Interventional, Open-label, Exploratory Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Lu AE04621 and the Active Metabolite Lu AA40326 After Ascending Oral Doses of Lu AE04621 to Patients With Parkinson's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 4
- 主要终点
- Maximum Observed Concentration (Cmax) for Lu AE04621
研究概览
简要总结
To evaluate the safety, tolerability, pharmacokinetics, and efficacy of the Lu AE04621 and metabolite after ascending oral doses of Lu AE04621 in patients with Parkinson's Disease.
详细描述
The study comprised 5 cohorts (Cohorts 1 to 5), with each cohort consisting of 3 patients with Parkinson's disease (men and/or women). Each patient will be treated for 3 or 4 days, with increasing dose each day.
Dosing regimen will be decided at a dosing conferences. Dose levels can be increased, maintained or reduced both between cohorts but also within same cohort. The results are presented by dose level and reflect the actual doses administered.
A follow-up safety visit was scheduled approximately 7 days after the last dose of IMP.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient is diagnosed with idiopathic Parkinson Disease (consistent with the UK Parkinson's Disease Society Brain Bank Criteria for the Diagnosis of PD).
- •The patient's Hoehn and Yahr Staging score is ≤ 3 in the "ON" state.
- •The patient experiences motor fluctuations with at least 2.5 hours of "OFF" periods in the awake time and has predictable morning "OFF" episodes, which have been consistent within the past 4 weeks.
- •The patient currently has a good response to L-DOPA and has been receiving a stable dose of L-DOPA (≥3 doses per day of standard L-DOPA or ≥3 doses per day of Carbidopa and L-DOPA, Extended-Release Capsules) during at least four weeks prior to screening.
排除标准
- •The patient has cognitive impairment, defined as a Mini Mental State Examination(MMSE) score ≤ 26 at the Screening Visit.
- •The patient has severe disabling dyskinesia
- •The patient takes or has taken disallowed recent or concomitant medication (CYP2D6 inhibitors, CYP 3A4 substrate, Dopamine agonists, 5 HT3 antagonists, Anti-viral (Amantadine))
- •Other protocol defined inclusion and exclusion criteria may apply
研究组 & 干预措施
1.2 mg Lu AE04621
Patients having received a dose of 1.2 mg, independent of which Cohort they belong to.
干预措施: 1.2 mg Lu AE04621 (Drug)
0.04 mg Lu AE04621
Patients having received a dose of 0.04 mg, independent of which Cohort they belong to.
干预措施: 0.04 mg Lu AE04621 (Drug)
0.08 mg Lu AE04621
Patients having received a dose of 0.08 mg, independent of which Cohort they belong to.
干预措施: 0.08 mg Lu AE04621 (Drug)
0.2 mg Lu AE04621
Patients having received a dose of 0.2 mg, independent of which Cohort they belong to.
干预措施: 0.2 mg Lu AE04621 (Drug)
0.4 mg Lu AE04621
Patients having received a dose of 1.2 mg, independent of which Cohort they belong to.
干预措施: 0.4 mg Lu AE04621 (Drug)
0.6 mg Lu AE04621
Patients having received a dose of 0.6 mg, independent of which Cohort they belong to.
干预措施: 0.6 mg Lu AE04621 (Drug)
0.8 mg Lu AE04621
Patients having received a dose of 0.8 mg, independent of which Cohort they belong to.
干预措施: 0.8 mg Lu AE04621 (Drug)
1.0 mg Lu AE04621
Patients having received a dose of 1.0 mg, independent of which Cohort they belong to.
干预措施: 1.0 mg Lu AE04621 (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax) for Lu AE04621
时间窗: From dosing to up to 24 hours after dosing
Time to Onset of "ON" Time After Lu AE04621 Administration
时间窗: From dosing to 90 minutes after dosing
"ON" state is defined as a period of good control of parkinsonian features with relatively good overall function and mobility. Motor fluctuation assessments are patient-reported outcomes, and guidance will be given to the patients on how to complete them. Date and time will be registered when the patient turns to "ON" and "OFF" state. "OFF" state is defined as a period of poor control of parkinsonian features with relatively poor overall function, such as worsening tremor, rigidity, balance or bradykinesia. Data are no presented for the dose groups 0.04, 0.08, and 1.0 mg Lu AE04621 since no patients turned 'ON'.
Safety and Tolerability Based on the Safety Variables (Adverse Events, Clinical Safety Laboratory Tests, Vital Signs, Weight, and ECG)
时间窗: Baseline to day 11
Number of patients with an adverse event
Area Under the Plasma Concentration-time Curve (AUC(0-24 Hours)) for Lu AE04621
时间窗: From dosing to up to 24 hours after dosing
Apparent Elimination Half-life of Lu AE04621 in Plasma (t½)
时间窗: From dosing to up to 24 hours after dosing
Duration of "ON" Time
时间窗: From dosing up to 24h post-dose
"ON" state is defined as a period of good control of parkinsonian features with relatively good overall function and mobility. Motor fluctuation assessments are patient-reported outcomes, and guidance will be given to the patients on how to complete them. Date and time will be registered when the patient turns to "ON" and "OFF" state. "OFF" state is defined as a period of poor control of parkinsonian features with relatively poor overall function, such as worsening tremor, rigidity, balance or bradykinesia. Outcome measured in minutes. Data are no presented for the dose groups 0.04, 0.08, and 1.0 mg Lu AE04621 since no patients turned 'ON' following administration of Lu AE04621.
次要结局
未报告次要终点