NCT03541356已完成2 期
A Phase IIa, Randomized, Double Blind, Placebo Controlled, Single Ascending Dose, Safety and Pharmacokinetic/Pharmacodynamic Study of INP103 (POD L-dopa) Administered in the Presence of DCI to L-dopa Responsive Parkinson's Disease Patients
Impel Pharmaceuticals7 个研究点 分布在 1 个国家目标入组 32 人开始时间: 2018年5月8日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 7
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events
研究概览
简要总结
A Phase IIa, Randomized, Double Blind, Placebo Controlled, Single Dose, Safety and Pharmacokinetic/Pharmacodynamic Study of INP103 (POD L-dopa) Administered in the Presence of Decarboxylase Inhibitor to L-dopa Responsive Parkinson's Disease Patients
详细描述
This is a Phase IIa randomized, double-blind, placebo-controlled, single dose study to compare the safety, tolerability and PK/PDyn of intranasal L-dopa following administration of INP103 in the presence of L-dopa decarboxylase inhibitor (DCI) during an OFF episode.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blind
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult males and females, 40 to 80 years of age (inclusive) at the time of Screening (Visit1)
- •Diagnosed with Idiopathic PD (by UK Brain Bank Criteria) with Modified Hoehn & Yahr (H&Y) Stage I-III during an ON period at Visit 1
- •Subjects who are prone to (and recognize) OFF episodes (when their usual PD medication has worn off)
- •Shown to be responsive to L-dopa medication (≥ 30% improvement in MDS-UPDRS Part III Motor Examination score) as assessed during the Screening period (Visit 2)
- •On a stable dose of L-dopa containing medication for at least 2 weeks prior to Visit 1 (up to 1200 mg/day) with no single dose exceeding 250 mg. All other anti-PD medication (e.g. dopamine agonists [DAs], monoamine oxidase-B inhibitor (MAOB-I) or catechol-O-methyl transferase (COMT) inhibitors ARE allowed if the subject has been on a stable dose for at least 30 days prior to Visit
- •Willing to omit their (usual) PD drugs (e.g. usual regular anti-PD medication including any L-dopa containing medication, DAs and/or COMT inhibitors and any required anti-OFF treatment) from 22:00 pm the evening prior to study dosing until 120 minutes post study treatment dosing.
- •Cohorts 1, 2 and 3 ONLY WILL take oral benserazide 25 mg on arrival at the research site (at 60 ± 5 minutes before dosing with INP103 or placebo).
- •Cohort 4 will omit oral benserazide and subjects may be dosed once OFF episode has been confirmed and all baseline assessments have been completed.
- •If female and of childbearing potential must agree to use adequate contraception (see Section 4.4) during the study
- •Able and willing to attend the necessary visits at the study centre
- •Willing to provide voluntary written informed consent signed prior to entry into the study
排除标准
- •Severe dyskinesia (defined as per MDS-UPDRS) during a 'normal day' that would significantly interfere with the subject's ability to perform study assessments
- •In receipt of L-dopa containing medication at > 1200 mg/day
- •History of significant psychotic episode(s) within the previous 12 months in the opinion of the Investigator, or currently receiving anti-psychotic medication at a moderate dose (quetiapine >50 mg/day, risperidone >1 mg/day or olanzapine >2.5 mg/day)
- •Mini Mental State Examination (MMSE) ≤ 25 as documented within the previous 36 months or as assessed by Investigator during Screening
- •History of suicidal ideation or attempted suicide within previous 12 months
- •Narrow-angle glaucoma
- •Presence of skin lesions that, in the opinion of the Investigator, may be cancerous
- •Females who are pregnant, planning a pregnancy or lactating
- •Subjects with any underlying physical condition that, in the opinion of the Investigator, would make it unlikely that the subject will comply with or be able to complete the study requirements
- •Use of any medication likely to interact with benserazide, carbidopa or INP103 (see Appendix 5)
- •Laboratory test abnormalities at Screening (Visit 1) deemed clinically significant by the Investigator.
- •History or presence of alcoholism or drug abuse within the 2 years prior to INP103 or placebo dosing
- •Administration of an investigational product in another trial within 30 days or 5 half-lives (whichever is longer) prior to INP103 or placebo dosing
- •Significant nasal congestion, physical blockage in either nostril, or significantly deviated nasal septum as evaluated by the PI or other suitably trained healthcare professional
- •Subjects who have previously shown hypersensitivity to L-dopa or benserazide (for Cohorts 1, 2 and 3), or L-dopa or carbidopa (for Cohort 4) or any of their excipients
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events
时间窗: 7 days
Assessment of treatment emergent adverse events after single dosing with INP103 (L-dopa or L-dopa/carbidopa)
次要结局
- Tmax of L-dopa(For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.)
- Mean Change From Baseline in MDS-UPDRS Score Over 2 Hours for C1, C2, C3 and Change From Baseline at 30, 60, 90, 120 Minutes for C4, in MDS-UPDRS Part III Score(For L-dopa 35 mg, 70 mg, 140 mg, assessment occurred at pre-dose, 15, 30, 45, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, assessment occurred at pre-dose, 30, 60, 90 and 120 minutes post-dose.)
- Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)(2 hours)
- Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)(From time = 0 to 2 hours post-dose)
- AUC0-2hr for L-dopa(For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 min)
- Mean Maximum Change From Baseline in MDS-UPDRS Part III Score(From time = 0 to 2 hours post-dose)
- Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline.(2 hours)
- Cmax of L-dopa(For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.)
- Subjective Time to "ON" as Evaluated by the Investigator(4 hours)
- Assessment of Time to "ON" as Evaluated by Subject Self-assessment(4 hours)
- AUC0-2h for Carbidopa(Plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose and AUC calculated from these from time 0 to 120 minutes.)
- Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores(For L-dopa 35 mg, 70 mg, 140 mg, assessments were made at pre-dose, 15, 30, 45, 60, 90, 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, assessments were made at pre-dose, 50, 60, 90, 120 minutes post-dose.)
- Cmax of Carbidopa(For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.)
- Tmax of Carbidopa(For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.)
研究者
研究点 (7)
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