Trial Outcomes & Findings for A Study to Examine APL-130277 in Patients With Parkinson's Disease (NCT NCT02228590)
NCT ID: NCT02228590
Last Updated: 2020-07-30
Results Overview
Clinical confirmation of an 'OFF' state was assessed prior to dosing and confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The first full 'ON' dose was defined as the earliest dose in which a patient achieved a full 'ON' state as assessed by the Investigator. The percentage of patients who achieved their first full 'ON' is presented for each timepoint, regardless of the dose received, and for the study overall (i.e. all post-dose timepoints).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.
Results posted on
2020-07-30
Participant Flow
Patients with moderate to advanced Idiopathic Parkinson's Disease (PD) were recruited to this study in 4 study sites in the United States from August 2014. The study was completed in November 2014.
23 patients were screened, 20 were assigned to treatment and 1 withdrew consent prior to treatment. 19 received APL-130277 APL-130277 sublingual film for the acute intermittent treatement of OFF episodes in PD patients . Doses studied were 10, 15, 20, 25 and 30 milligrams (mg).
Participant milestones
| Measure |
APL-130277
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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|---|---|
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Overall Study
STARTED
|
20
|
|
Overall Study
COMPLETED
|
19
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
APL-130277
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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|---|---|
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Overall Study
Withdrawal by Subject
|
1
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Baseline Characteristics
A Study to Examine APL-130277 in Patients With Parkinson's Disease
Baseline characteristics by cohort
| Measure |
APL-130277
n=19 Participants
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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|---|---|
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Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
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Age, Categorical
Between 18 and 65 years
|
12 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=93 Participants
|
|
Age, Continuous
|
61.5 years
STANDARD_DEVIATION 8.71 • n=93 Participants
|
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Sex: Female, Male
Female
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5 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
16 Participants
n=93 Participants
|
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Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
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Region of Enrollment
United States
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19 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.Population: The modified Intent-to-Treat (mITT) Population consisted of all patients who received at least 1 dose of study medication.
Clinical confirmation of an 'OFF' state was assessed prior to dosing and confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The first full 'ON' dose was defined as the earliest dose in which a patient achieved a full 'ON' state as assessed by the Investigator. The percentage of patients who achieved their first full 'ON' is presented for each timepoint, regardless of the dose received, and for the study overall (i.e. all post-dose timepoints).
Outcome measures
| Measure |
APL-130277
n=19 Participants
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
Overall
|
78.9 percentage of participants
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The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
15 minutes post-dose
|
31.6 percentage of participants
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The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
30 minutes post-dose
|
78.9 percentage of participants
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The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
45 minutes post-dose
|
68.4 percentage of participants
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The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
60 minutes post-dose
|
68.4 percentage of participants
|
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The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
90 minutes post-dose
|
47.4 percentage of participants
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PRIMARY outcome
Timeframe: At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.Population: The mITT Population consisted of all patients who received at least 1 dose of study medication, and data is presented for patients who turned 'ON'.
Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The time to the full 'ON' state from the time of dosing in minutes was calculated from timings noted by the Investigator and recorded in the electronic case report form (eCRF). The mean time taken for a patient to reach their first full 'ON' state following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.
Outcome measures
| Measure |
APL-130277
n=19 Participants
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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|---|---|
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Time to 'ON' State From Time of Dosing of APL-130277
|
24.0 minutes
Standard Deviation 7.61
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PRIMARY outcome
Timeframe: At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.Population: The mITT Population consisted of all patients who received at least 1 dose of study medication, and data is presented for patients who turned 'ON'.
Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The duration of the 'ON' response was defined as the length of time in which a patient was confirmed 'ON' within a dose, and was calculated from the time noted by the Investigator and recorded in the eCRF. The mean duration of the first full 'ON' response following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.
Outcome measures
| Measure |
APL-130277
n=19 Participants
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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|---|---|
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Duration of 'ON' Response From Time of Dosing of APL-130277
|
50.0 minutes
Standard Deviation 19.36
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PRIMARY outcome
Timeframe: At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.Population: The mITT Population consisted of all patients who received at least 1 dose of study medication.
Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. For the overall study, the percentage of patients who completed the trial, and who experienced an 'ON' episode is presented.
Outcome measures
| Measure |
APL-130277
n=19 Participants
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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|---|---|
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Percentage of Patients Who Completed the Trial and Experienced an 'ON' Episode
|
78.9 percentage of participants
|
PRIMARY outcome
Timeframe: Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.Population: Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.
The mean Cmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available. Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, with a lower limit of quantification of 0.020 nanograms per millilitre (ng/mL).
Outcome measures
| Measure |
APL-130277
n=8 Participants
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
10 mg APL-130277 Dose 1 Day 1
|
2.01 ng/mL
Standard Deviation 0.914
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Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
15 mg APL-130277 Dose 2 Day 1
|
2.52 ng/mL
Standard Deviation 1.04
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|
Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
10 mg APL-130277 Dose 1 Day 2
|
4.18 ng/mL
Standard Deviation NA
No SD is available as data is for a single patient.
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Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
20 mg APL-130277 Dose 1 Day 2
|
3.82 ng/mL
Standard Deviation 1.81
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Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
25 mg APL-130277 Dose 2 Day 2
|
4.84 ng/mL
Standard Deviation NA
No SD available due to small number of patients analysed for this dose
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Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
20 mg APL-130277 Dose 1 Day 3
|
2.82 ng/mL
Standard Deviation 1.38
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Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
25 mg APL-130277 Dose 1 Day 3
|
12.3 ng/mL
Standard Deviation NA
No SD is available as data is for a single patient.
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Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
30 mg APL-130277 Dose 1 Day 3
|
4.22 ng/mL
Standard Deviation NA
No SD is available as data is for a single patient.
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Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
25 mg APL-130277 Dose 2 Day 3
|
4.84 ng/mL
Standard Deviation 2.99
|
PRIMARY outcome
Timeframe: Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.Population: Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.
The median Tmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available. Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.
Outcome measures
| Measure |
APL-130277
n=8 Participants
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)
10 mg APL-130277 Dose 1 Day 1
|
60.0 minutes
Interval 45.0 to 90.0
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PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)
15 mg APL-130277 Dose 2 Day 1
|
35.0 minutes
Interval 24.0 to 90.0
|
|
PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)
20 mg APL-130277 Dose 1 Day 2
|
47.0 minutes
Interval 25.0 to 61.0
|
|
PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)
20 mg APL-130277 Dose 1 Day 3
|
56.5 minutes
Interval 30.0 to 61.0
|
|
PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)
25 mg APL-130277 Dose 2 Day 3
|
45.0 minutes
Interval 28.0 to 90.0
|
PRIMARY outcome
Timeframe: Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.Population: Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.
The mean Tlast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available. Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.
Outcome measures
| Measure |
APL-130277
n=8 Participants
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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|---|---|
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PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
10 mg APL-130277 Dose 1 Day 1
|
89.4 minutes
Standard Deviation 8.63
|
|
PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
15 mg APL-130277 Dose 2 Day 1
|
90.8 minutes
Standard Deviation 2.04
|
|
PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
10 mg APL-130277 Dose 1 Day 2
|
95.0 minutes
Standard Deviation NA
No SD is available as data is for a single patient.
|
|
PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
20 mg APL-130277 Dose 1 Day 2
|
88.9 minutes
Standard Deviation 15.1
|
|
PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
25 mg APL-130277 Dose 2 Day 2
|
94.0 minutes
Standard Deviation NA
No SD available due to small number patients analysed for this dose.
|
|
PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
20 mg APL-130277 Dose 1 Day 3
|
95.2 minutes
Standard Deviation 6.40
|
|
PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
25 mg APL-130277 Dose 1 Day 3
|
102 minutes
Standard Deviation NA
No SD is available as data is for a single patient
|
|
PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
30 mg APL-130277 Dose 1 Day 3
|
92.0 minutes
Standard Deviation NA
No SD is available as data is for a single patient
|
|
PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
25 mg APL-130277 Dose 2 Day 3
|
75.7 minutes
Standard Deviation 24.8
|
PRIMARY outcome
Timeframe: Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.Population: Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.
The mean AUC0-90 values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available. Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.
Outcome measures
| Measure |
APL-130277
n=8 Participants
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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|---|---|
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PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
10 mg APL-130277 Dose 1 Day 1
|
132 min*ng/mL
Standard Deviation 42.8
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
15 mg APL-130277 Dose 2 Day 1
|
149 min*ng/mL
Standard Deviation 57.2
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
10 mg APL-130277 Dose 1 Day 2
|
269 min*ng/mL
Standard Deviation NA
No SD is available as data is for a single patient
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
20 mg APL-130277 Dose 1 Day 2
|
216 min*ng/mL
Standard Deviation 127
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
25 mg APL-130277 Dose 2 Day 2
|
266 min*ng/mL
Standard Deviation NA
No SD available due to small number patients analysed for this dose.
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
20 mg APL-130277 Dose 1 Day 3
|
170 min*ng/mL
Standard Deviation 77.2
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
25 mg APl-130277 Dose 1 Day 3
|
507 min*ng/mL
Standard Deviation NA
No SD is available as data is for a single patient
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
30 mg APL-130277 Dose 1 Day 3
|
197 min*ng/mL
Standard Deviation NA
No SD is available as data is for a single patient
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
25 mg APL-130277 Dose 2 Day 3
|
367 min*ng/mL
Standard Deviation NA
No SD available due to small number patients analysed for this dose.
|
PRIMARY outcome
Timeframe: Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.Population: Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.
The mean AUClast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available. Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL. The AUClast was calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method).
Outcome measures
| Measure |
APL-130277
n=8 Participants
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
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|---|---|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
10 mg APL-130277 Dose 1 Day 1
|
121 min*ng/mL
Standard Deviation 52.2
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
15 mg APL-130277 Dose 2 Day 1
|
151 min*ng/mL
Standard Deviation 58.4
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
10 mg APL-130277 Dose 1 Day 2
|
279 min*ng/mL
Standard Deviation NA
No SD is available as data is for a single patient
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
20 mg APL-130277 Dose 1 Day 2
|
203 min*ng/mL
Standard Deviation 122
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
25 mg APL-130277 Dose 2 Day 2
|
277 min*ng/mL
Standard Deviation NA
No SD available due to small number patients analysed for this dose.
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
20 mg APL-130277 Dose 1 Day 3
|
179 min*ng/mL
Standard Deviation 69.2
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
25 mg APl-130277 Dose 1 Day 3
|
566 min*ng/mL
Standard Deviation NA
No SD is available as data is for a single patient
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
30 mg APl-130277 Dose 1 Day 3
|
206 min*ng/mL
Standard Deviation NA
No SD is available as data is for a single patient
|
|
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
25 mg APL-130277 Dose 2 Day 3
|
268 min*ng/mL
Standard Deviation 193
|
SECONDARY outcome
Timeframe: At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.Population: The mITT Population consisted of all patients who received at least 1 dose of study medication.
The Motor Function section (Section III) of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The percent change in the MDS-UPDRS Section III score from pre-dose to the first full ON dose or last dose for non-responders is presented. A negative change from baseline indicates an improvement.
Outcome measures
| Measure |
APL-130277
n=19 Participants
At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.
|
|---|---|
|
Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment
Change from Pre-Dose to 15 min Post-Dose
|
-27.9 percent of change
Standard Deviation 20.72
|
|
Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment
Change from Pre-Dose to 30 min Post-Dose
|
-34.4 percent of change
Standard Deviation 19.04
|
|
Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment
Change from Pre-Dose to 45 min Post-Dose
|
-35.6 percent of change
Standard Deviation 20.03
|
|
Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment
Change from Pre-Dose to 60 min Post-Dose
|
-32.4 percent of change
Standard Deviation 23.20
|
|
Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment
Change from Pre-Dose to 90 min Post-Dose
|
-23.8 percent of change
Standard Deviation 26.14
|
Adverse Events
APL-130277
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
APL-130277
n=19 participants at risk
At each of 3 dosing visits patients were assessed in a practically defined 'OFF' state after withholding their usual PD medications the night before and APL-130277 sublingual film was administered initially at 10 mg. If the patient did not convert to a full 'ON' state within 3 hours from initial dosing and did not experience orthostatic
|
|---|---|
|
Gastrointestinal disorders
Dysphagia
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
Other adverse events
| Measure |
APL-130277
n=19 participants at risk
At each of 3 dosing visits patients were assessed in a practically defined 'OFF' state after withholding their usual PD medications the night before and APL-130277 sublingual film was administered initially at 10 mg. If the patient did not convert to a full 'ON' state within 3 hours from initial dosing and did not experience orthostatic
|
|---|---|
|
Gastrointestinal disorders
nausea
|
21.1%
4/19 • Number of events 8 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
vomiting
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
General disorders
chest discomfort
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
General disorders
chest pain
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
General disorders
fatigue
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
muscle spasms
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
muscuar weakness
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
musculoskeletal stiffness
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
neck pain
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Nervous system disorders
balance disorder
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Nervous system disorders
dizziness
|
36.8%
7/19 • Number of events 8 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Nervous system disorders
headache
|
10.5%
2/19 • Number of events 3 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Nervous system disorders
paraesthesia
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Nervous system disorders
somnolence
|
31.6%
6/19 • Number of events 8 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Nervous system disorders
tremor
|
5.3%
1/19 • Number of events 2 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Psychiatric disorders
apathy
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Psychiatric disorders
nervousness
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
yawning
|
15.8%
3/19 • Number of events 4 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
upper-airway cough syndrome
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Skin and subcutaneous tissue disorders
hyperhidrosis
|
10.5%
2/19 • Number of events 2 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Vascular disorders
hot flush
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Vascular disorders
orthostatic hypotension
|
5.3%
1/19 • Number of events 1 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
|
Vascular disorders
peripheral coldness
|
5.3%
1/19 • Number of events 2 • Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.
Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.
|
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 mult-center publication; provided however, if a mult-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