Trial Outcomes & Findings for 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 (NCT NCT03292016)
NCT ID: NCT03292016
Last Updated: 2020-08-13
Results Overview
Dose normalized maximum observed plasma concentration (Cmax)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
8 participants
Primary outcome timeframe
Day 1
Results posted on
2020-08-13
Participant Flow
Participant milestones
| Measure |
APL-130277, Then APOKYN, Then APO-go
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.
|
APL-130277, Then APO-go, Then APOKYN
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.
|
APOKYN, Then APL-130277, Then APO-go
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.
|
APOKYN, Then APO-go, Then APL-130277
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.
|
APO-go, Then APL-130277, Then APOKYN
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.
|
APO-go, Then APOKYN, Then APL-130277
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.
|
|---|---|---|---|---|---|---|
|
First Intervention
STARTED
|
1
|
1
|
2
|
1
|
1
|
2
|
|
First Intervention
COMPLETED
|
1
|
1
|
2
|
1
|
1
|
2
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
First Washout
STARTED
|
1
|
1
|
2
|
1
|
1
|
2
|
|
First Washout
COMPLETED
|
1
|
1
|
2
|
1
|
1
|
2
|
|
First Washout
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Second Intervention
STARTED
|
1
|
1
|
2
|
1
|
1
|
2
|
|
Second Intervention
COMPLETED
|
1
|
1
|
2
|
1
|
1
|
2
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Second Washout
STARTED
|
1
|
1
|
2
|
1
|
1
|
2
|
|
Second Washout
COMPLETED
|
1
|
0
|
2
|
1
|
1
|
2
|
|
Second Washout
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Third Intervention
STARTED
|
1
|
0
|
2
|
1
|
1
|
2
|
|
Third Intervention
COMPLETED
|
1
|
0
|
2
|
1
|
1
|
2
|
|
Third Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
APL-130277, Then APOKYN, Then APO-go
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.
|
APL-130277, Then APO-go, Then APOKYN
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.
|
APOKYN, Then APL-130277, Then APO-go
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.
|
APOKYN, Then APO-go, Then APL-130277
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.
|
APO-go, Then APL-130277, Then APOKYN
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.
|
APO-go, Then APOKYN, Then APL-130277
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.
|
|---|---|---|---|---|---|---|
|
Second Washout
Adverse Event
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
APL-130277, Then APOKYN, Then APO-go
n=1 Participants
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.
|
APL-130277, Then APO-go, Then APOKYN
n=1 Participants
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.
|
APOKYN, Then APL-130277, Then APO-go
n=2 Participants
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.
|
APOKYN, Then APO-go, Then APL-130277
n=1 Participants
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.
|
APO-go, Then APL-130277, Then APOKYN
n=1 Participants
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.
|
APO-go, Then APOKYN, Then APL-130277
n=2 Participants
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
n=8 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
BMI (kg/m2) at Baseline
|
28.9 kg/m^2
n=5 Participants
|
23.9 kg/m^2
n=7 Participants
|
28.1 kg/m^2
STANDARD_DEVIATION 3.111 • n=5 Participants
|
23.8 kg/m^2
n=4 Participants
|
26.7 kg/m^2
n=21 Participants
|
23.8 kg/m^2
STANDARD_DEVIATION 3.111 • n=10 Participants
|
25.89 kg/m^2
STANDARD_DEVIATION 2.826 • n=115 Participants
|
|
ON State Mod. Hoehn & Yahr Score
|
2 Score
n=5 Participants
|
2 Score
n=7 Participants
|
2.5 Score
STANDARD_DEVIATION 0 • n=5 Participants
|
2.5 Score
n=4 Participants
|
3 Score
n=21 Participants
|
2.5 Score
STANDARD_DEVIATION 0.707 • n=10 Participants
|
2.44 Score
STANDARD_DEVIATION 0.417 • n=115 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
5 Participants
n=115 Participants
|
|
Age, Continuous
|
75 Years
n=5 Participants
|
51 Years
n=7 Participants
|
67.5 Years
STANDARD_DEVIATION 9.19 • n=5 Participants
|
67 Years
n=4 Participants
|
73 Years
n=21 Participants
|
68.5 Years
STANDARD_DEVIATION 9.19 • n=10 Participants
|
67.3 Years
STANDARD_DEVIATION 8.7 • n=115 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
6 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
8 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
8 Participants
n=115 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Country
United States
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
8 Participants
n=115 Participants
|
|
Height (cm) at Baseline
|
172.7 cm
n=5 Participants
|
157.5 cm
n=7 Participants
|
174.95 cm
STANDARD_DEVIATION 11.243 • n=5 Participants
|
175.3 cm
n=4 Participants
|
177.8 cm
n=21 Participants
|
171.25 cm
STANDARD_DEVIATION 19.445 • n=10 Participants
|
171.96 cm
STANDARD_DEVIATION 10.545 • n=115 Participants
|
|
Body Weight (kg) at Baseline
|
86.3 kg
n=5 Participants
|
59.4 kg
n=7 Participants
|
86.7 kg
STANDARD_DEVIATION 20.506 • n=5 Participants
|
73 kg
n=4 Participants
|
84.4 kg
n=21 Participants
|
71.2 kg
STANDARD_DEVIATION 25.032 • n=10 Participants
|
77.36 kg
STANDARD_DEVIATION 15.895 • n=115 Participants
|
|
Mini-Mental Status Total Score
|
30 Score
n=5 Participants
|
30 Score
n=7 Participants
|
26.5 Score
STANDARD_DEVIATION 2.12 • n=5 Participants
|
25 Score
n=4 Participants
|
27 Score
n=21 Participants
|
27.5 Score
STANDARD_DEVIATION 3.54 • n=10 Participants
|
27.5 Score
STANDARD_DEVIATION 2.33 • n=115 Participants
|
|
Child-bearing potential
Yes
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
|
Child-bearing potential
No
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
|
Child-bearing potential
N/A
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
6 Participants
n=115 Participants
|
|
Smoking Status
Has never smoked
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
6 Participants
n=115 Participants
|
|
Smoking Status
Former Smoker
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: Day 1Dose normalized maximum observed plasma concentration (Cmax)
Outcome measures
| Measure |
APL-130277, Sublingual Thin Film
n=8 Participants
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=7 Participants
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=8 Participants
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
|
0.281 (ng/mL)/(mg)
Interval 0.191 to 0.413
|
2.29 (ng/mL)/(mg)
Interval 1.46 to 3.59
|
2.74 (ng/mL)/(mg)
Interval 1.82 to 4.13
|
PRIMARY outcome
Timeframe: Day 1Population: Tmax summary statistics were summarized by dose levels and the inferential statistics was done across all dose levels.
Time from dosing to Cmax, observed by inspection of individual subject plots of plasma concentration versus time.
Outcome measures
| Measure |
APL-130277, Sublingual Thin Film
n=8 Participants
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=7 Participants
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=8 Participants
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Observed Time of the Maximum Concentration (Tmax)
APL 20 mg, APOKYN 3 mg, and APO-go 3 mg
|
0.75 hour
Interval 0.52 to 0.75
|
0.38 hour
Interval 0.25 to 0.5
|
0.38 hour
Interval 0.25 to 0.5
|
|
Observed Time of the Maximum Concentration (Tmax)
APL 25 mg, APOKYN 4 mg, and APO-go 4 mg
|
0.63 hour
Interval 0.25 to 1.02
|
0.25 hour
Interval 0.25 to 0.25
|
0.26 hour
Interval 0.25 to 0.27
|
|
Observed Time of the Maximum Concentration (Tmax)
APL 30 mg, APOKYN 5 mg, and APO-go 5 mg
|
0.75 hour
Interval 0.5 to 1.0
|
0.38 hour
Interval 0.25 to 0.5
|
0.25 hour
Interval 0.25 to 0.5
|
PRIMARY outcome
Timeframe: Day 1area under the concentration-time curve from time zero to the last measurable plasma concentration-time curve using the linear up log down trapezoidal rule.
Outcome measures
| Measure |
APL-130277, Sublingual Thin Film
n=8 Participants
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=7 Participants
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=8 Participants
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Area Under the Concentration- Time Curve (AUC Last)
|
0.500 (hxng/mL)/(mg)
Interval 0.344 to 0.726
|
2.91 (hxng/mL)/(mg)
Interval 1.97 to 4.3
|
3.00 (hxng/mL)/(mg)
Interval 2.05 to 4.39
|
PRIMARY outcome
Timeframe: Day 1area under the concentration-time curve from time zero extrapolated to infinity using the linear up log down trapezoidal rule.
Outcome measures
| Measure |
APL-130277, Sublingual Thin Film
n=8 Participants
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=7 Participants
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=8 Participants
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Area Under the Concentration- Time Curve (AUC Inf)
|
0.52 (hxng/mL)/(mg)
Interval 0.36 to 0.76
|
2.97 (hxng/mL)/(mg)
Interval 2.01 to 4.39
|
3.04 (hxng/mL)/(mg)
Interval 2.08 to 4.45
|
PRIMARY outcome
Timeframe: Day 1Population: MRT was summarized by dose level
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.
Outcome measures
| Measure |
APL-130277, Sublingual Thin Film
n=8 Participants
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=6 Participants
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=7 Participants
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Mean Residence Time (MRT)
APL 20 mg, APOKYN 3 mg, and APO-go 3 mg
|
1.69 h
Geometric Coefficient of Variation 5.2
|
1.44 h
Geometric Coefficient of Variation 4.3
|
1.21 h
Geometric Coefficient of Variation 19.3
|
|
Mean Residence Time (MRT)
APL 25 mg, APOKYN 4 mg, and APO-go 4 mg
|
1.83 h
Geometric Coefficient of Variation 41.5
|
1.70 h
Geometric Coefficient of Variation 13.8
|
1.51 h
Geometric Coefficient of Variation 19.0
|
|
Mean Residence Time (MRT)
APL 30 mg, APOKYN 5 mg, and APO-go 5 mg
|
2.15 h
Geometric Coefficient of Variation 15.9
|
1.23 h
Geometric Coefficient of Variation 3.4
|
1.08 h
Geometric Coefficient of Variation 35.4
|
PRIMARY outcome
Timeframe: Day 1Population: Metabolite/Parent Cmax summarized by dose level
Metabolite (apomorphine sulfate) to Parent exposure ratio, Cmax, corrected for molecular weight differences.
Outcome measures
| Measure |
APL-130277, Sublingual Thin Film
n=8 Participants
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=6 Participants
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=7 Participants
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Metabolite/Parent (M/P) Drug Concentration Ratio -Cmax
APL 20 mg, APOKYN 3 mg and APO-go 3 mg
|
61.6 no unit
Geometric Coefficient of Variation 28.8
|
15.2 no unit
Geometric Coefficient of Variation 48.9
|
11.5 no unit
Geometric Coefficient of Variation 4.0
|
|
Metabolite/Parent (M/P) Drug Concentration Ratio -Cmax
APL 25 mg, APOKYN 4 mg and APO-go 4 mg
|
32.0 no unit
Geometric Coefficient of Variation 157.1
|
9.0 no unit
Geometric Coefficient of Variation 149.3
|
7.1 no unit
Geometric Coefficient of Variation 240.3
|
|
Metabolite/Parent (M/P) Drug Concentration Ratio -Cmax
APL 30 mg, APOKYN 5 mg and APO-go 5 mg
|
61.2 no unit
Geometric Coefficient of Variation 87.0
|
13.7 no unit
Geometric Coefficient of Variation 8.2
|
11.3 no unit
Geometric Coefficient of Variation 47.6
|
PRIMARY outcome
Timeframe: Day 1Population: CL/F summarized by dose level
Apparent total clearance of the drug from plasma extravascular administration, calculated as Dose/AUCinf.
Outcome measures
| Measure |
APL-130277, Sublingual Thin Film
n=8 Participants
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=6 Participants
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=7 Participants
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F)
APL 20 mg, APOKYN 3 mg and APO-go 3 mg
|
2766.9 L/h
Geometric Coefficient of Variation 52.4
|
407.9 L/h
Geometric Coefficient of Variation 33.3
|
375.6 L/h
Geometric Coefficient of Variation 32.2
|
|
Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F)
APL 25 mg, APOKYN 4 mg and APO-go 4 mg
|
1097.8 L/h
Geometric Coefficient of Variation 99.5
|
250.2 L/h
Geometric Coefficient of Variation 140.6
|
253.7 L/h
Geometric Coefficient of Variation 169.6
|
|
Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F)
APL 30 mg, APOKYN 5 mg and APO-go 5 mg
|
1952.1 L/h
Geometric Coefficient of Variation 44.3
|
350.6 L/h
Geometric Coefficient of Variation 4.0
|
299.2 L/h
Geometric Coefficient of Variation 41.0
|
PRIMARY outcome
Timeframe: Day 1Population: V/F summarized by dose level
Apparent volume of distribution after extravascular administration, calculated as Dose/(AUCinf \* λz).
Outcome measures
| Measure |
APL-130277, Sublingual Thin Film
n=8 Participants
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=8 Participants
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=7 Participants
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Apparent Volume of Distribution After Non-intravenous Administration (V/F)
APL 25 mg, APOKYN 4 mg and APO-go 4 mg
|
1733.4 L
Geometric Coefficient of Variation 52.8
|
420.8 L
Geometric Coefficient of Variation 193.7
|
372.2 L
Geometric Coefficient of Variation 231.1
|
|
Apparent Volume of Distribution After Non-intravenous Administration (V/F)
APL 30 mg, APOKYN 5 mg and APO-go 5 mg
|
3419.5 L
Geometric Coefficient of Variation 67.4
|
452.0 L
Geometric Coefficient of Variation 14.7
|
324.2 L
Geometric Coefficient of Variation 73.7
|
|
Apparent Volume of Distribution After Non-intravenous Administration (V/F)
APL 20 mg, APOKYN 3 mg and APO-go 3 mg
|
4440.2 L
Geometric Coefficient of Variation 72.0
|
577.5 L
Geometric Coefficient of Variation 44.3
|
469.3 L
Geometric Coefficient of Variation 19.1
|
PRIMARY outcome
Timeframe: Day 1Population: Terminal-phase half-life summarized by dose level
Terminal phase half-life, as calculated by the following equation: t½ = ln(2)/λz.
Outcome measures
| Measure |
APL-130277, Sublingual Thin Film
n=8 Participants
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=8 Participants
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=7 Participants
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Terminal-phase Half-life (t½)
APL 20 mg, APOKYN 3 mg and APO-go 3 mg
|
1.11 h
Geometric Coefficient of Variation 15.6
|
0.98 h
Geometric Coefficient of Variation 9.9
|
0.87 h
Geometric Coefficient of Variation 12.6
|
|
Terminal-phase Half-life (t½)
APL 25 mg, APOKYN 4 mg and APO-go 4 mg
|
1.09 h
Geometric Coefficient of Variation 34.3
|
1.17 h
Geometric Coefficient of Variation 20.6
|
1.02 h
Geometric Coefficient of Variation 19.7
|
|
Terminal-phase Half-life (t½)
APL 30 mg, APOKYN 5 mg and APO-go 5 mg
|
1.21 h
Geometric Coefficient of Variation 20.5
|
0.89 h
Geometric Coefficient of Variation 18.7
|
0.75 h
Geometric Coefficient of Variation 35.5
|
PRIMARY outcome
Timeframe: Day 1Population: terminal-phase rate constant summarized by dose level
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.
Outcome measures
| Measure |
APL-130277, Sublingual Thin Film
n=8 Participants
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=6 Participants
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=7 Participants
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Terminal-phase Rate Constant ( λz)
APL 20 mg, APOKYN 3 mg and APO-go 3 mg
|
0.62 /h
Geometric Coefficient of Variation 15.6
|
0.71 /h
Geometric Coefficient of Variation 9.9
|
0.80 /h
Geometric Coefficient of Variation 12.6
|
|
Terminal-phase Rate Constant ( λz)
APL 25 mg, APOKYN 4 mg and APO-go 4 mg
|
0.63 /h
Geometric Coefficient of Variation 34.3
|
0.59 /h
Geometric Coefficient of Variation 20.6
|
0.68 /h
Geometric Coefficient of Variation 19.7
|
|
Terminal-phase Rate Constant ( λz)
APL 30 mg, APOKYN 5 mg and APO-go 5 mg
|
0.57 /h
Geometric Coefficient of Variation 20.5
|
0.78 /h
Geometric Coefficient of Variation 18.7
|
0.92 /h
Geometric Coefficient of Variation 35.5
|
PRIMARY outcome
Timeframe: Day 1Population: Metabolite/Parent (M/P) drug concentration Ratio -AUC last summarized by dose level
Metabolite (apomorphine sulfate) to Parent exposure ratio, AUClast, corrected for molecular weight differences.
Outcome measures
| Measure |
APL-130277, Sublingual Thin Film
n=8 Participants
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=8 Participants
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=7 Participants
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Metabolite/Parent (M/P) Drug Concentration Ratio -AUC Last
APL 20 mg, APOKYN 3 mg and APO-go 3 mg
|
98.16 no unit
Geometric Coefficient of Variation 6.4
|
36.22 no unit
Geometric Coefficient of Variation 3.0
|
32.19 no unit
Geometric Coefficient of Variation 9.9
|
|
Metabolite/Parent (M/P) Drug Concentration Ratio -AUC Last
APL 25 mg, APOKYN 4 mg and APO-go 4 mg
|
45.79 no unit
Geometric Coefficient of Variation 169.9
|
18.70 no unit
Geometric Coefficient of Variation 162.8
|
16.27 no unit
Geometric Coefficient of Variation 221.6
|
|
Metabolite/Parent (M/P) Drug Concentration Ratio -AUC Last
APL 30 mg, APOKYN 5 mg and APO-go 5 mg
|
98.07 no unit
Geometric Coefficient of Variation 55.4
|
33.63 no unit
Geometric Coefficient of Variation 6.2
|
26.22 no unit
Geometric Coefficient of Variation 43.6
|
Adverse Events
APL-130277, Sublingual Thin Film
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Subcutaneous APOKYN
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Subcutaneous APO-go
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
APL-130277, Sublingual Thin Film
n=8 participants at risk
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=7 participants at risk
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=8 participants at risk
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Fall
|
12.5%
1/8 • Number of events 1 • 16 days
|
0.00%
0/7 • 16 days
|
0.00%
0/8 • 16 days
|
|
Injury, poisoning and procedural complications
Rib fracture
|
12.5%
1/8 • Number of events 1 • 16 days
|
0.00%
0/7 • 16 days
|
0.00%
0/8 • 16 days
|
|
Injury, poisoning and procedural complications
Splenic rupture
|
12.5%
1/8 • Number of events 1 • 16 days
|
0.00%
0/7 • 16 days
|
0.00%
0/8 • 16 days
|
Other adverse events
| Measure |
APL-130277, Sublingual Thin Film
n=8 participants at risk
APL-130277, sublingual thin film, once daily
|
Subcutaneous APOKYN
n=7 participants at risk
Subcutaneous APOKYN, once daily
|
Subcutaneous APO-go
n=8 participants at risk
Subcutaneous APO-go, once daily
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8 • Number of events 1 • 16 days
|
14.3%
1/7 • Number of events 1 • 16 days
|
25.0%
2/8 • Number of events 2 • 16 days
|
|
General disorders
Injection site bruising
|
0.00%
0/8 • 16 days
|
0.00%
0/7 • 16 days
|
12.5%
1/8 • Number of events 1 • 16 days
|
|
Nervous system disorders
Dyskinesia
|
0.00%
0/8 • 16 days
|
0.00%
0/7 • 16 days
|
12.5%
1/8 • Number of events 1 • 16 days
|
|
Nervous system disorders
Somnolence
|
0.00%
0/8 • 16 days
|
14.3%
1/7 • Number of events 1 • 16 days
|
0.00%
0/8 • 16 days
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/8 • 16 days
|
0.00%
0/7 • 16 days
|
12.5%
1/8 • Number of events 1 • 16 days
|
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