A Study That Compares the Extent to Which Apomorphine Becomes Available in the Body After Taking Either an Investigational Drug Containing Apomorphine or Apomorphine That is Injected Under the Skin in People With PD Complicated by "OFF" Episodes

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03292016
• Collaborator: (none)
• Enrollment: 8
• Locations: 3
• Arms: 3
• Actual Duration (Months): 18.4
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A study that compares the extent to which apomorphine becomes available in the body after taking either an investigational drug containing apomorphine or apomorphine that is injected under the skin in people with PD complicated by "OFF" episodes.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Drug: APL-130277; Drug: APO-go; Drug: Apokyn	Phase 2

Detailed Description

This multi-center study will aim to evaluate the pharmacokinetics (PK) and comparative bioavailability of a single dose of APL-130277 sublingual thin film with subcutaneous (s.c.) APO-go® and s.c. APOKYN® in subjects with Parkinson's disease (PD). The dose of APOKYN® (≤ 5 mg) will be based on the subjects' current prescribed dose. The study is designed as an open-label, randomized, three-way crossover. Subjects will receive all three treatment arms with a minimum 1-day wash-out between each visit (excluding the screening visit) and will be randomly assigned to one of the six sequences

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Comparative Bioavailability Study to Evaluate the Single Dose Pharmacokinetic Properties of APL-130277 With Two Different Formulations of Subcutaneous Apomorphine in a Randomized, 3-Period Crossover Design in Subjects With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
• Actual Study Start Date: Aug 22, 2017
• Actual Primary Completion Date: Mar 5, 2019
• Actual Study Completion Date: Mar 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: APL-130277, sublingual thin film APL-130277, sublingual thin film, once daily	Drug: APL-130277; APL-130277 sublingual thin film; Other Names: amomorphine
Active Comparator: Subcutaneous APO-go Subcutaneous APO-go, once daily	Drug: APO-go; Subcutaneous APO-go; Other Names: amomorphine
Active Comparator: Subcutaneous APOKYN Subcutaneous APOKYN, once daily	Drug: Apokyn; Subcutaneous APOKYN; Other Names: amomorphine

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) [Day 1]

   Dose normalized maximum observed plasma concentration (Cmax)

2. Observed Time of the Maximum Concentration (Tmax) [Day 1]

   Time from dosing to Cmax, observed by inspection of individual subject plots of plasma concentration versus time.

3. Area Under the Concentration- Time Curve (AUC Last) [Day 1]

   area under the concentration-time curve from time zero to the last measurable plasma concentration-time curve using the linear up log down trapezoidal rule.

4. Area Under the Concentration- Time Curve (AUC Inf) [Day 1]

   area under the concentration-time curve from time zero extrapolated to infinity using the linear up log down trapezoidal rule.

5. Mean Residence Time (MRT) [Day 1]

   Mean residence time during one dosing interval calculated using the following equation: MRT = AUMCinf/AUC inf. AUMCinf is the area under the first moment (time.plasma concentration vs. time) curve.

6. Metabolite/Parent (M/P) Drug Concentration Ratio -Cmax [Day 1]

   Metabolite (apomorphine sulfate) to Parent exposure ratio, Cmax, corrected for molecular weight differences.

7. Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F) [Day 1]

   Apparent total clearance of the drug from plasma extravascular administration, calculated as Dose/AUCinf.

8. Apparent Volume of Distribution After Non-intravenous Administration (V/F) [Day 1]

   Apparent volume of distribution after extravascular administration, calculated as Dose/(AUCinf * λz).

9. Terminal-phase Half-life (t½) [Day 1]

   Terminal phase half-life, as calculated by the following equation: t½ = ln(2)/λz.

10. Terminal-phase Rate Constant ( λz) [Day 1]

    Apparent terminal elimination rate constant, determined by log linear regression of the plasma concentration versus time data that was judged to be in the log-linear elimination phase. At least 3 data points in the terminal phase will be used in the determination of the rate constant.

11. Metabolite/Parent (M/P) Drug Concentration Ratio -AUC Last [Day 1]

    Metabolite (apomorphine sulfate) to Parent exposure ratio, AUClast, corrected for molecular weight differences.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 Levodopa (L-Dopa) with well-defined "OFF" episodes, as determined by the Investigator.

4. Receiving APOKYN® of ≤ 5 mg per dose for at least 4 weeks before the Screening Visit.

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

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

7. Patients must experience a well-defined "OFF" episode in the morning if they do not take their morning PD medications on schedule, and must be willing to delay morning doses on the 3 study dosing days

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

9. Mini-Mental State Examination (MMSE) score > 23.

10. If female and of childbearing potential, must agree to use one of the following methods of birth control:

• Oral contraceptive;

• Contraceptive patch;

• Barrier (diaphragm, sponge or condom) plus spermicidal preparations;

• Intrauterine contraceptive system;

• Levonorgestrel implant;

• Medroxyprogesterone acetate contraceptive injection;

• Complete abstinence from sexual intercourse;

• Hormonal vaginal contraceptive ring; or

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

1. Male patients must be either surgically sterile, agree to be sexually abstinent or use a barrier method of birth control (e.g., condom) or maintain a monogamous relationship with a person who is not of child-bearing potential from first study drug administration until 30days after final drug administration.

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

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

Exclusion Criteria:

1. Atypical or secondary parkinsonism.

2. Previous treatment with any of the following: continuous subcutaneous (s.c.) apomorphine infusion; or Duodopa/Duopa.

3. Contraindications to APO-go® or APOKYN® or hypersensitivity to apomorphine hydrochloride or any marcrolide antibiotic or any of the ingredients APO-go® or APOKYN® (notably sodium metabisulfite).

4. Female who is pregnant or lactating.

5. Participation in a clinical trial within 30 days prior to the Screening Visit.

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

7. Any selective 5HT3 antagonists (ie, ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine and clozapine) or dopamine depleting agents within 30 days prior to the Screening Visit.

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

9. History of malignant melanoma.

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

11. 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.

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

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

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

15. Current suicidal ideation within one year prior to the Screening Visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the last 5 years.

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

17. Cankers or mouth sores within 30 days prior to the Screening Visit, 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida	United States	33486
2	Parkinson's Disese Treatment Center of SW Florida	Port Charlotte	Florida	United States	33980
3	QUEST Research Institute	Farmington Hills	Michigan	United States	48334

Sponsors and Collaborators

• Sunovion

Investigators

• Study Chair: CNS Mecdical Director, Sunovion Pharmacetuicals Inc.

Study Documents (Full-Text)

• Study Protocol - May 10, 2017
• Statistical Analysis Plan - Jan 7, 2019

More Information

Publications

None provided.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT03292016
• Other Study ID Numbers: CTH-203
• First Posted: Sep 25, 2017
• Last Update Posted: Aug 13, 2020
• Last Verified: Aug 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sunovion: Off Episodes; Parkinson Disease
• Additional relevant MeSH terms: Parkinson Disease; Apomorphine

Study Results

Participant Flow

Arm/Group Title	APL-130277, Then APOKYN, Then APO-go	APL-130277, Then APO-go, Then APOKYN	APOKYN, Then APL-130277, Then APO-go	APOKYN, Then APO-go, Then APL-130277	APO-go, Then APL-130277, Then APOKYN	APO-go, Then APOKYN, Then APL-130277
Arm/Group Description	Sequence 1: Participants first received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state. After a washout period of at least one day, they received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APO-go ( same dose as APOKYN: 2 mg/3 mg/4mg/5 mg) in the 'OFF' state.	Sequence 2: Participants first received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state. After a washout period of at least one day, they received APO-go (same dose as APOKYN 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state.	Sequence 3: Participants first received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state. After a washout period of at least one day, they received APO-go (same dose as APOKYN 2 mg/3 mg/4mg/5 mg) in the 'OFF' state.	Sequence 4: Participants first received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APO-go (same dose as APOKYN 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state.	Sequence 5: Participants first received APO-go (same dose as APOKYN 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state. After a washout period of at least one day, they received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state.	Sequence 6: Participants first received APO-go (same dose as APOKYN 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state.
Period Title: First Intervention
STARTED	1	1	2	1	1	2
COMPLETED	1	1	2	1	1	2
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention
STARTED	1	1	2	1	1	2
COMPLETED	1	1	2	1	1	2
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention
STARTED	1	1	2	1	1	2
COMPLETED	1	1	2	1	1	2
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention
STARTED	1	1	2	1	1	2
COMPLETED	1	0	2	1	1	2
NOT COMPLETED	0	1	0	0	0	0
Period Title: First Intervention
STARTED	1	0	2	1	1	2
COMPLETED	1	0	2	1	1	2
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	APL-130277, Then APOKYN, Then APO-go	APL-130277, Then APO-go, Then APOKYN	APOKYN, Then APL-130277, Then APO-go	APOKYN, Then APO-go, Then APL-130277	APO-go, Then APL-130277, Then APOKYN	APO-go, Then APOKYN, Then APL-130277	Total
Arm/Group Description	Sequence 1: Participants first received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state. After a washout period of at least one day, they received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APO-go ( same dose as APOKYN: 2 mg/3 mg/4mg/5 mg) in the 'OFF' state.	Sequence 2: Participants first received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state. After a washout period of at least one day, they received APO-go (same dose as APOKYN 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state.	Sequence 3: Participants first received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state. After a washout period of at least one day, they received APO-go (same dose as APOKYN 2 mg/3 mg/4mg/5 mg) in the 'OFF' state.	Sequence 4: Participants first received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APO-go (same dose as APOKYN 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state.	Sequence 5: Participants first received APO-go (same dose as APOKYN 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state. After a washout period of at least one day, they received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state.	Sequence 6: Participants first received APO-go (same dose as APOKYN 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APOKYN (current prescribed dose : 2 mg/3 mg/4mg/5 mg) in the 'OFF' state. After a washout period of at least one day, they received APL-130277 (approximate equivalent dose to current APOKYN dose: 15 mg/ 20 mg/ 25 mg/ 30 mg) in the 'OFF' state.	Total of all reporting groups
Overall Participants	1	1	2	1	1	2	8
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	1 100%	1 50%	0 0%	0 0%	1 50%	3 37.5%
>=65 years	1 100%	0 0%	1 50%	1 100%	1 100%	1 50%	5 62.5%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	75	51	67.5 (9.19)	67	73	68.5 (9.19)	67.3 (8.7)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 100%	0 0%	0 0%	0 0%	1 50%	2 25%
Male	1 100%	0 0%	2 100%	1 100%	1 100%	1 50%	6 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	1 100%	2 100%	1 100%	1 100%	2 100%	8 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	1 100%	1 100%	2 100%	1 100%	1 100%	2 100%	8 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Country (Count of Participants)
United States	1 100%	1 100%	2 100%	1 100%	1 100%	2 100%	8 100%
Height (cm) at Baseline (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	172.7	157.5	174.95 (11.243)	175.3	177.8	171.25 (19.445)	171.96 (10.545)
Body Weight (kg) at Baseline (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	86.3	59.4	86.7 (20.506)	73	84.4	71.2 (25.032)	77.36 (15.895)
BMI (kg/m2) at Baseline (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.9	23.9	28.1 (3.111)	23.8	26.7	23.8 (3.111)	25.89 (2.826)
ON State Mod. Hoehn & Yahr Score (Score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score]	2	2	2.5 (0)	2.5	3	2.5 (0.707)	2.44 (0.417)
Mini-Mental Status Total Score (Score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score]	30	30	26.5 (2.12)	25	27	27.5 (3.54)	27.5 (2.33)
Child-bearing potential (Count of Participants)
Yes	0 0%	1 100%	0 0%	0 0%	0 0%	0 0%	1 12.5%
No	0 0%	0 0%	0 0%	0 0%	0 0%	1 50%	1 12.5%
N/A	1 100%	0 0%	2 100%	1 100%	1 100%	1 50%	6 75%
Smoking Status (Count of Participants)
Has never smoked	1 100%	1 100%	0 0%	1 100%	1 100%	2 100%	6 75%
Former Smoker	0 0%	0 0%	2 100%	0 0%	0 0%	0 0%	2 25%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Description	Dose normalized maximum observed plasma concentration (Cmax)
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APL-130277, Sublingual Thin Film	Subcutaneous APOKYN	Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily	Subcutaneous APOKYN, once daily	Subcutaneous APO-go, once daily
Measure Participants	8	7	8
Geometric Least Squares Mean (90% Confidence Interval) [(ng/mL)/(mg)]	0.281	2.29	2.74

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APOKYN
	Comments	Sample size of 12 subjects, a two-sided 90% CI for the difference in paired PK parameter means on the log scale will have an interval that extends no more than 0.221 units from the observed difference with 90% coverage probability. Assumes CV of 35% for the difference on the original scale.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean ratio (APL-130277/APOKYN)
	Estimated Value	12.3
	Confidence Interval	(2-Sided) 90%; 7.5 to 20.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean ratio (APL-130277/APO-go)
	Estimated Value	10.3
	Confidence Interval	(2-Sided) 90%; 6.5 to 16.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous APOKYN, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments	relative bioavailibilty
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean ratio (APOKYN/APO-go)
	Estimated Value	83.4
	Confidence Interval	(2-Sided) 90%; 50.5 to 137.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.21
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 20 mg and APO-Go 3 mg

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APOKYN
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.13
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 20 mg and APOKYN 3 mg

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous APOKYN, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.16
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 3 mg and APOKYN 3 mg

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.16
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 25 mg and APO-Go 4 mg

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APOKYN
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.17
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 25 mg and APOKYN 4 mg

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous APOKYN, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.12
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 4 mg and APOKYN 4 mg

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.08
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 30 mg and APO-Go 5 mg

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APOKYN
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.09
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 30 mg and APOKYN 5 mg

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous APOKYN, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.04
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 5 mg and APOKYN 5 mg

2. Primary Outcome

Title	Observed Time of the Maximum Concentration (Tmax)
Description	Time from dosing to Cmax, observed by inspection of individual subject plots of plasma concentration versus time.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Tmax summary statistics were summarized by dose levels and the inferential statistics was done across all dose levels.

Arm/Group Title	APL-130277, Sublingual Thin Film	Subcutaneous APOKYN	Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily	Subcutaneous APOKYN, once daily	Subcutaneous APO-go, once daily
Measure Participants	8	7	8
APL 20 mg, APOKYN 3 mg, and APO-go 3 mg	0.75	0.38	0.38
APL 25 mg, APOKYN 4 mg, and APO-go 4 mg	0.63	0.25	0.26
APL 30 mg, APOKYN 5 mg, and APO-go 5 mg	0.75	0.38	0.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APOKYN
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0625
	Comments
	Method	Sign test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0313
	Comments
	Method	Sign test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous APOKYN, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.9999
	Comments
	Method	Sign test
	Comments

3. Primary Outcome

Title	Area Under the Concentration- Time Curve (AUC Last)
Description	area under the concentration-time curve from time zero to the last measurable plasma concentration-time curve using the linear up log down trapezoidal rule.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APL-130277, Sublingual Thin Film	Subcutaneous APOKYN	Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily	Subcutaneous APOKYN, once daily	Subcutaneous APO-go, once daily
Measure Participants	8	7	8
Geometric Least Squares Mean (90% Confidence Interval) [(hxng/mL)/(mg)]	0.500	2.91	3.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APOKYN
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (APL-130277/APOKYN)
	Estimated Value	17.2
	Confidence Interval	(2-Sided) 90%; 13.1 to 22.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (APL-130277/APOKYN)
	Estimated Value	16.7
	Confidence Interval	(2-Sided) 90%; 13.0 to 21.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous APOKYN, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (APOKYN/APO-go)
	Estimated Value	96.9
	Confidence Interval	(2-Sided) 90%; 74.2 to 126.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.32
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 20 mg and APO-Go 3 mg

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APOKYN
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.16
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 20 mg and APOKYN 3 mg

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous APOKYN, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.09
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 3 mg and APOKYN 3 mg

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.23
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 25 mg and APO-Go 4 mg

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APOKYN
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.23
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 25 mg and APOKYN 4 mg

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous APOKYN, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.00
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 4 mg and APOKYN 4 mg

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.15
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 30 mg and APO-Go 5 mg

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APOKYN
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.14
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APL 30 mg and APOKYN 5 mg

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous APOKYN, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.96
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The comparative bioavailability calculated as the ratio of the Test/Reference between APO-Go 5 mg and APOKYN 5 mg

4. Primary Outcome

Title	Area Under the Concentration- Time Curve (AUC Inf)
Description	area under the concentration-time curve from time zero extrapolated to infinity using the linear up log down trapezoidal rule.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APL-130277, Sublingual Thin Film	Subcutaneous APOKYN	Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily	Subcutaneous APOKYN, once daily	Subcutaneous APO-go, once daily
Measure Participants	8	7	8
Geometric Least Squares Mean (90% Confidence Interval) [(hxng/mL)/(mg)]	0.52	2.97	3.04

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APOKYN
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (APL-130277/APOKYN)
	Estimated Value	17.6
	Confidence Interval	(2-Sided) 90%; 13.7 to 22.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (APL-130277/APO-go)
	Estimated Value	17.2
	Confidence Interval	(2-Sided) 90%; 13.7 to 21.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous APOKYN, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (APOKYN/APO-go)
	Estimated Value	97.8
	Confidence Interval	(2-Sided) 90%; 76.6 to 124.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Mean Residence Time (MRT)
Description	Mean residence time during one dosing interval calculated using the following equation: MRT = AUMCinf/AUC inf. AUMCinf is the area under the first moment (time.plasma concentration vs. time) curve.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

MRT was summarized by dose level

Arm/Group Title	APL-130277, Sublingual Thin Film	Subcutaneous APOKYN	Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily	Subcutaneous APOKYN, once daily	Subcutaneous APO-go, once daily
Measure Participants	8	6	7
APL 20 mg, APOKYN 3 mg, and APO-go 3 mg	1.69 (5.2)	1.44 (4.3)	1.21 (19.3)
APL 25 mg, APOKYN 4 mg, and APO-go 4 mg	1.83 (41.5)	1.70 (13.8)	1.51 (19.0)
APL 30 mg, APOKYN 5 mg, and APO-go 5 mg	2.15 (15.9)	1.23 (3.4)	1.08 (35.4)

6. Primary Outcome

Title	Metabolite/Parent (M/P) Drug Concentration Ratio -Cmax
Description	Metabolite (apomorphine sulfate) to Parent exposure ratio, Cmax, corrected for molecular weight differences.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Metabolite/Parent Cmax summarized by dose level

Arm/Group Title	APL-130277, Sublingual Thin Film	Subcutaneous APOKYN	Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily	Subcutaneous APOKYN, once daily	Subcutaneous APO-go, once daily
Measure Participants	8	6	7
APL 20 mg, APOKYN 3 mg and APO-go 3 mg	61.6 (28.8)	15.2 (48.9)	11.5 (4.0)
APL 25 mg, APOKYN 4 mg and APO-go 4 mg	32.0 (157.1)	9.0 (149.3)	7.1 (240.3)
APL 30 mg, APOKYN 5 mg and APO-go 5 mg	61.2 (87.0)	13.7 (8.2)	11.3 (47.6)

7. Primary Outcome

Title	Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F)
Description	Apparent total clearance of the drug from plasma extravascular administration, calculated as Dose/AUCinf.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

CL/F summarized by dose level

Arm/Group Title	APL-130277, Sublingual Thin Film	Subcutaneous APOKYN	Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily	Subcutaneous APOKYN, once daily	Subcutaneous APO-go, once daily
Measure Participants	8	6	7
APL 20 mg, APOKYN 3 mg and APO-go 3 mg	2766.9 (52.4)	407.9 (33.3)	375.6 (32.2)
APL 25 mg, APOKYN 4 mg and APO-go 4 mg	1097.8 (99.5)	250.2 (140.6)	253.7 (169.6)
APL 30 mg, APOKYN 5 mg and APO-go 5 mg	1952.1 (44.3)	350.6 (4.0)	299.2 (41.0)

8. Primary Outcome

Title	Apparent Volume of Distribution After Non-intravenous Administration (V/F)
Description	Apparent volume of distribution after extravascular administration, calculated as Dose/(AUCinf * λz).
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

V/F summarized by dose level

Arm/Group Title	APL-130277, Sublingual Thin Film	Subcutaneous APOKYN	Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily	Subcutaneous APOKYN, once daily	Subcutaneous APO-go, once daily
Measure Participants	8	8	7
APL 20 mg, APOKYN 3 mg and APO-go 3 mg	4440.2 (72.0)	577.5 (44.3)	469.3 (19.1)
APL 25 mg, APOKYN 4 mg and APO-go 4 mg	1733.4 (52.8)	420.8 (193.7)	372.2 (231.1)
APL 30 mg, APOKYN 5 mg and APO-go 5 mg	3419.5 (67.4)	452.0 (14.7)	324.2 (73.7)

9. Primary Outcome

Title	Terminal-phase Half-life (t½)
Description	Terminal phase half-life, as calculated by the following equation: t½ = ln(2)/λz.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Terminal-phase half-life summarized by dose level

Arm/Group Title	APL-130277, Sublingual Thin Film	Subcutaneous APOKYN	Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily	Subcutaneous APOKYN, once daily	Subcutaneous APO-go, once daily
Measure Participants	8	8	7
APL 20 mg, APOKYN 3 mg and APO-go 3 mg	1.11 (15.6)	0.98 (9.9)	0.87 (12.6)
APL 25 mg, APOKYN 4 mg and APO-go 4 mg	1.09 (34.3)	1.17 (20.6)	1.02 (19.7)
APL 30 mg, APOKYN 5 mg and APO-go 5 mg	1.21 (20.5)	0.89 (18.7)	0.75 (35.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0313
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	APL-130277, Sublingual Thin Film, Subcutaneous APOKYN
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0625
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Subcutaneous APOKYN, Subcutaneous APO-go
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.9999
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Primary Outcome

Title	Terminal-phase Rate Constant ( λz)
Description	Apparent terminal elimination rate constant, determined by log linear regression of the plasma concentration versus time data that was judged to be in the log-linear elimination phase. At least 3 data points in the terminal phase will be used in the determination of the rate constant.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

terminal-phase rate constant summarized by dose level

Arm/Group Title	APL-130277, Sublingual Thin Film	Subcutaneous APOKYN	Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily	Subcutaneous APOKYN, once daily	Subcutaneous APO-go, once daily
Measure Participants	8	6	7
APL 20 mg, APOKYN 3 mg and APO-go 3 mg	0.62 (15.6)	0.71 (9.9)	0.80 (12.6)
APL 25 mg, APOKYN 4 mg and APO-go 4 mg	0.63 (34.3)	0.59 (20.6)	0.68 (19.7)
APL 30 mg, APOKYN 5 mg and APO-go 5 mg	0.57 (20.5)	0.78 (18.7)	0.92 (35.5)

11. Primary Outcome

Title	Metabolite/Parent (M/P) Drug Concentration Ratio -AUC Last
Description	Metabolite (apomorphine sulfate) to Parent exposure ratio, AUClast, corrected for molecular weight differences.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Metabolite/Parent (M/P) drug concentration Ratio -AUC last summarized by dose level

Arm/Group Title	APL-130277, Sublingual Thin Film	Subcutaneous APOKYN	Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily	Subcutaneous APOKYN, once daily	Subcutaneous APO-go, once daily
Measure Participants	8	8	7
APL 20 mg, APOKYN 3 mg and APO-go 3 mg	98.16 (6.4)	36.22 (3.0)	32.19 (9.9)
APL 25 mg, APOKYN 4 mg and APO-go 4 mg	45.79 (169.9)	18.70 (162.8)	16.27 (221.6)
APL 30 mg, APOKYN 5 mg and APO-go 5 mg	98.07 (55.4)	33.63 (6.2)	26.22 (43.6)

Adverse Events

Time Frame	16 days
Arm/Group Title	APL-130277, Sublingual Thin Film		Subcutaneous APOKYN		Subcutaneous APO-go
Arm/Group Description	APL-130277, sublingual thin film, once daily		Subcutaneous APOKYN, once daily		Subcutaneous APO-go, once daily
All Cause Mortality
	APL-130277, Sublingual Thin Film		Subcutaneous APOKYN		Subcutaneous APO-go
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/7 (0%)		0/8 (0%)
Serious Adverse Events
	APL-130277, Sublingual Thin Film		Subcutaneous APOKYN		Subcutaneous APO-go
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		0/7 (0%)		0/8 (0%)
Injury, poisoning and procedural complications
Fall	1/8 (12.5%)	1	0/7 (0%)	0	0/8 (0%)	0
Rib fracture	1/8 (12.5%)	1	0/7 (0%)	0	0/8 (0%)	0
Splenic rupture	1/8 (12.5%)	1	0/7 (0%)	0	0/8 (0%)	0
Other (Not Including Serious) Adverse Events
	APL-130277, Sublingual Thin Film		Subcutaneous APOKYN		Subcutaneous APO-go
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		1/7 (14.3%)		3/8 (37.5%)
Gastrointestinal disorders
Nausea	1/8 (12.5%)	1	1/7 (14.3%)	1	2/8 (25%)	2
General disorders
Injection site bruising	0/8 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Nervous system disorders
Dyskinesia	0/8 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1
Somnolence	0/8 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/8 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish.