An Open-Label, Single-Arm, Baseline-Controlled, Multicenter Study to Explore the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABT-SLV187 in Subjects With Advanced Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 8
- 主要终点
- Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period
研究概览
简要总结
To explore the safety, tolerability, pharmacokinetics and efficacy of ABT-SLV187 in advanced Parkinson's disease (PD) patients with severe motor complications. The complications of medical devices for the naso-jejunum (NJ) infusion system of ABT-SLV187 will also be investigated.
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
- 30 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Idiopathic PD according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank criteria
- •PD stage corresponds to 4 or 5 in the 'off' state according to the modified Hoehn & Yahr (H & Y) classification of disease severity
- •Levodopa-responsive subjects demonstrate some identifiable 'ON response' established by observation by Investigator and demonstrate severe motor fluctuations in spite of individually optimized treatment and where therapy options are indicated
排除标准
- •Diagnosis is unclear or a suspicion of other parkinsonian syndromes exists such as secondary parkinsonism
- •Undergone surgery for the treatment of PD
- •Contraindications to levodopa
- •Subjects with any neurological deficit that may interfere with the study assessments
研究组 & 干预措施
Levodopa-carbidopa intestinal gel
Following a 28-day Run-in Period where participants are switched from prior anti-PD medications to monotherapy with an oral 100 mg levodopa/10 mg carbidopa tablet (optimized every 3rd hour during waking hours), participants receive ABT-SLV187 (levodopa-carbidopa intestinal gel), administered over 16 hours a day with an infusion pump directly into the proximal jejunum by an NJ tube, for 3 weeks.
The individually-adjusted infusion dose (composed of the morning dose, the continuous maintenance dose, and the extra dose) is optimized by the Investigator for each participant during the study based on the participant's symptoms.
干预措施: ABT-SLV187 (Drug)
Levodopa-carbidopa intestinal gel
Following a 28-day Run-in Period where participants are switched from prior anti-PD medications to monotherapy with an oral 100 mg levodopa/10 mg carbidopa tablet (optimized every 3rd hour during waking hours), participants receive ABT-SLV187 (levodopa-carbidopa intestinal gel), administered over 16 hours a day with an infusion pump directly into the proximal jejunum by an NJ tube, for 3 weeks.
The individually-adjusted infusion dose (composed of the morning dose, the continuous maintenance dose, and the extra dose) is optimized by the Investigator for each participant during the study based on the participant's symptoms.
干预措施: Oral Levodopa/Carbidopa (Drug)
结局指标
主要结局
Number of Participants With Potentially Clinically Significant (PCS) Hematology Results During the ABT-SLV187 Treatment Period
时间窗: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
M=male, F=female, MCV=mean corpuscular volume, MCH=mean corpuscular hemoglobin, MCHC=mean corpuscular hemoglobin concentration.
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation During the Run-in Period
时间窗: During the Run-in period (up to approximately 28 days)
AE: any untoward medical occurrence in a participant that does not necessarily have a causal relationship with this treatment. SAE: an event that results in the death of a subject, is life threatening, results in hospitalization or prolongation of hospitalization, is a congenital anomaly, results in persistent or significant disability/incapacity, or other important medical event. Severity was rated as mild, moderate, or severe. AEs of special interest included: device-associated gastrointestinal disorders; cardiovascular fatalities; aspiration including aspiration pneumonia; a diagnosis of peripheral polyneuropathy (axonal, demyelinating or mixed type); possible symptoms of peripheral polyneuropathy; clinically significant weight loss. 'AEs at least possibly related' are defined as those that were assessed by investigator as probably related or possibly related.
Number of Participants With Potentially Clinically Significant (PCS) Vital Signs Results During the ABT-SLV187 Treatment Period
时间窗: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
↓=decrease, ↑=increase, BL=baseline, temp.=temperature, SBP=systolic blood pressure, Sup.=supine, Sta.=standing, DBP=diastolic blood pressure.
Number of Participants With PCS Values in Special Laboratory Parameters During the ABT-SLV187 Treatment Period
时间窗: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
M=male, F=female
Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation During the ABT-SLV187 Treatment Period
时间窗: From NJ placement to end of ABT-SLV187 Treatment Period (Day 21) +30 days
AE: any untoward medical occurrence in a participant that does not necessarily have a causal relationship with this treatment. SAE: an event that results in the death of a subject, is life threatening, results in hospitalization or prolongation of hospitalization, is a congenital anomaly, results in persistent or significant disability/incapacity, or other important medical event. Severity was rated as mild, moderate, or severe. AEs of special interest included: device-associated gastrointestinal disorders; cardiovascular fatalities; aspiration including aspiration pneumonia; a diagnosis of peripheral polyneuropathy (axonal, demyelinating or mixed type); possible symptoms of peripheral polyneuropathy; clinically significant weight loss. 'AEs at least possibly related' are defined as those that were assessed by investigator as probably related or possibly related.
Number of Participants With Potentially Clinically Significant Urinalysis Results During the ABT-SLV187 Treatment Period
时间窗: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Number of Participants With Potentially Clinically Significant 12-lead Electrocardiogram (ECG) Results During the ABT-SLV187 Treatment Period
时间窗: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
High potentially clinically significant Bazett's heart rate-corrected QT interval (QTcB) values were: 450 msec for males / 470 msec for females.
Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the "Normal" State on the Treatment Response Scale (TRS) I
时间窗: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
Participants were video recorded a total of 10 times for 1 to 2 minutes every 60 minutes while performing a standardized sequence of motor tasks: rest, finger taps, rapid alternating movement of hands, arising from chair and gait, including confirmation of postural stability. Based on these video recordings, a Video Evaluation Committee consisting of 3 neurologists individually evaluated the following Video Assessment and Treatment Response Scale (TRS) under blinded conditions: Finger Taps, Rapid Alternating Movement of Hands, Arising from Chair, Gait, Body Bradykinesia and Hypokinesia, Dyskinesia. The average of the neurologists' evaluations was calculated as a percentage of ratings in the "Normal" state (ie, "mild OFF" to "ON with mild dyskinesia") on the TRS I (total 10 assessments per day).
Number of Participants With PCS Blood Biochemistry Results During the ABT-SLV187 Treatment Period
时间窗: Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21)
M=male, F=female, γ-GTP=gamma-glutamyl transpeptidase.
次要结局
- Change From Baseline to the End of Treatment in Parkinson's Disease Diary Assessment(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- Schwab and England Activities of Daily Living Scale at Baseline and End of Treatment(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- Time to Reach Peak Plasma Concentration (Tmax) After Administration of Oral Levodopa/Carbidopa (L/C) Tablets and Intra-jejunal Administration of ABT-SLV187(Baseline (Day -1): pre-dose; 15, 30, 45, 60 mins post-morning dose; every 30 mins thereafter for 12 hrs. Day 21: pre-dose; 15, 30, 45, 60 mins post-infusion; every 30 mins from hrs 1 to 12 post-infusion; every 2 hrs from 12 to 16 hrs post-infusion.)
- Ratio of Metabolite 3-OMD to Levodopa (M/P [AUC0-12]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- Clinical Global Impression - Severity (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Baseline and End of Treatment(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- Mean Change From Baseline to the End of Treatment in Percentage of Ratings in the "OFF" and "Dyskinesia" States on the TRS I and the "Normal," "OFF," and "Dyskinesia" States on the TRS II(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- Modified Hoehn and Yahr Staging at Baseline and End of Treatment(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- Number of Participants With Product Quality Complaints (PQC) During the ABT-SLV187 Treatment Period(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- Baseline and Endpoint (End of Treatment) Video Scoring of Unified Parkinson's Disease Rating Scale (UPDRS) Items and Dyskinesia(Baseline (Day -1), Endpoint (Day 21))
- Change From Baseline to the End of Treatment in the Japanese Version of Parkinson's Disease Questionnaire 39 (PDQ-39) Total Score and Domain Scores(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- Degree of Fluctuation (2-12 Hours) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- Mean Change From Baseline to the End of Treatment in UPDRS Total Scores and Subscores(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), Trough Plasma Concentration (Cmin), and Cmin Within 2 and 12 Hours (Cmin [2-12 Hours]) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- The Area Under the Concentrations-time Curve From 0 to 12 and 0 to 16 Hours (AUC0-12, AUC0-16) After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))
- AUC0-12/Dose0-12, AUC0-16/Dose0-16 After Administration of Oral L/C Tablets and Intra-jejunal Administration of ABT-SLV187(Baseline (Day -1), End of ABT-SLV187 Treatment Period (Day 21))