Clinical trial NCT02549092: A Study to Examine the Effect of Levodopa-Carbidopa Intestinal Gel (LCIG) Therapy Relative to That of Optimized Medical Treatment (OMT) on Non-motor Symptoms (NMS) Associated With Advanced Parkinson's Disease (PD)
Official title: An Open-label, Randomized 26-Week Study Comparing Levodopa-Carbidopa INteStInal Gel (LCIG) THerapy to Optimized Medical Treatment (OMT) on Non-Motor Symptoms (NMS) in Subjects With Advanced Parkinson's Disease - INSIGHTS Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced Parkinson's Disease
Keywords: levodopa-carbidopa intestinal gel
levodopa
carbidopa
Advanced Parkinson's Disease
Non-Motor Symptom Scale NMSS
Parkinson's Disease Sleep Scale PDSS-2
efficacy
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2015-09-15
Enrollment: 89
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 is to examine the effect of LCIG relative to that of OMT on NMS associated with PD.

Detailed description: The study will consist of 3 sequential parts:

Part 1: Screening period. The screening period will consist of 3 visits, Visit 1 (V1), Visit 2 (\[V2\] \[optional\]) and the Randomization Visit (V3) in which the participant will be assessed to determine eligibility. The duration of the Screening Period can be between 30 to 67 days to accommodate the required procedures, training and collection of diaries, and to allow for stabilization of anti-PD medications and medications to treat NMS. All anti-PD medications and medications to treat NMS are required to be stable for a minimum of 30 days prior to randomization.

Part 2: Treatment period. Those participants randomized to OMT at the end of V3 will remain on their current optimized regimen. The day after randomization will be considered Day 1 of their treatment period and participants will have study visits at the end of Weeks 2, 6, 12, and 26. All participants randomized to the LCIG group should have all anti-PD medications, with the exception of levodopa formulations, tapered off within 14 days after randomization. Optional nasojujunal (NJ) and/or percutaneous endoscopic gastrostomy with a jejunal tube (PEG-J) placement will then occur. After that, the participant may begin initiation and titration of LCIG infusion to be adjusted to obtain the optimal clinical response. The day of initial NJ or PEG-J placement will be considered Day 1 for participants in the LCIG group. Study visits happen at the end of Weeks 2, 6, 12, and 26.

Part 3: Extension/Transition Period. Eligible participants who complete the 26 week study may continue into the Extension Period of the study. Participants in the LCIG arm will have study drug dispensation every 4 weeks and will have study visits every 6 months. Participants from the OMT arm will undergo the NJ (optional) and PEG-J procedures, titration, plus have visits at 2 weeks, 6 weeks, 3 months and 6 months post NJ or PEG-J. Participants will then continue to receive study drug every 4 weeks and will have study visits every 6 months until Duodopa is commercially available. Transition to a Post-Trial Access protocol will be possible if Duodopa does not become commercially available in a location.

Eligibility criteria: Inclusion Criteria:

1. Participant(s) must have a diagnosis of idiopathic Parkinson's disease according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria.
2. Participant(s) demonstrates persistent motor fluctuations in spite of individually optimized treatment.
3. The participant's Parkinson's disease is levodopa-responsive.
4. Participant(s) has had optimized treatment with available anti-PD medication and their motor symptoms are judged inadequately controlled on this optimized treatment. Optimized treatment is defined as the maximum therapeutic effect obtained with pharmacological antiparkinsonian therapies when no further improvement is expected regardless of any additional manipulations of levodopa and/or other antiparkinsonian medication. This will be based on the Investigator's clinical judgment.
5. Male or female participant(s) must be at least 30 years of age.
6. Minimum Parkinson's Disease Sleep Scale 2 (PDSS-2) total score of 18 at Baseline assessment.

Exclusion Criteria:

1. Participant'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) or other neurodegenerative disease that might mimic the symptoms of PD.
2. Participant(s) has undergone neurosurgery for the treatment of Parkinson's disease.
3. Known hypersensitivity to levodopa, carbidopa or radiopaque material.
4. Participant(s) has contraindications to levodopa (e.g. narrow angle glaucoma, malignant melanoma).
5. Participant(s) experiencing clinically significant sleep attacks or clinically significant impulsive behavior (e.g. pathological gambling, hypersexuality) at any point during the three months prior to the Screening evaluation as judged by the Principal Investigator.

Primary outcomes:
measure: Change From Baseline to Week 26 in the NMSS Total Score
timeFrame: Baseline, Week 26
measure: Change From Baseline to Week 26 in the Modified PDSS-2 Total Score
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Change From Baseline to Week 26 in Parkinson's Disease Questionnaire (PDQ-8) Summary Index Score
timeFrame: Baseline, Week 26
measure: Clinical Global Impression of Change (CGI-C) Final Score
timeFrame: End of Treatment Period (up to Week 26)
measure: Change From Baseline at Week 26 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score
timeFrame: Baseline, Week 26
measure: Change From Baseline to Week 26 in the NMSS Domain Scores
timeFrame: Baseline, Week 26
measure: Change From Baseline to Week 26 in the Modified PDSS-2 Domain Scores
timeFrame: Baseline, Week 26
measure: Change From Baseline at Week 26 in UPDRS Parts I, III, and IV Score
timeFrame: Baseline, Week 26
measure: Change From Baseline at Week 26 in Parkinson's Anxiety Scale (PAS) Total Score
timeFrame: Baseline, Week 26
measure: Change From Baseline at Week 26 in Geriatric Depression Scale (GDS-15) Score
timeFrame: Baseline, Week 26
measure: Change From Baseline at Week 26 in King's PD Pain Scale (KPPS) Score
timeFrame: Baseline, Week 26
measure: Patient Global Impression of Change (PGIC) Final Score
timeFrame: End of Treatment Period (up to Week 26)
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: Parkinson's and Movement /ID# 161596
state: California
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital /ID# 200056
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Neurolog /ID# 168699
state: Florida
city: Port Charlotte
country: United States
facility: Parkinson's Disease Treatment Center of Southwest Florida /ID# 168085
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center /ID# 168088
state: Illinois
city: Kansas City
country: United States
facility: St. Luke's Health System /ID# 168706
state: Missouri
city: Round Rock
country: United States
facility: Central Texas Neurology Consul /ID# 168087
state: Texas
city: Spokane
country: United States
facility: Inland Northwest Research /ID# 200113
state: Washington
city: Westmead
country: Australia
facility: Westmead Hospital /ID# 136575
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital /ID# 136577
state: South Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital /ID# 136780
state: Victoria
city: Shepparton
country: Australia
facility: Goulburn Valley Hospital /ID# 164202
state: Victoria
city: Edmonton
country: Canada
facility: University of Alberta /ID# 136586
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital /ID# 139341
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital /ID# 136585
state: Ontario
city: Bremerhaven
country: Germany
facility: Central Hospital Bremerhaven /ID# 136573
city: Athens
country: Greece
facility: 251 Airforce General Hospital /ID# 160594
state: Attiki
city: Glyfada
country: Greece
facility: Mediterraneo Hospital /ID# 208042
city: Ancona
country: Italy
facility: A.O. Univ. Ospedali Riuniti /ID# 135964
state: Marche
city: Bologna
country: Italy
facility: Ospedale Bellaria.Azienda USL IRCCS.Istituto delle Scienze Neurologiche di Bolog /ID# 136789
city: Foggia
country: Italy
facility: A.O.U. Ospedali Riuniti di Fog /ID# 136792
city: Messina
country: Italy
facility: A.O.U. Policlinico G. Martino /ID# 136790
city: Perugia
country: Italy
facility: Ospedale S.Maria della Miseri /ID# 160609
city: Ponderano,biella
country: Italy
facility: Azienda Sanitaria Locale di /ID# 160608
city: Roma
country: Italy
facility: Azienda Policlinico Umberto I /ID# 201223
city: Seoul
country: Korea, Republic of
facility: Severance Hospital /ID# 163019
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 162990
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 163018
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge /ID# 136579
state: Barcelona
city: Las Palmas de Gran Canaria
country: Spain
facility: CHU Insular-Materno Infantil /ID# 136783
state: Las Palmas
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona /ID# 137689
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau /ID# 136581
city: Cadiz
country: Spain
facility: Hospital Puerta del Mar /ID# 157977
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves /ID# 136583
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal /ID# 136784
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 145624
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe /ID# 136722
city: Solna
country: Sweden
facility: Karolinska Univ Sjukhuset /ID# 135961
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: