Clinical trial NCT00335153: Levodopa-Carbidopa Intestinal Gel Open-Label Study in Advanced Parkinson's Disease
Official title: An Open-Label, 12-Month Safety and Efficacy Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Subjects With Advanced Parkinson's Disease and Severe Motor Fluctuations Despite Optimized Treatment With Available Parkinson's Disease Medications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced Parkinson's Disease
Keywords: severe motor fluctuations
levodopa
levodopa/carbidopa intestinal gel
efficacy
dyskinesia
Parkinson's Disease
carbidopa
DUOPA
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2006-06-09
Enrollment: 354
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study will be to provide further evidence of the long-term safety and tolerability of levodopa-carbidopa intestinal gel (Duodopa®) over 12-months in participants with advanced Parkinson's disease (PD) and severe motor fluctuations.

Detailed description: The study was composed of a screening period followed by 3 sequential on-treatment periods, as follows:

* Screening Period (up to 28 days): determination of eligibility and discontinuation of antiparkinsonian disease medications other than levodopa-carbidopa immediate release (LC-oral) prior to nasojejunal (NJ) tube placement.
* NJ Test Period (2 to 14 days): first hospitalization period, Baseline assessments, placement of NJ tube, and optimization of levodopa-carbidopa intestinal gel (LCIG) treatment via NJ tube and infusion pump (participant was hospitalized for NJ tube placement but hospitalization was not required for entire duration of LCIG treatment optimization).
* PEG-J Period (2 to 14 days): second hospitalization period; placement of PEG-J tube; further optimization of LCIG treatment.
* Post PEG-J Long-Term Treatment Period (Day 28 to Day 378): LCIG administration via a permanent PEG-J tube and infusion pump, with dosage adjusted according to clinical condition.

Eligibility criteria: Inclusion Criteria:

* Idiopathic Parkinson's disease (PD) according to United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria
* Levodopa-responsive with severe motor fluctuations
* Recognizable off and on state (motor fluctuations) confirmed by diary

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 (such as narrow angle glaucoma)

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs
timeFrame: Screening through Day 378 + 30 days
measure: Number of Participants With Device Complications During the Nasojejunal (NJ) Test Period
timeFrame: NJ Test Period (from 2 to 14 days)
measure: Number of Participants With Device Complications During the Percutaneous Endoscopic Gastrostomy - With Jejunal Extension Tube (PEG-J) Surgery and Post-PEG Long Term Treatment Periods
timeFrame: PEG-J Surgery Period (from 2 to 14 days) through the Long Term Treatment Period (Day 28 to Day 378)
measure: Number of Participants With Potentially Clinically Significant Values for Hematology Parameters
timeFrame: Screening through Day 378
measure: Number of Participants With Potentially Clinically Significant Values for Clinical Chemistry Parameters
timeFrame: Screening through Day 378
measure: Number of Participants With Potentially Clinically Significant Vital Sign Parameters
timeFrame: up to 56 weeks
measure: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters
timeFrame: Screening through Day 378
measure: Number of Participants With Sleep Attacks at Baseline
timeFrame: Baseline
measure: Number of Participants With Sleep Attacks During the Post-PEG Long-Term Treatment Period
timeFrame: During the Post-PEG Long-Term Treatment Period (Day 28 through Day 378)
measure: Summary of Minnesota Impulsive Disorder Interview (MIDI) Assessment of Intense Impulsive Behavior at Baseline (BL) and During the Post-PEG Long-term Treatment (PPLT) Period
timeFrame: Baseline, during the Post-PEG Long-term Treatment Period (Day 28 through Day 378)
measure: Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Endpoint
timeFrame: Baseline, Endpoint (last Post-PEG Long-Term Period visit up to Day 378)
measure: Number of Participants With Confirmed Cases of Melanoma
timeFrame: Screening up to Day 378
measure: Number of Participants Taking at Least 1 Concomitant Medication During the Study
timeFrame: Screening up to Day 378
Secondary outcomes:
measure: Change From Baseline in Average Daily "Off" Time at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Average Daily Normalized "On" Time With Troublesome Dyskinesia at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Average Daily "On" Time Without Troublesome Dyskinesia at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Clinical Global Impression - Status (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at Month 12
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Summary Index at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Mobility Domain Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Activities of Daily Living Domain Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Emotional Well-Being Domain Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Stigma Domain Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Social Support Domain Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Cognition Domain Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Communication Domain Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Bodily Discomfort Domain Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Summary Index at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Visual Analogue Scale (VAS) at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
measure: Change From Baseline in Zarit Burden Interview (ZBI) Total Score at Endpoint
timeFrame: Baseline, Endpoint (last post-baseline visit up to Day 378)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Site Reference ID/Investigator# 50065
state: Alabama
city: Fountain Valley
country: United States
facility: Site Reference ID/Investigator# 50059
state: California
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator# 50048
state: California
city: Oceanside
country: United States
facility: Site Reference ID/Investigator# 50076
state: California
city: Englewood
country: United States
facility: Site Reference ID/Investigator# 50061
state: Colorado
city: Washington
country: United States
facility: Site Reference ID/Investigator# 50079
state: District of Columbia
city: Bradenton
country: United States
facility: Site Reference ID/Investigator# 50077
state: Florida
city: Fort Lauderdale
country: United States
facility: Site Reference ID/Investigator# 50060
state: Florida
city: Gainesville
country: United States
facility: Site Reference ID/Investigator# 50049
state: Florida
city: Jacksonville
country: United States
facility: Site Reference ID/Investigator# 50047
state: Florida
city: Port Charlotte
country: United States
facility: Site Reference ID/Investigator# 50068
state: Florida
city: Tampa
country: United States
facility: Site Reference ID/Investigator# 50046
state: Florida
city: Augusta
country: United States
facility: Site Reference ID/Investigator# 50062
state: Georgia
city: Chicago
country: United States
facility: Site Reference ID/Investigator# 50050
state: Illinois
city: Chicago
country: United States
facility: Site Reference ID/Investigator# 50078
state: Illinois
city: Lexington
country: United States
facility: Site Reference ID/Investigator# 50064
state: Kentucky
city: Shreveport
country: United States
facility: Site Reference ID/Investigator# 50075
state: Louisiana
city: Baltimore
country: United States
facility: Site Reference ID/Investigator# 50080
state: Maryland
city: Baltimore
country: United States
facility: Site Reference ID/Investigator# 50074
state: Maryland
city: St. Louis
country: United States
facility: Site Reference ID/Investigator# 50073
state: Missouri
city: Omaha
country: United States
facility: Site Reference ID/Investigator# 50042
state: Nebraska
city: Manhasset
country: United States
facility: Site Reference ID/Investigator# 50072
state: New York
city: New York
country: United States
facility: Site Reference ID/Investigator# 50067
state: New York
city: New York
country: United States
facility: Site Reference ID/Investigator# 50066
state: New York
city: Raleigh
country: United States
facility: Site Reference ID/Investigator# 50069
state: North Carolina
city: Winston-Salem
country: United States
facility: Site Reference ID/Investigator# 50063
state: North Carolina
city: Cincinnati
country: United States
facility: Site Reference ID/Investigator# 50043
state: Ohio
city: Cleveland
country: United States
facility: Site Reference ID/Investigator# 50044
state: Ohio
city: Burlington
country: United States
facility: Site Reference ID/Investigator# 50058
state: Vermont
city: Kirkland
country: United States
facility: Site Reference ID/Investigator# 50045
state: Washington
city: Milwaukee
country: United States
facility: Site Reference ID/Investigator# 50070
state: Wisconsin
city: Adelaide
country: Australia
facility: Site Reference ID/Investigator# 46429
city: Heidelberg
country: Australia
facility: Site Reference ID/Investigator# 46427
city: Westmead
country: Australia
facility: Site Reference ID/Investigator# 46425
city: Edmonton
country: Canada
facility: Site Reference ID/Investigator# 54545
city: Montreal
country: Canada
facility: Site Reference ID/Investigator# 46433
city: Toronto
country: Canada
facility: Site Reference ID/Investigator# 46434
city: Brno
country: Czech Republic
facility: Site Reference ID/Investigator# 46436
city: Hradec Kralove
country: Czech Republic
facility: Site Reference ID/Investigator# 46438
city: Pardubice
country: Czech Republic
facility: Site Reference ID/Investigator# 46435
city: Prague 2
country: Czech Republic
facility: Site Reference ID/Investigator# 46437
city: Prague 5
country: Czech Republic
facility: Site Reference ID/Investigator# 46439
city: Lahti
country: Finland
facility: Site Reference ID/Investigator# 48003
city: Berlin
country: Germany
facility: Site Reference ID/Investigator# 48028
city: Berlin
country: Germany
facility: Site Reference ID/Investigator# 48029
city: Freiburg
country: Germany
facility: Site Reference ID/Investigator# 48036
city: Goettingen
country: Germany
facility: Site Reference ID/Investigator# 48034
city: Hanau
country: Germany
facility: Site Reference ID/Investigator# 48022
city: Hanover
country: Germany
facility: Site Reference ID/Investigator# 48024
city: Mainz
country: Germany
facility: Site Reference ID/Investigator# 48035
city: Tel Aviv
country: Israel
facility: Site Reference ID/Investigator# 49882
city: Arcugnano
country: Italy
facility: Site Reference ID/Investigator# 50131
city: Catania
country: Italy
facility: Site Reference ID/Investigator# 50132
city: Genoa
country: Italy
facility: Site Reference ID/Investigator# 50128
city: Lido di Camaiore
country: Italy
facility: Site Reference ID/Investigator# 50129
city: Naples
country: Italy
facility: Site Reference ID/Investigator# 50130
city: Rome
country: Italy
facility: Site Reference ID/Investigator# 50127
city: Nijmegen
country: Netherlands
facility: Site Reference ID/Investigator# 50138
city: Auckland
country: New Zealand
facility: Site Reference ID/Investigator# 50126
city: Christchurch
country: New Zealand
facility: Site Reference ID/Investigator# 50123
city: Hamilton
country: New Zealand
facility: Site Reference ID/Investigator# 50124
city: Wellington
country: New Zealand
facility: Site Reference ID/Investigator# 50125
city: Lodz
country: Poland
facility: Site Reference ID/Investigator# 50140
city: Poznan
country: Poland
facility: Site Reference ID/Investigator# 50139
city: Almada
country: Portugal
facility: Site Reference ID/Investigator# 50136
city: Coimbra
country: Portugal
facility: Site Reference ID/Investigator# 50134
city: Lisbon
country: Portugal
facility: Site Reference ID/Investigator# 50135
city: Porto
country: Portugal
facility: Site Reference ID/Investigator# 50137
city: Kazan
country: Russian Federation
facility: Site Reference ID/Investigator# 50143
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 50141
city: St. Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator# 50145
city: St. Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator# 50142
city: St. Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator# 50147
city: St. Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator# 50146
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 50154
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 50152
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 50202
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 50155
city: Madrid
country: Spain
facility: Site Reference ID/Investigator# 50153
city: Bangkok
country: Thailand
facility: Site Reference ID/Investigator# 50150
city: Bangkok
country: Thailand
facility: Site Reference ID/Investigator# 50151
city: Liverpool
country: United Kingdom
facility: Site Reference ID/Investigator# 50149
city: London
country: United Kingdom
facility: Site Reference ID/Investigator# 50148
Study officials:
affiliation: AbbVie
name: Janet Benesh
role: STUDY_DIRECTOR
References:
citation: Chang FC, Kwan V, van der Poorten D, Mahant N, Wolfe N, Ha AD, Griffith JM, Tsui D, Kim SD, Fung VS. Intraduodenal levodopa-carbidopa intestinal gel infusion improves both motor performance and quality of life in advanced Parkinson's disease. J Clin Neurosci. 2016 Mar;25:41-5. doi: 10.1016/j.jocn.2015.05.059. Epub 2016 Jan 14.
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: Fernandez HH, Standaert DG, Hauser RA, Lang AE, Fung VS, Klostermann F, Lew MF, Odin P, Steiger M, Yakupov EZ, Chouinard S, Suchowersky O, Dubow J, Hall CM, Chatamra K, Robieson WZ, Benesh JA, Espay AJ. Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results. Mov Disord. 2015 Apr;30(4):500-9. doi: 10.1002/mds.26123. Epub 2014 Dec 24.