Parkinson's Disease
Conditions
Keywords
Parkinson's Disease
Brief summary
The primary objective of this study is to evaluate the efficacy, tolerability and safety of single treatments of APL-130277 in 16 patients with Parkinson's Disease (PD)
Interventions
DRUGAPL-130277
Apomorphine Hydrochloride, Sublingual Thin Film
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female ≥18 years of age. 2. Clinical diagnosis of Idiopathic PD 3. Receiving stable doses of L-dopa +/- other adjunctive PD therapy for at least 4 weeks before study participation. 4. At least one OFF episode per day and a total daily OFF time of \> 2 hours duration. 5. Experience predictable OFF episodes in the morning on awakening prior to receiving morning dose of levodopa. 6. Stage I to III on the Hoehn and Yahr scale in the ON state. 7. If female and of childbearing potential, must agree to use one of the following methods of birth control: 8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study. 9. Able to understand the consent form, and to provide written informed consent.
Exclusion criteria
1. Atypical or secondary parkinsonism 2. Changes in L-dopa or other PD drug dosing regimens 4 weeks before the screening visit. 3. Past treatment with any form of apomorphine within 30 days of Dosing Day 1 (patients who stopped apomorphine for reasons other than lack of efficacy OR tolerability issues may be considered for the trial). 4. Female who is pregnant or lactating. 5. Contraindications to APOKYN or hypersensitive to apomorphine hydrochloride or any of the ingredients of APOKYN (notably sodium metabisulfite), or Tigan®. 6. Participation in any other clinical trial within 14 days of the screening visit. 7. Receipt of any investigational (i.e., unapproved) medication within 30 days of the screening visit. 8. Currently taking, or likely to need to take at any time during the course of the study 9. Currently taking dopamine antagonists or depleting drugs excluding anticholinergics and/or antihistamines with anticholinergic effects. 10. Drug or alcohol dependency in the past 6 months. 11. Clinically significant orthostatic hypotension. 12. Malignant melanoma or a history of previously treated malignant melanoma within 5 years. 13. Clinically significant medical surgical or laboratory abnormality in the judgment of the investigator. 14. Psychiatric disorder, including but not limited to dementia or any disorder that, in the opinion of the Investigator requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult. 15. Dementia that precludes providing informed consent. 16. Potential for lack of compliance and follow-up in the judgment of the investigator. 17. Any other condition, current therapy, or prior therapy (within 30 days of the screening visit), which, in the opinion of the Investigator, would make the subject unsuitable for the study. 18. Previous neurosurgery for PD. 19. Donation of blood or plasma in the 30 days prior to dosing. 20. Presence of cankers or mouth sores.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast) | Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5. | 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). |
| The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277 | At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5. | 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). |
| Time to 'ON' State From Time of Dosing of APL-130277 | At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5. | 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. |
| Duration of 'ON' Response From Time of Dosing of APL-130277 | At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5. | 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. |
| Percentage of Patients Who Completed the Trial and Experienced an 'ON' Episode | At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5. | 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. |
| Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax) | Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5. | 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). |
| PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax) | Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5. | 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. |
| PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast) | Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5. | 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. |
| PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90) | Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment | At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5. | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | APL-130277 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 61.5 years STANDARD_DEVIATION 8.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment United States | 19 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 13 / 19 |
| serious Total, serious adverse events | 1 / 19 |
Outcome results
Primary
Duration of 'ON' Response From Time of Dosing of APL-130277
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.
Time frame: 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'.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| APL-130277 | Duration of 'ON' Response From Time of Dosing of APL-130277 | 50.0 minutes | Standard Deviation 19.36 |
Primary
Percentage of Patients Who Completed the Trial and Experienced an 'ON' Episode
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| APL-130277 | Percentage of Patients Who Completed the Trial and Experienced an 'ON' Episode | 78.9 percentage of participants |
Primary
Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL-130277 | Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax) | 10 mg APL-130277 Dose 1 Day 1 | 2.01 ng/mL | Standard Deviation 0.914 |
| APL-130277 | Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax) | 15 mg APL-130277 Dose 2 Day 1 | 2.52 ng/mL | Standard Deviation 1.04 |
| APL-130277 | Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax) | 10 mg APL-130277 Dose 1 Day 2 | 4.18 ng/mL | — |
| APL-130277 | Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax) | 20 mg APL-130277 Dose 1 Day 2 | 3.82 ng/mL | Standard Deviation 1.81 |
| APL-130277 | Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax) | 25 mg APL-130277 Dose 2 Day 2 | 4.84 ng/mL | — |
| APL-130277 | Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax) | 20 mg APL-130277 Dose 1 Day 3 | 2.82 ng/mL | Standard Deviation 1.38 |
| APL-130277 | Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax) | 25 mg APL-130277 Dose 1 Day 3 | 12.3 ng/mL | — |
| APL-130277 | Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax) | 30 mg APL-130277 Dose 1 Day 3 | 4.22 ng/mL | — |
| APL-130277 | 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
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL-130277 | 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 | — |
| APL-130277 | 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 |
| APL-130277 | 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 |
| APL-130277 | 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 |
| APL-130277 | 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 | — |
| APL-130277 | 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 |
| APL-130277 | 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 | — |
| APL-130277 | 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 | — |
| APL-130277 | 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 | — |
Primary
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL-130277 | 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 |
| APL-130277 | 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 | — |
| APL-130277 | 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 |
| APL-130277 | 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 | — |
| APL-130277 | 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 |
| APL-130277 | 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 |
| APL-130277 | 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 | — |
| APL-130277 | 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 | — |
| APL-130277 | 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 |
Primary
PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| APL-130277 | PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax) | 10 mg APL-130277 Dose 1 Day 1 | 60.0 minutes |
| APL-130277 | PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax) | 15 mg APL-130277 Dose 2 Day 1 | 35.0 minutes |
| APL-130277 | PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax) | 20 mg APL-130277 Dose 1 Day 2 | 47.0 minutes |
| APL-130277 | PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax) | 20 mg APL-130277 Dose 1 Day 3 | 56.5 minutes |
| APL-130277 | PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax) | 25 mg APL-130277 Dose 2 Day 3 | 45.0 minutes |
Primary
PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL-130277 | PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast) | 10 mg APL-130277 Dose 1 Day 1 | 89.4 minutes | Standard Deviation 8.63 |
| APL-130277 | PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast) | 15 mg APL-130277 Dose 2 Day 1 | 90.8 minutes | Standard Deviation 2.04 |
| APL-130277 | PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast) | 10 mg APL-130277 Dose 1 Day 2 | 95.0 minutes | — |
| APL-130277 | PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast) | 20 mg APL-130277 Dose 1 Day 2 | 88.9 minutes | Standard Deviation 15.1 |
| APL-130277 | PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast) | 25 mg APL-130277 Dose 2 Day 2 | 94.0 minutes | — |
| APL-130277 | PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast) | 20 mg APL-130277 Dose 1 Day 3 | 95.2 minutes | Standard Deviation 6.4 |
| APL-130277 | PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast) | 25 mg APL-130277 Dose 1 Day 3 | 102 minutes | — |
| APL-130277 | PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast) | 30 mg APL-130277 Dose 1 Day 3 | 92.0 minutes | — |
| APL-130277 | 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
The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| APL-130277 | 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 |
| APL-130277 | 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 |
| APL-130277 | 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 |
| APL-130277 | 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 |
| APL-130277 | 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 |
| APL-130277 | 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 |
Primary
Time to 'ON' State From Time of Dosing of APL-130277
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.
Time frame: 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'.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| APL-130277 | Time to 'ON' State From Time of Dosing of APL-130277 | 24.0 minutes | Standard Deviation 7.61 |
Secondary
Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL-130277 | 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 |
| APL-130277 | 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 |
| APL-130277 | 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 |
| APL-130277 | 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 23.2 |
| APL-130277 | 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 |