A Phase 2 Study to Examine the Safety, Tolerability and Efficacy of APL-130277 in Patients With Parkinson's Disease
Overview
- Phase
- Phase 2
- Intervention
- APL-130277
- Conditions
- Parkinson's Disease
- Sponsor
- Sumitomo Pharma America, Inc.
- Enrollment
- 20
- Locations
- 4
- Primary Endpoint
- The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female ≥18 years of age.
- •Clinical diagnosis of Idiopathic PD
- •Receiving stable doses of L-dopa +/- other adjunctive PD therapy for at least 4 weeks before study participation.
- •At least one OFF episode per day and a total daily OFF time of \> 2 hours duration.
- •Experience predictable OFF episodes in the morning on awakening prior to receiving morning dose of levodopa.
- •Stage I to III on the Hoehn and Yahr scale in the "ON" state.
- •If female and of childbearing potential, must agree to use one of the following methods of birth control:
- •Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study.
- •Able to understand the consent form, and to provide written informed consent.
Exclusion Criteria
- •Atypical or secondary parkinsonism
- •Changes in L-dopa or other PD drug dosing regimens 4 weeks before the screening visit.
- •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).
- •Female who is pregnant or lactating.
- •Contraindications to APOKYN or hypersensitive to apomorphine hydrochloride or any of the ingredients of APOKYN (notably sodium metabisulfite), or Tigan®.
- •Participation in any other clinical trial within 14 days of the screening visit.
- •Receipt of any investigational (i.e., unapproved) medication within 30 days of the screening visit.
- •Currently taking, or likely to need to take at any time during the course of the study
- •Currently taking dopamine antagonists or depleting drugs excluding anticholinergics and/or antihistamines with anticholinergic effects.
- •Drug or alcohol dependency in the past 6 months.
Arms & Interventions
APL-130277
open label baseline comparison
Intervention: APL-130277
Outcomes
Primary Outcomes
The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
Time Frame: 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
Time Frame: 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.
Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
Time Frame: 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).
Duration of 'ON' Response From Time of Dosing of APL-130277
Time Frame: 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
Time Frame: 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.
PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
Time Frame: 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: Time of Maximum Observed Plasma Concentration (Tmax)
Time Frame: 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: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
Time Frame: 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.
PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
Time Frame: 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).
Secondary Outcomes
- 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.)