Clinical trial NCT00357994: Study of Efficacy, Safety and Tolerability of Levodopa-Carbidopa Intestinal Gel in Levodopa-Responsive Parkinson's Subjects
Official title: A Randomized, Double-Blind, Double-Dummy, Efficacy, Safety and Tolerability Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Parkinson's Subjects Receiving Optimized Treatments With Parkinson Medicinal Products Who Continue to Experience Persistent Motor Fluctuations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced Parkinson's Disease
Keywords: carbidopa
levodopa-carbidopa
levodopa
levodopa/carbidopa suspension
dyskinesia
Duodopa
levodopa-carbidopa intestinal gel
Severe Motor Fluctuations
DUOPA
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2006-07-28
Enrollment: 36
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study was to demonstrate the superiority of levodopa - carbidopa intestinal gel over treatment with optimized oral levodopa/carbidopa during 12 weeks.

Detailed description: Study S187.3.001 (NCT00357994) and Study S187.3.002 (NCT00660387) were 2 identically designed, Phase 3, 12-week, randomized, double-blind, double-dummy, parallel-group, multicenter studies recruiting subjects from distinct sites. These studies evaluated the efficacy, safety, and tolerability of levodopa-carbidopa intestinal gel (LCIG) in the treatment of levodopa-responsive subjects with advanced PD who had persistent severe motor fluctuations, despite optimized treatment with oral levodopa-carbidopa, concomitant with other available antiparkinsonian medications. Participants were randomized to either LCIG active gel + placebo capsules or levodopa-carbidopa immediate release (IR) active capsules + placebo gel. Both treatment arms received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration, active LCIG or placebo gel. Data from these 2 studies were combined for analysis. The decision to combine the study data for analysis was made before enrollment was completed for both studies.

Eligibility criteria: Inclusion Criteria:

* Idiopathic Parkinson's disease (PD) according to United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria
* Levodopa-responsive participants who demonstrate some identifiable 'on response,' established by Investigator observation
* Demonstrate severe motor fluctuations in spite of individually optimized treatment and where therapy options are indicated

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change From Baseline to Week 12 in Average Daily Normalized "Off" Time
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in Average Daily Normalized "On" Time Without Troublesome Dyskinesia at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Summary Index at Week 12
timeFrame: Baseline, Week 12
measure: Clinical Global Impression - Status (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in UPDRS Part III Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in EuroQual Quality of Life - 5 Dimensions (EQ-5D) Summary Index at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Zarit Burden Interview (ZBI) Total Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Average Daily Normalized "On" Time With Troublesome Dyskinesia at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Mobility Domain Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Activities of Daily Living Domain Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Emotional Well-Being Domain Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Stigma Domain Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Social Support Domain Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Cognition Domain Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Communication Domain Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Bodily Discomfort Domain Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Questions 32, 33, and 34 at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Visual Analogue Scale (VAS) at Week 12
timeFrame: Baseline, Week 12
measure: Employment Impairment (EMP) I Status at Baseline
timeFrame: Baseline
measure: Employment Impairment (EMP) II Status at Week 12
timeFrame: Week 12 (or early termination)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator# 45719
state: California
city: Englewood
country: United States
facility: Site Reference ID/Investigator# 45718
state: Colorado
city: Washington
country: United States
facility: Site Reference ID/Investigator# 45722
state: District of Columbia
city: Bradenton
country: United States
facility: Site Reference ID/Investigator# 45721
state: Florida
city: Gainesville
country: United States
facility: Site Reference ID/Investigator# 45705
state: Florida
city: Baltimore
country: United States
facility: Site Reference ID/Investigator# 45740
state: Maryland
city: St. Louis
country: United States
facility: Site Reference ID/Investigator# 45739
state: Missouri
city: Burlington
country: United States
facility: Site Reference ID/Investigator# 45703
state: Vermont
city: Bochum
country: Germany
facility: Site Reference ID/Investigator# 44970
city: Bremerhaven
country: Germany
facility: Site Reference ID/Investigator# 44971
city: Dresden
country: Germany
facility: Site Reference ID/Investigator# 44973
city: Hanover
country: Germany
facility: Site Reference ID/Investigator# 44965
city: Kiel
country: Germany
facility: Site Reference ID/Investigator# 44964
city: Marburg
country: Germany
facility: Site Reference ID/Investigator# 44966
city: Tuebingen
country: Germany
facility: Site Reference ID/Investigator# 44968
Study officials:
affiliation: AbbVie
name: Janet Benesh
role: STUDY_DIRECTOR
References:
citation: Shih TM, Sail KR, Jalundhwala YJ, Sullivan J, van Eijndhoven E, Zadikoff C, Marshall TS, Lakdawalla DN. The effect of functional status impairment on nursing home admission risk among patients with advanced Parkinson's disease. J Med Econ. 2020 Mar;23(3):297-307. doi: 10.1080/13696998.2019.1693383. Epub 2019 Nov 28.
citation: Lew MF, Slevin JT, Kruger R, Martinez Castrillo JC, Chatamra K, Dubow JS, Robieson WZ, Benesh JA, Fung VS. Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights from phase 3 clinical trials. Parkinsonism Relat Disord. 2015 Jul;21(7):742-8. doi: 10.1016/j.parkreldis.2015.04.022. Epub 2015 Apr 28.
citation: Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, Vanagunas A, Othman AA, Widnell KL, Robieson WZ, Pritchett Y, Chatamra K, Benesh J, Lenz RA, Antonini A; LCIG Horizon Study Group. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol. 2014 Feb;13(2):141-9. doi: 10.1016/S1474-4422(13)70293-X. Epub 2013 Dec 20.