A Phase 2 Study to Examine the Safety, Tolerability and Efficacy of APL-130277 in Patients With Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
研究概览
简要总结
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •Clinically significant orthostatic hypotension.
- •Malignant melanoma or a history of previously treated malignant melanoma within 5 years.
- •Clinically significant medical surgical or laboratory abnormality in the judgment of the investigator.
- •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.
- •Dementia that precludes providing informed consent.
- •Potential for lack of compliance and follow-up in the judgment of the investigator.
- •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.
- •Previous neurosurgery for PD.
- •Donation of blood or plasma in the 30 days prior to dosing.
- •Presence of cankers or mouth sores.
研究组 & 干预措施
APL-130277
open label baseline comparison
干预措施: APL-130277 (Drug)
结局指标
主要结局
The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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).
次要结局
- 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.)