Global REsponsE During iNFusIon of a gEl With LevoDopa/Carbidopa (GREENFIELD)

• ClinicalTrials.gov Identifier: NCT01754129
• Recruitment Status: Completed
• First Posted: December 21, 2012
• Results First Posted: August 10, 2018
• Last Update Posted: August 10, 2018
• Sponsor: AbbVie (prior sponsor, Abbott)
• Information provided by (Responsible Party): AbbVie ( AbbVie (prior sponsor, Abbott) )

Study Description

Brief Summary:

This multicenter, post marketing observational study (PMOS) was designed to evaluate the long-term effectiveness of levodopa/carbidopa intestinal gel (DUODOPA) on motor fluctuations (duration of OFF periods) in participants with advanced levodopa-responsive Parkinson's disease (PD) and severe motor fluctuations and hyper-/dyskinesia (involuntary movements). Secondary objectives of this study were to assess the participants' quality of life; to assess the long-term safety of DUODOPA; to assess disability, cognitive function, and non-professional caregiver burden; and to assess the economic and social impact of family caregiver assistance.

Condition or disease
Parkinson's Disease

Detailed Description:

Male or female participants ages 18 years of age who were already on DUODOPA treatment and had concluded the naso-intestinal phase were included in this study. DUODOPA was administered via a portable pump directly into the proximal small intestine via a percutaneous endoscopic transgastric jejunostomy (PEG-J) tube. There were 3 planned visits during the study: enrollment (Visit 1), 1 year (Visit 2), and 2 years (Visit 3).

Study Design

• Study Type: Observational
• Actual Enrollment: 148 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Global REsponsE During iNFusIon of a gEl With LevoDopa/Carbidopa (GREENFIELD)
• Study Start Date: December 2012
• Actual Primary Completion Date: May 2016
• Actual Study Completion Date: May 2016

Groups and Cohorts

Group/Cohort
Participants with Parkinson's disease; Participants with advanced levodopa-responsive Parkinson's disease and severe motor fluctuations and hyper-/dyskinesia who were prescribed and treated in accordance with the local levodopa/carbidopa intestinal gel product label

Outcome Measures

Primary Outcome Measures :

1. Unified Parkinson's Disease Rating Scale (UPDRS) IV (Complications of Therapy) Item 39 (Proportion of Waking Day Spent in "Off") Score: Mean Change From Baseline to the Last Available Follow up [ Time Frame: Baseline/Visit 1 and Visit 2 (Year 1) or Visit 3 (Year 2) ]
   Section B of the UPDRS IV questionnaire consists of 4 individual items that assess the degree of clinical fluctuations. Item 39 is the percentage of "off" times (when PD symptoms are not adequately controlled by the drug) during the waking day. The Item 39 score ranges from 0 (None), 1 (1- 25% of the waking day), 2 (26 - 50% of the waking day), 3 (51 - 75% of the waking day), and 4 (76 - 100% of the waking day). The mean change from baseline was calculated as the score at the last available follow up visit minus the score at baseline/Visit 1. Negative change from baseline for "off" time indicates improvement.

Secondary Outcome Measures :

1. Unified Parkinson's Disease Rating Scale (UPDRS) IV (Complications of Therapy) Part A+B Score: Mean Change From Baseline to Visits 2 and 3 [ Time Frame: Baseline/Visit 1, Visit 2 (Year 1), and Visit 3 (Year 2) ]
   The UPDRS is an Investigator-used rating tool to follow the course of Parkinson's disease. Scores for dyskinesias, early-morning dystonia, and clinical fluctuations ("off" times when PD symptoms are not adequately controlled by the drug) were assessed by the sum of the Part A+B items, questions 32-39. Questions 32-34 and 39 are measured on a 5-point scale (0-4), with 0 being no disease and 4 representing severe disease. Higher scores indicate a greater duration of dyskinesia (Q32), disability (Q33), and pain (Q34), and proportion of the waking day spent in "off" (Q39). Questions 35-38 are scored on a binary scale where 0= no and 1=yes, with higher scores indicating a higher incidence of early morning dystonia, and a higher degree of clinical fluctuations. The total score ranges from 0 (normal) to 20 (severe disease). Negative changes from baseline indicate improvement.
2. Change in Unified Parkinson's Disease Rating Scale on Mentation, Behavior and Mood (UPDRS I) and Activities of Daily Living (UPDRS II) During On and Off Phases [ Time Frame: Baseline/Visit 1, Visit 2 (Year 1), and Visit 3 (Year 2) ]
   The UPDRS is an Investigator-used rating tool to follow the course of Parkinson's disease. The Part I Score is the sum of the answers to the 4 questions that comprise Part I, each of which are measured on a 5-point scale (0-4). The Part I score ranges from 0 to 16 and higher scores are associated with more disability. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (0-4). The Part II score ranges from 0-52 and higher scores are associated with more disability. Scores for both "On" time (when PD symptoms are well-controlled by the drug) and "Off" time (when PD symptoms are not adequately controlled by the drug) are presented. Negative changes from baseline indicate improvement.
3. Change in Parkinson's Disease Quality of Life Questionnaire (PDQ-39) Scores [ Time Frame: Baseline/Visit 1, Visit 2 (Year 1), and Visit 3 (Year 2) ]
   The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in PD. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The total score is between 0 and 156, calculated as the total sum of the items, and higher scores are associated with more severe symptoms. Negative changes from baseline indicate improvement.
4. Change in Parkinson's Disease Sleep Scale Version 2 (PDSS-2) Scores [ Time Frame: Baseline/Visit 1, Visit 2 (Year 1), and Visit 3 (Year 2) ]
   The Parkinson's Disease Sleep Scale version 2 (PDSS-2) is a self-administered 15-item questionnaire addressing sleep and nocturnal disturbances in PD, including sleep quality, difficulty falling and staying asleep, restlessness, pain, or muscle cramps in legs or arms, dreams or hallucinations, getting up at night to pass urine, immobility at night, painful posturing in the morning, tremor on waking, sleepiness upon waking, and snoring or breathing difficulties. Scores on each item range from 0 (never) to 4 (very frequent). The PDSS-2 total score ranges from 0 (no disturbance) to 60 (maximum nocturnal disturbance). Negative changes from baseline indicate improvement.
5. Change in Gait and Falls Questionnaire (GFQ) Scores [ Time Frame: Baseline/Visit 1, Visit 2 (Year 1), and Visit 3 (Year 2) ]
   The Gait and Falls questionnaire (GFQ) is a self-administered 16-item questionnaire addressing gait in daily living, the frequency and severity of freezing of gait, the frequency of festinating gait and its relation to falls, and the frequency and severity of falls. Scores on each item range from 0 (no symptoms) to 4 (severe symptoms). The GFQ total score ranges from 0 (normal function) to 64 (severely impaired function). Negative changes from baseline indicate improvement.
6. Change in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) Scores [ Time Frame: Baseline/Visit 1, Visit 2 (Year 1), and Visit 3 (Year 2) ]
   The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale is a 28-item survey used to assess the frequency and severity of behaviors including gambling, sexual behavior, buying, eating, performing tasks or hobbies, repeating simple activities, and PD medication use. Scores on each item range from 0 (never) to 4 (very often). The QUIP-RS total score ranges from 0 (normal function) to 112 (severely impaired function). Negative changes from baseline indicate improvement.
7. Economic and Social Impact of Family-provided Healthcare [ Time Frame: Baseline/Visit 1, Visit 2 (Year 1), and Visit 3 (Year 2) ]
   Family caregivers were surveyed regarding the participant's need for home health care for Parkinson's Disease; the amount of time dedicated to care each week; the need of a family caregiver to reduce or change their normal work hours in order to provide care; the number of working days per month spent performing caregiver responsibilities; the number of hours of professional assistance per week needed; and the hourly costs of professional assistance incurred per week.
8. Change in Relative Stress Scale (RSS) Scores [ Time Frame: Baseline/Visit 1, Visit 2 (Year 1), and Visit 3 (Year 2) ]
   The Relative Stress Scale is a 15-item questionnaire completed by family caregivers to assess personal distress, life upset, and negative feelings regarding caring for a family member with PD. Scores on each item range from 1 (not at all) to 5 (to a high degree). The RSS total score ranges from 15 (low stress) to 75 (severe stress). Negative changes from baseline indicate improvement.
9. Concomitant Diseases and Medications [ Time Frame: Baseline/Visit 1, Visit 2 (Year 1), and Visit 3 (Year 2) ]
   Concomitant diseases were coded using the MedDRA dictionary (version 15.1). Concomitant diseases present in ≥ 5% of participants started before or at Visit 1 and stopped after Visit 1 or ongoing or started after Visit 1 are presented. Non-PD medications in ≥ 5% of participants maintained with a start date previous to the date of Visit 1 and a stop date after date of Visit 1 or ongoing are listed.
10. Change in Global Effectiveness on Motor Symptoms as Compared to Baseline [ Time Frame: Baseline/Visit 1, Visit 2 (Year 1), and Visit 3 (Year 2) ]
    Motor symptoms were rated by neurologists using three categories: improvement, no change, or worsening as compared to symptoms present at baseline.
11. Participant Self-assessment Scale of DUODOPA Therapy [ Time Frame: Baseline/Visit 1, Visit 2 (Year 1), and Visit 3 (Year 2) ]
    Participants were asked to rate DUODOPA therapy on a scale from 0 to 10 (0-2 worse, 3-5, unsatisfactory, 6-8 satisfactory, 9-10, very good).
12. DUODOPA Total Daily Infusion Dosage [ Time Frame: Baseline, Visit 1, Visit 2, (Year 1) and Visit 3 (Year 2) ]
    The total daily DUODOPA infusion dosage was documented at study visits starting at the baseline visit. One mL of DUODOPA contains 20 mg levodopa and 5 mg carbidopa monohydrate.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Adult participants already on DUODOPA treatment in accordance with the local DUODOPA product label (treatment of advanced levodopa-responsive Parkinson's disease with severe motor fluctuations and hyper/dyskinesia when available combinations of PD medicinal products have not given satisfactory results) and according to specific reimbursement criteria were offered the opportunity to enroll in this study.

Criteria

Inclusion Criteria:

• Participants already on treatment with DUODOPA (having already concluded the naso-intestinal treatment phase) according to the local DUODOPA product label and to routine clinical care for advanced PD patients
• Participants with available data on DUODOPA treatment, on previous PD conventional treatments and with at least one of the scales/questionnaires under study already collected on the participant's clinical chart
• Participant or legal representative has given written informed consent
• Non-professional caregiver (relative or familiar who give daily assistance to the patient) has given his/her written consent

Exclusion Criteria:

• History or presence of any condition that might interfere with the long-term continuation of the duodenal infusion of DUODOPA

Contacts and Locations

Sponsors and Collaborators

AbbVie (prior sponsor, Abbott)

Investigators

• Study Director: AbbVie Inc; AbbVie

More Information

• Responsible Party: AbbVie (prior sponsor, Abbott)
• ClinicalTrials.gov Identifier: NCT01754129
• Other Study ID Numbers: P13-895
• First Posted: December 21, 2012
• Results First Posted: August 10, 2018
• Last Update Posted: August 10, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by AbbVie ( AbbVie (prior sponsor, Abbott) ):

Caregiver; Quality of Life; Parkinson's Disease

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases