Study of Efficacy, Safety and Tolerability of Levodopa-Carbidopa Intestinal Gel in Levodopa-Responsive Parkinson's Subjects

This study has been completed.
Sponsor:
Collaborator:
Quintiles
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT00660387
First received: April 15, 2008
Last updated: January 12, 2015
Last verified: January 2015
  Purpose

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.


Condition Intervention Phase
Advanced Parkinson's Disease
Drug: Levodopa carbidopa intestinal gel (LCIG)
Drug: Placebo Gel
Drug: Levodopa-carbidopa (LC) oral encapsulated immediate release (IR) tablets
Drug: Placebo (PBO) oral capsules
Device: CADD-Legacy® 1400 ambulatory infusion pump
Device: PEG tube
Device: J-tube
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Change From Baseline to Week 12 in Average Daily Normalized "Off" Time [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Average Daily Normalized "On" Time Without Troublesome Dyskinesia at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Summary Index at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Clinical Global Impression - Status (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in UPDRS Part III Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in EuroQual Quality of Life - 5 Dimensions (EQ-5D) Summary Index at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Zarit Burden Interview (ZBI) Total Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Average Daily Normalized "On" Time With Troublesome Dyskinesia at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Mobility Domain Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Activities of Daily Living Domain Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Emotional Well-Being Domain Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Stigma Domain Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Social Support Domain Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Cognition Domain Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Communication Domain Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Bodily Discomfort Domain Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Questions 32, 33, and 34 at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Visual Analogue Scale (VAS) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.'

  • Employment Impairment (EMP) I Status at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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?).

  • Employment Impairment (EMP) II Status at Week 12 [ Time Frame: Week 12 (or early termination) ] [ Designated as safety issue: No ]
    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.


Enrollment: 35
Study Start Date: December 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: 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)
Drug: Placebo (PBO) oral capsules Device: CADD-Legacy® 1400 ambulatory infusion pump Device: PEG tube
percutaneous endoscopic gastrostomy tube
Device: J-tube
jejunal tube
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.
Drug: Placebo Gel Drug: Levodopa-carbidopa (LC) oral encapsulated immediate release (IR) tablets Device: CADD-Legacy® 1400 ambulatory infusion pump Device: PEG tube
percutaneous endoscopic gastrostomy tube
Device: J-tube
jejunal tube

Detailed Description:

Study S187.3.001 (NCT00357994) and Study S187.3.002 (NCT00660387) were 2 identically designed, Phase 3, 12-week, randomized, double-blind, double-dummy, parallel-group, multicenter studies recruiting subjects from distinct sites. These studies evaluated the efficacy, safety, and tolerability of levodopa-carbidopa intestinal gel (LCIG) in the treatment of levodopa-responsive subjects with advanced PD who had persistent severe motor fluctuations, despite optimized treatment with oral levodopa-carbidopa, concomitant with other available antiparkinsonian medications. Participants were randomized to either LCIG active gel + placebo capsules or levodopa-carbidopa immediate release (IR) active capsules + placebo gel. Both treatment arms received the percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) procedure for gel administration, active LCIG or placebo gel. Data from these 2 studies were combined for analysis. The decision to combine the study data for analysis was made before enrollment was completed for both studies.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00660387

Locations
United States, Alabama
Site Reference ID/Investigator# 45931
Birmingham, Alabama, United States, 35222
United States, California
Site Reference ID/Investigator# 45910
Fountain Valley, California, United States, 92708
Site Reference ID/Investigator# 45925
Oceanside, California, United States, 92056
United States, Florida
Site Reference ID/Investigator# 45912
Port Charlotte, Florida, United States, 33890
United States, Illinois
Site Reference ID/Investigator# 45935
Chicago, Illinois, United States, 60611
United States, Kentucky
Site Reference ID/Investigator# 45930
Lexington, Kentucky, United States, 40536
United States, New York
Site Reference ID/Investigator# 45934
New York, New York, United States, 10032
United States, North Carolina
Site Reference ID/Investigator# 45929
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Site Reference ID/Investigator# 45908
Cincinnati, Ohio, United States, 45267
Site Reference ID/Investigator# 45922
Cleveland, Ohio, United States, 44195-0001
United States, Washington
Site Reference ID/Investigator# 45915
Kirkland, Washington, United States, 98034
New Zealand
Site Reference ID/Investigator# 45904
Auckland, New Zealand, 1010
Site Reference ID/Investigator# 45902
Christchurch, New Zealand, 8011
Site Reference ID/Investigator# 45905
Hamilton, New Zealand, 3204
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Quintiles
Investigators
Study Director: Janet Benesh AbbVie
  More Information

Additional Information:
No publications provided by AbbVie

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT00660387     History of Changes
Other Study ID Numbers: S187.3.002, 2007-003814-32
Study First Received: April 15, 2008
Results First Received: January 12, 2015
Last Updated: January 12, 2015
Health Authority: United States: Food and Drug Administration
New Zealand: Ministry of Health

Keywords provided by AbbVie:
levodopa-carbidopa
Carbidopa
levodopa
dyskinesia
Duodopa
levodopa-carbidopa intestinal gel
Severe Motor Fluctuations
levodopa/carbidopa suspension
DUOPA

Additional relevant MeSH terms:
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders
Carbidopa
Carbidopa, levodopa drug combination
Levodopa
Adjuvants, Immunologic
Anti-Dyskinesia Agents
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Dopamine Agonists
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 05, 2015