Trial Outcomes & Findings for A Study of an Investigational Drug to See How it Affects the People With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes) Compared to an Approved Drug Used to Treat People With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes) (NCT NCT03391882)
NCT ID: NCT03391882
Last Updated: 2022-12-16
Results Overview
The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society. The summary score used in this study for the primary objective and primary efficacy endpoint is Part III motor examination score. Each Part III item has a 0-4 rating, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. 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. 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).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
113 participants
Primary outcome timeframe
Pre-dose to 90 minutes post-dose at Week 4 of each treatment period (Visit 3 and 6)
Results posted on
2022-12-16
Participant Flow
Participant milestones
| Measure |
APL-SC
Part A - Titration Phase: APL (APL-130277) then SC (subcutaneous apomorphine); Did not continue in Part B - Treatment Phase.
|
SC-APL
Part A - Titration Phase: SC (subcutaneous apomorphine) then apomorphine hydrochloride APL (APL-130277); Did not continue in Part B - Treatment Phase.
|
APL-SC-APL-SC
Part A - Titration Phase: APL (APL-130277) then SC (subcutaneous apomorphine) into Part B - Treatment Phase: APL then SC
|
APL-SC-SC-APL
Part A - Titration Phase: APL (APL-130277) then SC (subcutaneous apomorphine); Randomized into Part B - Treatment Phase: SC then APL
|
SC-APL-APL-SC
Part A - Titration Phase: SC (subcutaneous apomorphine) then APL (APL-130277); Randomized into Part B - Treatment Phase: APL then SC
|
SC-APL-SC-APL
Part A - Titration Phase: SC (subcutaneous apomorphine) then APL (APL-130277); Randomized into Part B - Treatment Phase: SC then APL
|
|---|---|---|---|---|---|---|
|
Study Overall
STARTED
|
20
|
19
|
19
|
18
|
18
|
19
|
|
Study Overall
Safety Population
|
20
|
18
|
19
|
18
|
18
|
19
|
|
Study Overall
Modified Intent-to-Treat Population
|
20
|
18
|
19
|
18
|
18
|
19
|
|
Study Overall
COMPLETED
|
0
|
0
|
16
|
15
|
14
|
15
|
|
Study Overall
NOT COMPLETED
|
20
|
19
|
3
|
3
|
4
|
4
|
|
Part A - Titration Phase
STARTED
|
20
|
19
|
19
|
18
|
18
|
19
|
|
Part A - Titration Phase
Safety Population Part A
|
20
|
18
|
19
|
18
|
18
|
19
|
|
Part A - Titration Phase
Modified Intent-to-Treat Population Part A
|
20
|
18
|
19
|
18
|
18
|
19
|
|
Part A - Titration Phase
COMPLETED
|
2
|
3
|
19
|
18
|
18
|
19
|
|
Part A - Titration Phase
NOT COMPLETED
|
18
|
16
|
0
|
0
|
0
|
0
|
|
Post Part A / Pre Part B
STARTED
|
2
|
3
|
19
|
18
|
18
|
19
|
|
Post Part A / Pre Part B
COMPLETED
|
0
|
0
|
19
|
18
|
18
|
19
|
|
Post Part A / Pre Part B
NOT COMPLETED
|
2
|
3
|
0
|
0
|
0
|
0
|
|
Part B - Treatment Phase
STARTED
|
0
|
0
|
19
|
18
|
18
|
19
|
|
Part B - Treatment Phase
Safety Population Part B
|
0
|
0
|
19
|
18
|
18
|
19
|
|
Part B - Treatment Phase
Modified Intent-to-Treat Population Part B
|
0
|
0
|
19
|
18
|
18
|
19
|
|
Part B - Treatment Phase
COMPLETED
|
0
|
0
|
16
|
15
|
14
|
15
|
|
Part B - Treatment Phase
NOT COMPLETED
|
0
|
0
|
3
|
3
|
4
|
4
|
Reasons for withdrawal
| Measure |
APL-SC
Part A - Titration Phase: APL (APL-130277) then SC (subcutaneous apomorphine); Did not continue in Part B - Treatment Phase.
|
SC-APL
Part A - Titration Phase: SC (subcutaneous apomorphine) then apomorphine hydrochloride APL (APL-130277); Did not continue in Part B - Treatment Phase.
|
APL-SC-APL-SC
Part A - Titration Phase: APL (APL-130277) then SC (subcutaneous apomorphine) into Part B - Treatment Phase: APL then SC
|
APL-SC-SC-APL
Part A - Titration Phase: APL (APL-130277) then SC (subcutaneous apomorphine); Randomized into Part B - Treatment Phase: SC then APL
|
SC-APL-APL-SC
Part A - Titration Phase: SC (subcutaneous apomorphine) then APL (APL-130277); Randomized into Part B - Treatment Phase: APL then SC
|
SC-APL-SC-APL
Part A - Titration Phase: SC (subcutaneous apomorphine) then APL (APL-130277); Randomized into Part B - Treatment Phase: SC then APL
|
|---|---|---|---|---|---|---|
|
Study Overall
Adverse Event
|
3
|
6
|
1
|
1
|
3
|
1
|
|
Study Overall
Lack of Efficacy
|
13
|
9
|
0
|
0
|
0
|
0
|
|
Study Overall
Withdrawal by Subject
|
3
|
3
|
2
|
2
|
1
|
3
|
|
Study Overall
EARLY TERM AT SPONSOR REQUEST
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Study Overall
Protocol Violation
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Part A - Titration Phase
Adverse Event
|
3
|
6
|
0
|
0
|
0
|
0
|
|
Part A - Titration Phase
Lack of Efficacy
|
12
|
6
|
0
|
0
|
0
|
0
|
|
Part A - Titration Phase
Withdrawal by Subject
|
3
|
3
|
0
|
0
|
0
|
0
|
|
Part A - Titration Phase
EARLY TERM AT SPONSOR REQUEST
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Post Part A / Pre Part B
Lack of Efficacy
|
1
|
3
|
0
|
0
|
0
|
0
|
|
Post Part A / Pre Part B
Protocol Violation
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Part B - Treatment Phase
Adverse Event
|
0
|
0
|
1
|
1
|
3
|
1
|
|
Part B - Treatment Phase
Withdrawal by Subject
|
0
|
0
|
2
|
2
|
1
|
3
|
Baseline Characteristics
safety population
Baseline characteristics by cohort
| Measure |
APL-SC
n=20 Participants
Part A - Titration Phase: APL (APL-130277) then SC (subcutaneous apomorphine); Did not continue in Part B - Treatment Phase.
|
SC-APL
n=18 Participants
Part A - Titration Phase: SC (subcutaneous apomorphine) then apomorphine hydrochloride APL (APL-130277); Did not continue in Part B - Treatment Phase.
|
APL-SC-APL-SC
n=19 Participants
Part A - Titration Phase: APL (APL-130277) then SC (subcutaneous apomorphine) into Part B - Treatment Phase: APL then SC
|
APL-SC-SC-APL
n=18 Participants
Part A - Titration Phase: APL (APL-130277) then SC (subcutaneous apomorphine); Randomized into Part B - Treatment Phase: SC then APL
|
SC-APL-APL-SC
n=18 Participants
Part A - Titration Phase: SC (subcutaneous apomorphine) then APL (APL-130277); Randomized into Part B - Treatment Phase: APL then SC
|
SC-APL-SC-APL
n=19 Participants
Part A - Titration Phase: SC (subcutaneous apomorphine) then APL (APL-130277); Randomized into Part B - Treatment Phase: SC then APL
|
Total
n=112 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=20 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=112 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=20 Participants
|
8 Participants
n=18 Participants
|
8 Participants
n=19 Participants
|
10 Participants
n=18 Participants
|
9 Participants
n=18 Participants
|
8 Participants
n=19 Participants
|
52 Participants
n=112 Participants
|
|
Age, Categorical
>=65 years
|
11 Participants
n=20 Participants
|
10 Participants
n=18 Participants
|
11 Participants
n=19 Participants
|
8 Participants
n=18 Participants
|
9 Participants
n=18 Participants
|
11 Participants
n=19 Participants
|
60 Participants
n=112 Participants
|
|
Age, Continuous
|
64.9 Years
STANDARD_DEVIATION 8.33 • n=20 Participants
|
63.9 Years
STANDARD_DEVIATION 9.99 • n=18 Participants
|
65.0 Years
STANDARD_DEVIATION 9.80 • n=19 Participants
|
63.2 Years
STANDARD_DEVIATION 6.91 • n=18 Participants
|
63.4 Years
STANDARD_DEVIATION 9.71 • n=18 Participants
|
65.6 Years
STANDARD_DEVIATION 8.69 • n=19 Participants
|
64.4 Years
STANDARD_DEVIATION 8.80 • n=112 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=20 Participants
|
7 Participants
n=18 Participants
|
6 Participants
n=19 Participants
|
1 Participants
n=18 Participants
|
6 Participants
n=18 Participants
|
7 Participants
n=19 Participants
|
34 Participants
n=112 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=20 Participants
|
11 Participants
n=18 Participants
|
13 Participants
n=19 Participants
|
17 Participants
n=18 Participants
|
12 Participants
n=18 Participants
|
12 Participants
n=19 Participants
|
78 Participants
n=112 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=20 Participants
|
3 Participants
n=18 Participants
|
1 Participants
n=19 Participants
|
1 Participants
n=18 Participants
|
2 Participants
n=18 Participants
|
1 Participants
n=19 Participants
|
8 Participants
n=112 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=20 Participants
|
15 Participants
n=18 Participants
|
18 Participants
n=19 Participants
|
16 Participants
n=18 Participants
|
16 Participants
n=18 Participants
|
18 Participants
n=19 Participants
|
102 Participants
n=112 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=20 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
1 Participants
n=18 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
2 Participants
n=112 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=20 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=112 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=20 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=112 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=20 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=112 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=20 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=112 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=20 Participants
|
18 Participants
n=18 Participants
|
19 Participants
n=19 Participants
|
18 Participants
n=18 Participants
|
18 Participants
n=18 Participants
|
19 Participants
n=19 Participants
|
112 Participants
n=112 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=20 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=112 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=20 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=112 Participants
|
|
Country
Austria
|
1 Participants
n=20 Participants
|
0 Participants
n=18 Participants
|
2 Participants
n=19 Participants
|
1 Participants
n=18 Participants
|
1 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
5 Participants
n=112 Participants
|
|
Country
Germany
|
6 Participants
n=20 Participants
|
2 Participants
n=18 Participants
|
8 Participants
n=19 Participants
|
10 Participants
n=18 Participants
|
5 Participants
n=18 Participants
|
10 Participants
n=19 Participants
|
41 Participants
n=112 Participants
|
|
Country
Spain
|
7 Participants
n=20 Participants
|
8 Participants
n=18 Participants
|
4 Participants
n=19 Participants
|
3 Participants
n=18 Participants
|
5 Participants
n=18 Participants
|
4 Participants
n=19 Participants
|
31 Participants
n=112 Participants
|
|
Country
France
|
1 Participants
n=20 Participants
|
1 Participants
n=18 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=18 Participants
|
1 Participants
n=19 Participants
|
3 Participants
n=112 Participants
|
|
Country
United Kingdom
|
1 Participants
n=20 Participants
|
1 Participants
n=18 Participants
|
1 Participants
n=19 Participants
|
3 Participants
n=18 Participants
|
2 Participants
n=18 Participants
|
3 Participants
n=19 Participants
|
11 Participants
n=112 Participants
|
|
Country
Italy
|
4 Participants
n=20 Participants
|
6 Participants
n=18 Participants
|
4 Participants
n=19 Participants
|
1 Participants
n=18 Participants
|
5 Participants
n=18 Participants
|
1 Participants
n=19 Participants
|
21 Participants
n=112 Participants
|
|
Baseline Height (cm)
|
168.05 cm
STANDARD_DEVIATION 12.626 • n=20 Participants
|
165.62 cm
STANDARD_DEVIATION 12.348 • n=18 Participants
|
171.91 cm
STANDARD_DEVIATION 10.260 • n=19 Participants
|
174.78 cm
STANDARD_DEVIATION 6.632 • n=18 Participants
|
170.94 cm
STANDARD_DEVIATION 9.795 • n=18 Participants
|
171.16 cm
STANDARD_DEVIATION 9.929 • n=19 Participants
|
170.39 cm
STANDARD_DEVIATION 10.652 • n=112 Participants
|
|
Baseline Weight (kg)
|
74.25 kg
STANDARD_DEVIATION 16.151 • n=20 Participants
|
70.91 kg
STANDARD_DEVIATION 18.624 • n=18 Participants
|
78.45 kg
STANDARD_DEVIATION 21.893 • n=19 Participants
|
80.31 kg
STANDARD_DEVIATION 11.691 • n=18 Participants
|
83.26 kg
STANDARD_DEVIATION 24.383 • n=18 Participants
|
77.14 kg
STANDARD_DEVIATION 15.284 • n=19 Participants
|
77.34 kg
STANDARD_DEVIATION 18.470 • n=112 Participants
|
|
Baseline BMI (kg/m^2)
|
26.19 kg/m^2
STANDARD_DEVIATION 4.436 • n=20 Participants
|
25.60 kg/m^2
STANDARD_DEVIATION 4.813 • n=18 Participants
|
26.36 kg/m^2
STANDARD_DEVIATION 5.866 • n=19 Participants
|
26.34 kg/m^2
STANDARD_DEVIATION 4.013 • n=18 Participants
|
28.12 kg/m^2
STANDARD_DEVIATION 6.100 • n=18 Participants
|
26.30 kg/m^2
STANDARD_DEVIATION 4.912 • n=19 Participants
|
26.48 kg/m^2
STANDARD_DEVIATION 5.016 • n=112 Participants
|
|
Apomorphine naive at screening
N
|
1 Participants
n=20 Participants
|
2 Participants
n=18 Participants
|
5 Participants
n=19 Participants
|
2 Participants
n=18 Participants
|
2 Participants
n=18 Participants
|
1 Participants
n=19 Participants
|
13 Participants
n=112 Participants
|
|
Apomorphine naive at screening
Y
|
19 Participants
n=20 Participants
|
16 Participants
n=18 Participants
|
14 Participants
n=19 Participants
|
16 Participants
n=18 Participants
|
16 Participants
n=18 Participants
|
18 Participants
n=19 Participants
|
99 Participants
n=112 Participants
|
|
Total Daily Levodopa Dose Category (mg)
< 900 mg
|
15 Participants
n=20 Participants
|
13 Participants
n=18 Participants
|
15 Participants
n=19 Participants
|
14 Participants
n=18 Participants
|
15 Participants
n=18 Participants
|
14 Participants
n=19 Participants
|
86 Participants
n=112 Participants
|
|
Total Daily Levodopa Dose Category (mg)
>= 900 mg
|
5 Participants
n=20 Participants
|
5 Participants
n=18 Participants
|
4 Participants
n=19 Participants
|
4 Participants
n=18 Participants
|
3 Participants
n=18 Participants
|
5 Participants
n=19 Participants
|
26 Participants
n=112 Participants
|
|
Parkinson's disease duration Group
<=10 years
|
17 Participants
n=20 Participants
|
14 Participants
n=18 Participants
|
11 Participants
n=19 Participants
|
12 Participants
n=18 Participants
|
10 Participants
n=18 Participants
|
11 Participants
n=19 Participants
|
75 Participants
n=112 Participants
|
|
Parkinson's disease duration Group
>10 years
|
3 Participants
n=20 Participants
|
4 Participants
n=18 Participants
|
8 Participants
n=19 Participants
|
6 Participants
n=18 Participants
|
8 Participants
n=18 Participants
|
8 Participants
n=19 Participants
|
37 Participants
n=112 Participants
|
|
Movement Disorders Society Unified Parkinson Part III Score assessed prior to levodopa dosing at SV2
|
53.6 Units on a scale
STANDARD_DEVIATION 13.11 • n=20 Participants
|
50.6 Units on a scale
STANDARD_DEVIATION 14.74 • n=18 Participants
|
50.3 Units on a scale
STANDARD_DEVIATION 12.18 • n=19 Participants
|
50.1 Units on a scale
STANDARD_DEVIATION 10.33 • n=18 Participants
|
53.3 Units on a scale
STANDARD_DEVIATION 15.20 • n=18 Participants
|
48.6 Units on a scale
STANDARD_DEVIATION 13.36 • n=19 Participants
|
51.1 Units on a scale
STANDARD_DEVIATION 13.07 • n=112 Participants
|
|
Change in MDS-UPDRS Part III Score from Pre-dose to 30 minutes after levodopa dosing at SV2
|
-18.0 Units on a scale
STANDARD_DEVIATION 12.33 • n=19 Participants • safety population
|
-16.2 Units on a scale
STANDARD_DEVIATION 11.80 • n=18 Participants • safety population
|
-19.8 Units on a scale
STANDARD_DEVIATION 13.64 • n=19 Participants • safety population
|
-22.9 Units on a scale
STANDARD_DEVIATION 12.09 • n=18 Participants • safety population
|
-21.9 Units on a scale
STANDARD_DEVIATION 14.19 • n=17 Participants • safety population
|
-21.8 Units on a scale
STANDARD_DEVIATION 12.53 • n=19 Participants • safety population
|
-20.1 Units on a scale
STANDARD_DEVIATION 12.70 • n=110 Participants • safety population
|
PRIMARY outcome
Timeframe: Pre-dose to 90 minutes post-dose at Week 4 of each treatment period (Visit 3 and 6)Population: Part B mITT population
The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society. The summary score used in this study for the primary objective and primary efficacy endpoint is Part III motor examination score. Each Part III item has a 0-4 rating, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. 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. 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).
Outcome measures
| Measure |
SC (Subcutaneous Apomorphine)
n=61 Participants
subcutaneous apomorphine
|
APL (APL-130277)
n=62 Participants
APL-130277
|
|---|---|---|
|
Change From Pre-dose to 90 Mins. Post-dose in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Score After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).
|
-13.78 Units on a scale
Interval -16.65 to -10.9
|
-13.55 Units on a scale
Interval -16.39 to -10.7
|
SECONDARY outcome
Timeframe: Within 30 minutes post-dose and at 90 minutes post-dose at Week 4 of each treatment period (Visit 3 and 6)Population: Part B mITT population
Investigator will confirm whether subject is "OFF", Full "ON" or Partial "ON" , and note the time the subject changes from "OFF" to Partial "ON" or Full "ON". The Investigator will also record the subject "ON"/"OFF" status (binary variable, Yes / No) prior to performing each MDS-UPDRS Part III assessment. Durability of effect is defined as an Investigator confirmed full "ON" within 30 minutes post-dose and at 90 minutes post-dose, after 4 weeks of dosing in each PART B crossover period. Response rate = % of subjects that achived full "ON" within the timeframe
Outcome measures
| Measure |
SC (Subcutaneous Apomorphine)
n=61 Participants
subcutaneous apomorphine
|
APL (APL-130277)
n=62 Participants
APL-130277
|
|---|---|---|
|
Durability of Effect, Defined as an Investigator Confirmed Full "ON" Within 30 Minutes Post Dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).
|
18.03 Percentage of participants
|
17.74 Percentage of participants
|
SECONDARY outcome
Timeframe: After 8 weeks of treatment (Visit 6)Population: Part B mITT population
The TPQ assessment of subject treatment preference was changed from being based on a visual analogue scale or VAS (Q9b)) to a 5-point Likert scale (Q9a). Subject reported preference for APL or SC was based on question Q9a or Q9b combined. For Q9a, responses were dichotomized as follows for statistical analysis: preference for APL (responses of either definitely or somewhat prefer APL) versus no preference for APL (responses of no preference, or somewhat/definitely prefer sc apomorphine). The VAS score was similarly dichotomized as preference for APL (score of \>0 to 50) versus no preference for APL (-50 to 0). If a subject responded to both Q9a and Q9b, then Q9a only was used.
Outcome measures
| Measure |
SC (Subcutaneous Apomorphine)
n=72 Participants
subcutaneous apomorphine
|
APL (APL-130277)
APL-130277
|
|---|---|---|
|
Subject Preference for APL Treatment as Measured by the Subject Treatment Preference Questionnaire (TPQ), Planned After the Subject Had Completed Both APL-130277 and sc Apomorphine Treatment Regimens (Assessed In-clinic at Visit 6 of PART B)
|
72.2 % of participants
Interval 61.9 to 82.6
|
—
|
SECONDARY outcome
Timeframe: Week 4Population: Part B mITT population
Patients will confirm whether he/she is "OFF", Full "ON" or Partial "ON", and the staff will ask the subject to notify the staff when he/she changes from "OFF" to Partial "ON" or Full "ON" (binary variable, Yes / No) . Subject confirmed durability of effect is defined as subject confirmed full "ON" within 30 minutes post-dose and at 90 minutes post-dose, after 4 weeks of dosing in each crossover period (assessed in-clinic at V3 and V6 of PART B). Response rate = % subjects that achived full ON within the timeframe
Outcome measures
| Measure |
SC (Subcutaneous Apomorphine)
n=61 Participants
subcutaneous apomorphine
|
APL (APL-130277)
n=62 Participants
APL-130277
|
|---|---|---|
|
Subject Confirmed Durability of Effect, Defined as Subject Confirmed Full "ON" Within 30 Minutes Post-dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).
|
14.75 Percentage of participants
|
19.36 Percentage of participants
|
SECONDARY outcome
Timeframe: At Week 4 of each treatment period (Visit 3 and 6, or Early Termination)Population: Part B mITT population
The PGI-C is the patient reported outcome counterpart to the Clinical Global Impressions scale, (CGI), which was published in 1976 by the National Institute of Mental Health (US). It consists of one item taken from the CGI and adapted to the patient. The PGI-C is based on a 7-point scale, where a lower score is associated with higher symptom improvement. The scale is: Very much better Much better A little better No change A little worse Much worse Very much worse Subject improvement of "OFF" episodes is defined as very much better, much better or a little better at Week 4 in each PART B crossover period. Response rate= % of subjects who achieved improvement of "OFF" episodes
Outcome measures
| Measure |
SC (Subcutaneous Apomorphine)
n=70 Participants
subcutaneous apomorphine
|
APL (APL-130277)
n=71 Participants
APL-130277
|
|---|---|---|
|
Patient Global Impression of Change (PGI-C): Subject Improvement of "OFF" Episodes, Defined as Very Much Better, Much Better or a Little Better After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).
|
77.14 Percentage of participants
|
83.10 Percentage of participants
|
Adverse Events
Part A Dose Titration: APL (APL-130277)
Serious events: 0 serious events
Other events: 52 other events
Deaths: 0 deaths
Part A Dose Titration: SC (Subcutaneous Apomorphine)
Serious events: 1 serious events
Other events: 44 other events
Deaths: 0 deaths
Part B Treatment: APL (APL-130277)
Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths
Part B Treatment: SC (Subcutaneous Apomorphine)
Serious events: 1 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part A Dose Titration: APL (APL-130277)
n=102 participants at risk
Part A Dose Titration: APL (APL-130277)
|
Part A Dose Titration: SC (Subcutaneous Apomorphine)
n=97 participants at risk
Part A Dose Titration: SC (Subcutaneous Apomorphine)
|
Part B Treatment: APL (APL-130277)
n=71 participants at risk
Part B Treatment: APL (APL-130277)
|
Part B Treatment: SC (Subcutaneous Apomorphine)
n=70 participants at risk
Part B Treatment: SC (Subcutaneous Apomorphine)
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.00%
0/102 • 10 weeks (from first dose of study drug to last study visit)
|
1.0%
1/97 • Number of events 1 • 10 weeks (from first dose of study drug to last study visit)
|
0.00%
0/71 • 10 weeks (from first dose of study drug to last study visit)
|
0.00%
0/70 • 10 weeks (from first dose of study drug to last study visit)
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/102 • 10 weeks (from first dose of study drug to last study visit)
|
0.00%
0/97 • 10 weeks (from first dose of study drug to last study visit)
|
1.4%
1/71 • Number of events 1 • 10 weeks (from first dose of study drug to last study visit)
|
0.00%
0/70 • 10 weeks (from first dose of study drug to last study visit)
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/102 • 10 weeks (from first dose of study drug to last study visit)
|
0.00%
0/97 • 10 weeks (from first dose of study drug to last study visit)
|
0.00%
0/71 • 10 weeks (from first dose of study drug to last study visit)
|
1.4%
1/70 • Number of events 1 • 10 weeks (from first dose of study drug to last study visit)
|
Other adverse events
| Measure |
Part A Dose Titration: APL (APL-130277)
n=102 participants at risk
Part A Dose Titration: APL (APL-130277)
|
Part A Dose Titration: SC (Subcutaneous Apomorphine)
n=97 participants at risk
Part A Dose Titration: SC (Subcutaneous Apomorphine)
|
Part B Treatment: APL (APL-130277)
n=71 participants at risk
Part B Treatment: APL (APL-130277)
|
Part B Treatment: SC (Subcutaneous Apomorphine)
n=70 participants at risk
Part B Treatment: SC (Subcutaneous Apomorphine)
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
31.4%
32/102 • Number of events 53 • 10 weeks (from first dose of study drug to last study visit)
|
22.7%
22/97 • Number of events 31 • 10 weeks (from first dose of study drug to last study visit)
|
14.1%
10/71 • Number of events 25 • 10 weeks (from first dose of study drug to last study visit)
|
15.7%
11/70 • Number of events 21 • 10 weeks (from first dose of study drug to last study visit)
|
|
General disorders
Fatigue
|
5.9%
6/102 • Number of events 6 • 10 weeks (from first dose of study drug to last study visit)
|
10.3%
10/97 • Number of events 10 • 10 weeks (from first dose of study drug to last study visit)
|
5.6%
4/71 • Number of events 4 • 10 weeks (from first dose of study drug to last study visit)
|
5.7%
4/70 • Number of events 5 • 10 weeks (from first dose of study drug to last study visit)
|
|
General disorders
Injection site erythema
|
0.00%
0/102 • 10 weeks (from first dose of study drug to last study visit)
|
6.2%
6/97 • Number of events 9 • 10 weeks (from first dose of study drug to last study visit)
|
1.4%
1/71 • Number of events 1 • 10 weeks (from first dose of study drug to last study visit)
|
7.1%
5/70 • Number of events 5 • 10 weeks (from first dose of study drug to last study visit)
|
|
General disorders
Injection site haematoma
|
0.00%
0/102 • 10 weeks (from first dose of study drug to last study visit)
|
2.1%
2/97 • Number of events 2 • 10 weeks (from first dose of study drug to last study visit)
|
0.00%
0/71 • 10 weeks (from first dose of study drug to last study visit)
|
27.1%
19/70 • Number of events 23 • 10 weeks (from first dose of study drug to last study visit)
|
|
Injury, poisoning and procedural complications
Fall
|
0.98%
1/102 • Number of events 2 • 10 weeks (from first dose of study drug to last study visit)
|
1.0%
1/97 • Number of events 1 • 10 weeks (from first dose of study drug to last study visit)
|
5.6%
4/71 • Number of events 5 • 10 weeks (from first dose of study drug to last study visit)
|
1.4%
1/70 • Number of events 3 • 10 weeks (from first dose of study drug to last study visit)
|
|
Nervous system disorders
Dizziness
|
9.8%
10/102 • Number of events 15 • 10 weeks (from first dose of study drug to last study visit)
|
4.1%
4/97 • Number of events 4 • 10 weeks (from first dose of study drug to last study visit)
|
2.8%
2/71 • Number of events 2 • 10 weeks (from first dose of study drug to last study visit)
|
4.3%
3/70 • Number of events 3 • 10 weeks (from first dose of study drug to last study visit)
|
|
Nervous system disorders
Dyskinesia
|
7.8%
8/102 • Number of events 10 • 10 weeks (from first dose of study drug to last study visit)
|
7.2%
7/97 • Number of events 13 • 10 weeks (from first dose of study drug to last study visit)
|
11.3%
8/71 • Number of events 11 • 10 weeks (from first dose of study drug to last study visit)
|
20.0%
14/70 • Number of events 20 • 10 weeks (from first dose of study drug to last study visit)
|
|
Nervous system disorders
Somnolence
|
8.8%
9/102 • Number of events 9 • 10 weeks (from first dose of study drug to last study visit)
|
13.4%
13/97 • Number of events 18 • 10 weeks (from first dose of study drug to last study visit)
|
4.2%
3/71 • Number of events 3 • 10 weeks (from first dose of study drug to last study visit)
|
5.7%
4/70 • Number of events 4 • 10 weeks (from first dose of study drug to last study visit)
|
|
Respiratory, thoracic and mediastinal disorders
Yawning
|
2.9%
3/102 • Number of events 3 • 10 weeks (from first dose of study drug to last study visit)
|
5.2%
5/97 • Number of events 8 • 10 weeks (from first dose of study drug to last study visit)
|
0.00%
0/71 • 10 weeks (from first dose of study drug to last study visit)
|
1.4%
1/70 • Number of events 1 • 10 weeks (from first dose of study drug to last study visit)
|
|
Vascular disorders
Orthostatic hypotension
|
3.9%
4/102 • Number of events 5 • 10 weeks (from first dose of study drug to last study visit)
|
5.2%
5/97 • Number of events 5 • 10 weeks (from first dose of study drug to last study visit)
|
4.2%
3/71 • Number of events 4 • 10 weeks (from first dose of study drug to last study visit)
|
5.7%
4/70 • Number of events 5 • 10 weeks (from first dose of study drug to last study visit)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER