An Open-Label, Two Part, Multicenter Study to Assess the Safety and Efficacy of Levodopa-Carbidopa Intestinal Gel (LCIG) for the Treatment of Non-Motor Symptoms in Subjects With Advanced Parkinson's Disease
Overview
- Phase
- Phase 3
- Intervention
- Levodopa-Carbidopa Intestinal Gel
- Conditions
- Advanced Parkinson's Disease
- Sponsor
- AbbVie (prior sponsor, Abbott)
- Enrollment
- 39
- Primary Endpoint
- Change From Baseline to Week 12 in the Non-Motor Symptom Scale (NMSS) Total Score
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The primary objective of this study is to evaluate change in non-motor symptoms from baseline to Week 12 as measured by the Non-Motor Symptom Scale total score.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject must have a diagnosis of idiopathic Parkinson's disease (PD) according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria
- •Demonstrate persistent motor fluctuations in spite of individually optimized treatment
- •Subject must experience a minimum of 3 hours "Off" time
Exclusion Criteria
- •Subject's PD diagnosis is unclear or there is a suspicion that the subject has a Parkinsonian syndrome such as secondary Parkinsonism (e.g., caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), Parkinson-plus syndrome (e.g., Multiple System Atrophy, Progressive Supranuclear Palsy, Diffuse Lewy Body Disease, Corticobasilar Degeneration), or other neurodegenerative disease that might mimic the symptoms of PD.
- •Subject has undergone neurosurgery for the treatment of Parkinson's disease
- •Subject for whom the placement of a PEG-J tube for LCIG treatment is contraindicated or is considered a high risk for the PEG-J procedure according to the gastroenterology evaluation (e.g., pathological changes of the gastric wall, inability to bring the gastric wall and abdominal wall together, blood coagulation disorders, peritonitis, acute pancreatitis, paralytic ileus).
Arms & Interventions
Levodopa-Carbidopa Intestinal Gel
Participants had the PEG-J tube placement procedure performed on Study Day 1 and, at the discretion of the investigator, began initiation and titration of LCIG infusion. Dosing was determined individually. The starting total daily dose of LCIG was based solely on the daily dose of the oral levodopa taken immediately prior to Study Day 1 and was adjusted to obtain the optimal clinical response for the individual participant. Participants received treatment for up to 60 weeks; participants who completed their Week 60 visit before LCIG was commercially available had the option to extend their LCIG therapy, if in the opinion of the investigator, the participant would benefit from continued LCIG treatment.
Intervention: Levodopa-Carbidopa Intestinal Gel
Levodopa-Carbidopa Intestinal Gel
Participants had the PEG-J tube placement procedure performed on Study Day 1 and, at the discretion of the investigator, began initiation and titration of LCIG infusion. Dosing was determined individually. The starting total daily dose of LCIG was based solely on the daily dose of the oral levodopa taken immediately prior to Study Day 1 and was adjusted to obtain the optimal clinical response for the individual participant. Participants received treatment for up to 60 weeks; participants who completed their Week 60 visit before LCIG was commercially available had the option to extend their LCIG therapy, if in the opinion of the investigator, the participant would benefit from continued LCIG treatment.
Intervention: Percutaneous Endoscopic Gastrostomy with Jejunal Extension (PEG-J)
Levodopa-Carbidopa Intestinal Gel
Participants had the PEG-J tube placement procedure performed on Study Day 1 and, at the discretion of the investigator, began initiation and titration of LCIG infusion. Dosing was determined individually. The starting total daily dose of LCIG was based solely on the daily dose of the oral levodopa taken immediately prior to Study Day 1 and was adjusted to obtain the optimal clinical response for the individual participant. Participants received treatment for up to 60 weeks; participants who completed their Week 60 visit before LCIG was commercially available had the option to extend their LCIG therapy, if in the opinion of the investigator, the participant would benefit from continued LCIG treatment.
Intervention: Levodopa-carbidopa Immediate Release (LC-IR) Tablets
Outcomes
Primary Outcomes
Change From Baseline to Week 12 in the Non-Motor Symptom Scale (NMSS) Total Score
Time Frame: Baseline and Week 12
The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; the total score is obtained by summing the item scores. The NMSS total score ranges from 0 to 360 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.
Secondary Outcomes
- Change From Baseline in NMSS Cardiovascular Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in NMSS Mood/Cognition Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in NMSS Perceptual Problems/Hallucinations Domain Score(Baseline and Week 12 and Week 60)
- Number of Participants Who Used Healthcare Resources Through Week 60(Week 60)
- Change From Baseline in NMSS Urinary Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in Mean Daily Normalized "On" Time Without Troublesome Dyskinesia Based on PD Diary(Baseline and Week 12 and Week 60)
- Change From Baseline for Unified Parkinson's Disease Rating Scale (UPDRS) Total Score(Baseline and Week 12 and Week 60)
- Change From Baseline in NMSS Attention/Memory Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in NMSS Gastrointestinal Tract Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline to Week 60 in the Non-Motor Symptom Scale (NMSS) Total Score(Baseline and Week 60)
- Change From Baseline in NMSS Sleep/Fatigue Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in NMSS Miscellaneous Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in Mean Daily Normalized "Off" Time Based on Parkinson's Disease Diary(Baseline and Week 12 and Week 60)
- Number of Participants Who Used Healthcare Resources During the First 4 Weeks(Weeks 1-4)
- Number of Participants With Adverse Events(Weeks 1-4 and Overall (from Week 1 through 30 days after the end of the LCIG Treatment Period; median duration of LCIG device exposure was 428 days))
- Change From Baseline in NMSS Sexual Function Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in UPDRS Part I: Mentation, Behavior, and Mood Score(Baseline and Week 12 and Week 60)
- Change From Baseline in UPDRS Part II: Activities of Daily Living (ADL) Score(Baseline and Week 12 and Week 60)
- Change From Baseline in UPDRS Part III: Motor Examination Score(Baseline and Week 12 and Week 60)
- Change From Baseline in UPDRS Part IV: Complications of Therapy Score(Baseline and Week 12 and Week 60)
- Change From Baseline in UPDRS Dyskinesia Items Score(Baseline and Week 12 and Week 60)
- Change From Baseline in PDQ-39 Mobility Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in PDQ-39 Activities of Daily Living Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in UPDRS Part V: Modified Hoehn and Yahr Staging Score(Baseline and Week 12 and Week 60)
- Change From Baseline in Parkinson's Disease Questionnaire-39 Item (PDQ-39) Summary Index(Baseline and Week 12 and Week 60)
- Change From Baseline in PDQ-39 Emotional Well-Being Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in PDQ-39 Stigma Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in PDQ-39 Social Support Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in PDQ-39 Cognition Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in PDQ-39 Communication Domain Score(Baseline and Week 12 and Week 60)
- Change From Baseline in PDQ-39 Bodily Discomfort Domain Score(Baseline and Week 12 and Week 60)
- Percentage of Participants With a Patient Global Impression of Change (PGIC) Response of Improved(Week 12 and Week 60)
- Treatment Satisfaction Questionnaire Scores(Week 12 and Week 60)
- Change From Baseline in Health-related Productivity(Baseline, Week 12 and Week 60)
- Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Working Memory Between Errors Score at Week 12(Baseline and Week 12)
- Change From Baseline in CANTAB Spatial Working Memory Strategy Score at Week 12(Baseline and Week 12)
- Change From Baseline in Controlled Oral Word Association Test (COWAT) Verbal Fluency Scores at Week 60(Baseline and Week 60)