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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00660387




Registration number
NCT00660387
Ethics application status
Date submitted
15/04/2008
Date registered
15/04/2008
Date last updated
12/01/2015

Titles & IDs
Public title
Study of Efficacy, Safety and Tolerability of Levodopa-Carbidopa Intestinal Gel in Levodopa-Responsive Parkinson's Subjects
Scientific 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
Secondary ID [1] 0 0
2007-003814-32
Secondary ID [2] 0 0
S187.3.002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Parkinson's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Levodopa carbidopa intestinal gel (LCIG)
Treatment: Drugs - Placebo Gel
Treatment: Drugs - Levodopa-carbidopa (LC) oral encapsulated immediate release (IR) tablets
Treatment: Drugs - Placebo (PBO) oral capsules
Treatment: Devices - CADD-Legacy® 1400 ambulatory infusion pump
Treatment: Devices - PEG tube
Treatment: Devices - J-tube

Experimental: Levodopa-Carbidopa Intestinal Gel (LCIG) + Placebo Capsules - Participants were randomized to LCIG (levodopa, 20 mg/mL and carbidopa monohydrate, 5 mg/mL) and placebo capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of LCIG.

Active Comparator: Placebo Gel + Levodopa-Carbidopa Capsules - Participants were randomized to placebo intestinal gel and oral levodopa-carbidopa (levodopa, 100 mg and carbidopa, 25 mg) Immediate Release (IR) capsules. Participants received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration of placebo.


Treatment: Drugs: Levodopa carbidopa intestinal gel (LCIG)
infusion should be kept within a range of 0.5-10 mL/hour (10-200 mg levodopa/hour) and is usually 2-6 mL/hour (40-120 mg levodopa/hour)

Treatment: Drugs: Placebo Gel


Treatment: Drugs: Levodopa-carbidopa (LC) oral encapsulated immediate release (IR) tablets


Treatment: Drugs: Placebo (PBO) oral capsules


Treatment: Devices: CADD-Legacy® 1400 ambulatory infusion pump


Treatment: Devices: PEG tube
percutaneous endoscopic gastrostomy tube

Treatment: Devices: J-tube
jejunal tube

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Week 12 in Average Daily Normalized "Off" Time - Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Negative change from baseline for "off" time indicates improvement.
Timepoint [1] 0 0
Baseline, Week 12
Secondary outcome [1] 0 0
Change From Baseline in Average Daily Normalized "On" Time Without Troublesome Dyskinesia at Week 12 - Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. "On" time without troublesome dyskinesia (involuntary muscle movement) is defined as "On" time without dyskinesia and "On" time with non-troublesome dyskinesia. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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. Positive change from Baseline for "on" time without troublesome dyskinesia indicates improvement.
Timepoint [1] 0 0
Baseline, Week 12
Secondary outcome [2] 0 0
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Summary Index at Week 12 - The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The PDQ-39 Summary Index is the sum of all answers divided by the highest score possible (i.e. number of answers multiplied by 4) which is multiplied by 100 to put the score on a 0-100 scale. Higher scores are associated with more severe symptoms.
Timepoint [2] 0 0
Baseline, Week 12
Secondary outcome [3] 0 0
Clinical Global Impression - Status (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Week 12 - The CGI-S is a global assessment by the Investigator of current symptomatology and impact of illness on functioning. The ratings of the CGI-S are as follows: 1 = normal, 2 = borderline ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = among the most extremely ill. The CGI-I is a global assessment by the Investigator of the change in clinical status since the start of treatment. The CGI-I ratings are as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse.
Timepoint [3] 0 0
Baseline, Week 12
Secondary outcome [4] 0 0
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score at Week 12 - The 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 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.
Timepoint [4] 0 0
Baseline, Week 12
Secondary outcome [5] 0 0
Change From Baseline in UPDRS Part III Score at Week 12 - The 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 provided to the 14 Part III questions, each of which are measured on a 5-point scale (0-4). The Part III score ranges from 0-108 and higher scores are associated with more disability.
Timepoint [5] 0 0
Baseline, Week 12
Secondary outcome [6] 0 0
Change From Baseline in EuroQual Quality of Life - 5 Dimensions (EQ-5D) Summary Index at Week 12 - The EQ-5D is a participant answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that essentially attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 to 1.00 with positive change indicating improvement.
Timepoint [6] 0 0
Baseline, Week 12
Secondary outcome [7] 0 0
Change From Baseline in Zarit Burden Interview (ZBI) Total Score at Week 12 - The ZBI is a 22-item questionnaire regarding the caregiver/subject relationship and evaluates the caregiver's health condition, psychological well-being, finances and social life. Each question is answered on a 5-point scale (0=Never, 1=Rarely, 2=Sometimes, 3=Quite frequently, and 4= Nearly always). The caregiver burden is evaluated by the total score (Range 0 to 88) obtained from the sum of the answers to the 22 questions. Higher scores are associated with a higher level of burden for the caregiver.
Timepoint [7] 0 0
Baseline, Week 12
Secondary outcome [8] 0 0
Change From Baseline in Average Daily Normalized "On" Time With Troublesome Dyskinesia at Week 12 - Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic 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.
Timepoint [8] 0 0
Baseline, Week 12
Secondary outcome [9] 0 0
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Mobility Domain Score at Week 12 - The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Mobility (e.g., fear of falling when walking) includes 10 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness.
Timepoint [9] 0 0
Baseline, Week 12
Secondary outcome [10] 0 0
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Activities of Daily Living Domain Score at Week 12 - The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Activities of Daily Living (e.g., difficulty cutting food) includes 6 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness.
Timepoint [10] 0 0
Baseline, Week 12
Secondary outcome [11] 0 0
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Emotional Well-Being Domain Score at Week 12 - The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Emotional Well-being (e.g., feelings of isolation) includes 6 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness.
Timepoint [11] 0 0
Baseline, Week 12
Secondary outcome [12] 0 0
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Stigma Domain Score at Week 12 - The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Stigma (e.g., social embarrassment) consists of 4 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness.
Timepoint [12] 0 0
Baseline, Week 12
Secondary outcome [13] 0 0
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Social Support Domain Score at Week 12 - The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Social Support includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness.
Timepoint [13] 0 0
Baseline, Week 12
Secondary outcome [14] 0 0
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Cognition Domain Score at Week 12 - The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Cognition includes 4 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness.
Timepoint [14] 0 0
Baseline, Week 12
Secondary outcome [15] 0 0
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Communication Domain Score at Week 12 - The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Communication includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness.
Timepoint [15] 0 0
Baseline, Week 12
Secondary outcome [16] 0 0
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Bodily Discomfort Domain Score at Week 12 - The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Bodily Discomfort includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness.
Timepoint [16] 0 0
Baseline, Week 12
Secondary outcome [17] 0 0
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at Week 12 - The UPDRS is an Investigator-used rating tool to follow the longitudinal 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 0-16 and higher scores are associated with more disability.
Timepoint [17] 0 0
Baseline, Week 12
Secondary outcome [18] 0 0
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score at Week 12 - The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part IV Score is the sum of the answers to the 11 questions that comprise Part IV, each of which are measured on a 5-point scale (0-4) or a 2-point scale (0 or 1). The Part IV score ranges from 0-23 and higher scores are associated with more disability.
Timepoint [18] 0 0
Baseline, Week 12
Secondary outcome [19] 0 0
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Questions 32, 33, and 34 at Week 12 - The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. Questions 32, 33, and 34 on UPDRS Part IV was totaled to evaluate dyskinesias. Each of these questions is measured on a 5-point scale (0-4). The Part IV dyskinesia score will range from 0-12 and higher scores are associated with more disability.
Timepoint [19] 0 0
Baseline, Week 12
Secondary outcome [20] 0 0
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at Week 12 - The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale. The total score will range from 0-176, with 176 representing the worst (total) disability, and 0 no disability.
Timepoint [20] 0 0
Baseline, Week 12
Secondary outcome [21] 0 0
Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Visual Analogue Scale (VAS) at Week 12 - The EQ VAS records the participant's self-rated health on a scale from 0-100 where 100 is the 'best imaginable health state' and 0 is the 'worst imaginable health state.'
Timepoint [21] 0 0
Baseline, Week 12
Secondary outcome [22] 0 0
Employment Impairment (EMP) I Status at Baseline - The EMP instruments are designed to collect information regarding employment and ability to run a household. EMP I questions include: Are you currently in paid employment? (If yes, at which percentage have you been working during the last 4 weeks?); Have you got someone to run your household for you? (If yes, how much time per week does he/she spend in your household?); Are you retired? (If yes, for which reason?).
Timepoint [22] 0 0
Baseline
Secondary outcome [23] 0 0
Employment Impairment (EMP) II Status at Week 12 - The EMP instruments are designed to collect information regarding employment and ability to run a household. EMP I questions include: Are you currently in paid employment? (If yes, at which percentage have you been working during the last 4 weeks?); Have you got someone to run your household for you? (If yes, how much time per week does he/she spend in your household?); Are you retired? (If yes, for which reason?) The retirement question (from EMP I) is excluded from the EMP II instrument.
Timepoint [23] 0 0
Week 12 (or early termination)

Eligibility
Key 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
Minimum age
30 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
New Zealand
State/province [10] 0 0
Auckland
Country [11] 0 0
New Zealand
State/province [11] 0 0
Christchurch
Country [12] 0 0
New Zealand
State/province [12] 0 0
Hamilton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie (prior sponsor, Abbott)
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Quintiles, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00660387
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janet Benesh
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Other publications