 Minutes After Dosing at Week 24 Visit (LTS V4) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 24, 30 mins after dosing
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 60 Minutes After Dosing at Week 24 Visit (LTS V4) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 24, 60 mins after dosing
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 90 Minutes After Dosing at Week 24 Visit (LTS V4) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 24, 90 mins after dosing
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 15 Minutes After Dosing at Week 36 Visit (LTS V5) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 36, 15 mins after dosing
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 30 Minutes After Dosing at Week 36 Visit (LTS V5) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 36, 30 mins after dosing
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 60 Minutes After Dosing at Week 36 Visit (LTS V5) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 36, 60 mins after dosing
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 90 Minutes After Dosing at Week 36 Visit (LTS V5) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 36, 90 mins after dosing
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 15 Minutes After Dosing at Week 48 Visit (LTS V6) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 48, 15 mins after dosing
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 30 Minutes After Dosing at Week 48 Visit (LTS V6) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 48, 30 mins after dosing
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 60 Minutes After Dosing at Week 48 Visit (LTS V6) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 48, 60 mins after dosing
Secondary	Mean Change From Pre-dose in MDS-UPDRS Part III Motor Examination (MDS UPDRS MOTOR) Score at 90 Minutes After Dosing at Week 48 Visit (LTS V6) of the LTS Phase.	The summary score used here is Part III motor examination score. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4 (0=normal, 1=slight, 2=mild, 3= moderate, and 4=severe). The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).	Week 48, 90 mins after dosing