A Study Comparing Efficacy of Levodopa-Carbidopa Intestinal Gel/Carbidopa-Levodopa Enteral Suspension and Optimized Medical Treatment on Dyskinesia in Subjects With Advanced Parkinson's Disease (DYSCOVER)

Parkinson's Disease (PD) Clinical Trial

— DYSCOVER  

Official title:

An Open-label, Randomized 12 Week Study Comparing Efficacy of Levodopa-Carbidopa Intestinal Gel/Carbidopa-Levodopa Enteral Suspension and Optimized Medical Treatment on Dyskinesia in Subjects With Advanced Parkinson's Disease DYSCOVER (DYSkinesia COmparative Interventional Trial on Duodopa VERsus Oral Medication)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02799381
• Other study ID #: M15-535
• Secondary ID: 2016-001403-23
• Status: Completed
• Phase: Phase 3
• Start date: February 9, 2017
• Est. completion date: September 19, 2019

Study information

• Verified date: August 2020
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to examine the effect of levodopa-carbidopa intestinal gel (LCIG) compared with optimized medical treatment (OMT) on dyskinesia in participants with advanced Parkinson's disease (PD).

Description:

This was a Phase 3b, open-label, randomized, multicenter, 12-week study. The study consisted of 3 sequential periods: Screening, Treatment, and Follow-Up. The OMT group had the same schedule of visits/procedures throughout the study as the LCIG treatment group, except for visits related to nasojejunal (NJ)/percutaneous endoscopic gastrostomy (PEG) procedures, titration of LCIG, and follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: September 19, 2019
• Est. primary completion date: September 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

• Participants must have a diagnosis of idiopathic Parkinson's disease (PD) according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria

• Participants with advanced levodopa-responsive PD and persistent motor fluctuations who have not been controlled with optimized medical treatment (OMT: the maximum therapeutic effect obtained with pharmacological antiparkinsonian therapies when no further improvement is expected with regard to any additional manipulations of levodopa and/or other antiparkinsonian medication based on the Investigator's clinical judgment)

• Unified Dyskinesia Rating Scale (UDysRs) Total score = 30 at Visit 3

Exclusion Criteria:

• Participant(s) treated with levodopa-carbidopa intestinal gel (LCIG) previously

• 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

• Participant(s) has undergone neurosurgery for the treatment of Parkinson's disease.

• Participant(s) has contraindications to levodopa (e.g. narrow angle glaucoma, malignant melanoma)

• 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

Related Conditions & MeSH terms

• Dyskinesias
• Parkinson Disease
• Parkinson's Disease (PD)

Intervention

Drug:
• Optimized antiparkinsonian treatment
Dose levels of prescribed antiparkinsonian medications were individually optimized to their maximum therapeutic effect.
• Levodopa-Carbidopa Intestinal Gel (LCIG)
Dose levels were individually optimized.

Device:
• CADD-Legacy ambulatory infusion pump
(manufactured by Smiths Medical)
• Percutaneous endoscopic gastrostomy tube
(PEG tube)
• Jejunal extension tube
(J-tube)

Locations

Country	Name	City	State
Finland	Helsinki Univ Central Hospital /ID# 151214	Helsinki
Finland	Oulun yliopistollinen sairaala /ID# 150947	Oulu
Greece	Mediterraneo Hospital /ID# 150955	Glyfada
Greece	University General Hospital of Heraklion "PA.G.N.I" /ID# 150956	Heraklion
Greece	University Hospital of Ioannin /ID# 150954	Ioannina
Hungary	Semmelweis Egyetem /ID# 170117	Budapest
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont I. sz. Belgyogyaszati Klinika /ID# 170116	Pécs	Pecs
Hungary	Szegedi Tudomanyegyetem /ID# 170115	Szeged
Italy	A.O. Univ. Ospedali Riuniti /ID# 150853	Ancona	Marche
Italy	Azienda USL Toscana Centro /ID# 150770	Florence
Italy	Seconda Universita' di Napoli /ID# 150851	Naples
Italy	Policlinico Tor Vergata /ID# 151167	Rome
Italy	Policlinico Universitario Campus Bio-Medico /ID# 150846	Rome	Lazio
Slovakia	Univerzitna Nemocnica Bratislava /ID# 150144	Bratislava
Slovakia	Univerzitna Nemocnica Bratislava /ID# 150171	Bratislava
Slovakia	Univerzitna nemocnica L. Pasteura /ID# 150146	Košice - Západ	Kosicky Kraj
Slovakia	Univerzitna nemocnica Martin /ID# 150145	Martin	Zilinsky Kraj
Spain	Hospital Universitario Cruces /ID# 203807	Barakaldo
Spain	Hospital General Univ de Elche /ID# 150154	Elche
Spain	Hospital General Universitario Gregorio Maranon /ID# 150155	Madrid
Spain	Hospital Univ de la Princesa /ID# 150157	Madrid
Spain	Hospital Univ Ramon y Cajal /ID# 150152	Madrid
Spain	Hospital Universitario Infanta /ID# 159696	Madrid
Spain	Hospital Regional Universitari /ID# 171485	Málaga	Malaga
Spain	Hospital Universitario Virgen Macarena /ID# 158861	Sevilla
Spain	Hospital Virgen de la Salud /ID# 166297	Toledo
United States	Parkinson's Disease Treatment Center of Southwest Florida /ID# 150095	Port Charlotte	Florida
United States	Central Texas Neurology Consul /ID# 150088	Round Rock	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Finland,  Greece,  Hungary,  Italy,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline to Week 12 in Unified Dyskinesia Rating Scale (UDysRS) Total Score	The Unified Dyskinesia Rating Scale (UDysRS) is a tool used to assess dyskinesia in Parkinson's disease (PD) and contains both self-evaluation questions and items that are assessed directly by the physician to objectively rate the abnormal movements associated with PD. Part 1 contains 11 questions about the ON time dyskinesia and the impact of ON-dyskinesia on experiences of daily living. Part 2 contains 4 questions about OFF-dystonia rating. Part 3 contains 7 questions about objective evaluation of dyskinesia impairment and Part 4 contains 4 questions regarding dyskinesia disability. Each question is scored with respect to severity, which is rated on a scale where 0 = normal, 1 = slight, 2 = mild, 3= moderate and 4 = severe. The UDysRS total score is obtained by summing the item scores, ranging from 0 to 104. Higher scores are associated with more disability. Negative changes from baseline indicate improvement.	Baseline, Week 12
Secondary	Mean Change From Baseline to Week 12 in ON Time Without Troublesome Dyskinesia	The Parkinson's Disease (PD) Symptom Diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected study visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e., 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. ON time is when PD symptoms are well controlled by the drug, and OFF time is when PD symptoms are not adequately controlled by the drug. Positive change from baseline for ON time without troublesome dyskinesia indicates improvement.	Baseline, Week 12
Secondary	Mean Change From Baseline to Week 12 in Parkinson's Disease Questionnaire-8 (PDQ-8) Summary Index	The Parkinson's Disease Questionnaire-8 (PDQ-8) is a disease-specific instrument designed to measure aspects of health that are relevant to participants with PD, and which may not be included in general health status questionnaires. The PDQ-8 is a self-administered questionnaire. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Higher scores are consistently associated with the more severe symptoms of the disease such as tremors and stiffness. The results are presented as a summary index. The PDQ-8 summary index ranges from 0 to 100, where lower scores indicate a better perceived health status. Negative changes from baseline indicate improvement.	Baseline, Week 12
Secondary	Mean Clinical Global Impression of Change (CGI-C) Score at Week 12	The Clinical Global Impression of Change (CGI-C) score is a clinician's rating scale for assessing Global Improvement of Change. The CGI-C rates improvement by 7 categories: very much improved (1), much improved (2), minimally improved (3), no change (4), minimally worse (5), much worse (6), very much worse (7). The CGI-C score ranges from 1 to 7, with lower scores indicating improvement.	Baseline, Week 12
Secondary	Mean Change From Baseline to Week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score (Activities of Daily Living)	The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part II score is the sum of the answers to the 13 questions related to Activities of Daily Living, and ranges from 0-52. Higher scores are associated with more disability. Negative values indicate improvement from baseline.	Baseline, Week 12
Secondary	Mean Change From Baseline to Week 12 in OFF Time	The Parkinson's Disease (PD) Symptom Diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected study visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e., 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. ON time is when PD symptoms are well controlled by the drug, and OFF time is when PD symptoms are not adequately controlled by the drug. Negative change from baseline for OFF time indicates improvement.	Baseline, Week 12
Secondary	Mean Change From Baseline to Week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score (Motor Examination)	The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part III score is the sum of the 27 answers related to Motor Examination, and ranges from 0-108. Higher scores are associated with more disability. Negative values indicate improvement from baseline.	Baseline, Week 12

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