DyskinesiasPhase 3NCT00360568
Safety/Efficacy Study of Levodopa-Carbidopa Intestinal Gel in Parkinson's Subjects
A Phase 3 study testing Levodopa-carbidopa intestinal gel, CADD-Legacy® 1400 ambulatory infusion pump and PEG tube in people with Dyskinesias and Parkinson's Disease, run by AbbVie (prior sponsor, Abbott) at 22 sites in 3 countries.
Trial summary
Long term safety and efficacy (12 months) of levodopa-carbidopa intestinal gel. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Dyskinesias, Parkinson's Disease, Severe Motor Fluctuations
- What is being tested?
- Levodopa-carbidopa intestinal gel, CADD-Legacy® 1400 ambulatory infusion pump and PEG tube
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 22 sitesin 3 countries
- Study dates
- Jun 2009to Oct 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Idiopathic Parkinson's disease (PD) according to United Kingdon Parkinson's Disease Society (UKPDS) Brain Bank Criteria
- Levodopa-responsive with severe motor fluctuations
- Completion of protocol S187.3.001 (NCT00357994) or S187.3.002 (NCT00660387) and continue to meet the inclusion criteria for the preceding study
Who cannot join
- Patients with medically relevant abnormal findings (labs, electrocardiogram [ECG], physical examination, adverse events, psychiatric, neurological or behavioral disorders, etc.) at end of the double-blind phase (Week 12) of Study S187.3.001 (NCT00357994) or Study S187.3.002 (NCT00660387)
Trial locations and contacts
22 sites in 3 countries.
22 sites in 3 countries
United States16 sites
Site Reference ID/Investigator# 45862
Baltimore, Maryland, 21201
Site Reference ID/Investigator# 45869
Birmingham, Alabama, 35222
Site Reference ID/Investigator# 45857
Bradenton, Florida, 34205
Site Reference ID/Investigator# 45887
Burlington, Vermont, 05401
Site Reference ID/Investigator# 45874
Chicago, Illinois, 60611
Site Reference ID/Investigator# 45878
Cincinnati, Ohio, 45267
Site Reference ID/Investigator# 45850
Cleveland, Ohio, 44195-0001
Site Reference ID/Investigator# 45834
Fountain Valley, California, 92708
Site Reference ID/Investigator# 45863
Gainesville, Florida, 32610
Site Reference ID/Investigator# 45868
Lexington, Kentucky, 40536
Site Reference ID/Investigator# 45854
Los Angeles, California, 90033
Site Reference ID/Investigator# 45873
New York, New York, 10032
Site Reference ID/Investigator# 45856
Oceanside, California, 92056
Site Reference ID/Investigator# 45836
Port Charlotte, Florida, 33890
Site Reference ID/Investigator# 45861
St Louis, Missouri, 63110
Site Reference ID/Investigator# 45859
Washington D.C., District of Columbia, 20007
Germany4 sites
Site Reference ID/Investigator# 45828
Bochum, 44791
Site Reference ID/Investigator# 45829
Bremerhaven, 27574
Site Reference ID/Investigator# 45825
Hanover, 30625
Site Reference ID/Investigator# 54402
Tübingen, 72076
New Zealand2 sites
Site Reference ID/Investigator# 45884
Auckland, 1010
Site Reference ID/Investigator# 45885
Hamilton, 3204
About this study
Official title: Open-Label, 12-Month Safety and Efficacy Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Parkinson's Disease Subjects
Long term safety and efficacy (12 months) of levodopa-carbidopa intestinal gel.
Read the detailed description
Study S187.3.003 (NCT00360568) is a Phase 3, 12-month, open-label, multicenter continuation treatment study of the safety, tolerability, and efficacy of levodopa-carbidopa intestinal gel (LCIG) in the treatment of participants with levodopa-responsive Parkinson's disease (PD) with persistent motor fluctuations despite optimized treatment with available PD medications. All participants received LCIG.
Only participants who completed 12 weeks of double-blind, double-dummy treatment in Study S187.3.001 or S187.3.002 (NCT00357994/ NCT00660387) qualified for enrollment in this 12-month continuation treatment study.
- Conditions
- Dyskinesias, Parkinson's Disease, Severe Motor Fluctuations
- Being tested
- Levodopa-carbidopa intestinal gel, CADD-Legacy® 1400 ambulatory infusion pump, PEG tube, J-tube
- Keywords
- carbidopa, severe motor fluctuations, intestinal gel, levodopa, efficacy, levodopa carbidopa intestinal gel, dyskinesia, Parkinson's Disease, Duodopa, levodopa-carbidopa, DUOPA
- Medical subject headings
- Dyskinesias, Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Levodopa-carbidopa intestinal gelDrug
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).
CADD-Legacy® 1400 ambulatory infusion pumpDevice
PEG tubeDevice
percutaneous endoscopic gastrostomy tube
J-tubeDevice
jejunal tube
| Study group | Role | What they receive |
|---|---|---|
| Levodopa-Carbidopa Intestinal Gel (LCIG) | Experimental | All participants received LCIG, delivered through a percutaneous endoscopic gastrostomy with jejunal extension (PEG-J), administered for up to 12 months (52 weeks).
Starting dose of LCIG was based on the participant's optimized oral levodopa-carbidopa dose that the subject was receiving just prior to randomization in Study S187.3.001 (NCT00357994) or Study S187.3.002 (NCT00660387), administered in the morning of the first day following Study Day 86 of either of these 2 previous studies. The LCIG infusion was expected to infuse over approximately16 hours each day with a rate of infusion within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances. Receives: Drug: Levodopa-carbidopa intestinal gel; Device: CADD-Legacy® 1400 ambulatory infusion pump; Device: PEG tube; Device: J-tube |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs
AE=any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that: results in death; is life-threatening (an event in which the subject was at risk of death at the time of the event); requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical events. Treatment-emergent events (TEAE or TESAE)=those starting after the first dose of study drug. Severe=severity reported as 'severe' or missing. Possibly or Probably Treatment Related=drug-event relationship reported as 'possible', 'probable' or missing. Death=a fatal outcome of an SAE or AE.
Measured: From study enrollment to the end of study or early termination of treatment, including the removal of PEG-J, plus 30 days.
Number of Participants With Device Complications
Complications of the infusion device were collected. Pump, intestinal tube, PEG, stoma, and other complications included (but were not limited to) device breakage, device leakage, device malfunction, device misuse, device occlusion, intentional and unintentional device removal by participant, complication of device insertion, device dislocation, device breakage, device dislocation, and device site reaction.
Measured: 12 months
Number of Participants With Potentially Clinically Significant Values for Hematology Parameters
Terms abbreviated in the table include females (f) and males (m).
Measured: 12 months
Number of Participants With Potentially Clinically Significant Values for Clinical Chemistry Parameters
Terms abbreviated in the table include upper limit of normal (ULN), male (m), and female (f).
Measured: 12 months
Number of Participants With Potentially Clinically Significant Vital Sign Parameters
Terms abbreviated in the table include supine systolic blood pressure (SuSBP), standing systolic blood pressure (StSBP), orthostatic systolic blood pressure (OSBP), supine diastolic blood pressure (SuDBP), standing diastolic blood pressure (StDBP), orthostatic diastolic blood pressure (ODBP), supine pulse (SuP) in beats per minute (bpm), standing pulse (StP), and body temperature (Temp). Increase and decrease are signified by ↑ and ↓, respectively.
Measured: 12 months
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters
Terms abbreviated in the table include heart rate (HR) in beats per minute (bpm), PR interval (PRI), QT interval corrected for heart rate using Bazett's formula (QTcB), and QT interval corrected for heart rate using Fridericia's formula (QTcF). Increase and decrease are signified by ↑ and ↓, respectively.
Measured: 12 months
Number of Participants With Sleep Attacks at Baseline and Endpoint
To prospectively monitor for the possible development of sleep attacks, participants were asked if they had experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Summary of Minnesota Impulsive Disorder Interview (MIDI) Assessment of Intense Impulsive Behavior at Baseline (BL) and Post-baseline (PBL)
The MIDI is a validated assessment of impulsive behavior consisting of a semistructured clinical interview assessing pathological gambling, trichotillomania (compulsive hair-pulling), kleptomania (compulsive stealing), pyromania (compulsive fire-setting), intermittent explosive disorder, compulsive buying, and compulsive sexual behavior.
Measured: Baseline, Post-baseline (up to Month 12)
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Endpoint
The AIMS is an investigator-completed rating scale that has a total of 12 items rating involuntary movements of various areas of the participant's body. Items 1 through 10 are rated on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe), and items 11 and 12 are yes/no questions concerning problems with teeth or dentures. The total AIMS score was calculated by summing items 1-10, with a possible range of 0-40; a negative change indicates improvement. The AIMS was to be performed at consistent times, when the subject was experiencing his/her worst "On" time (dyskinesia [involuntary muscle movement]).
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Number of Participants With Confirmed Cases of Melanoma
A comprehensive assessment for the presence of melanoma was performed during the screening period and at early termination/end of study by a dermatologist experienced with the diagnosis of the condition. If a suspicious lesion was present, a biopsy was obtained for proper diagnosis.
Measured: up to Month 12
Number of Participants With Clinically Significant Neurological Examination Findings
The neurologic examination was to be done during "On" time. The neurological examination assessed: cranial nerves - assessment of cranial nerves II - XII, excluding fundoscopic examination; motor system - assessment of tone, strength, and abnormal movements; sensory system - including light touch, pinprick, joint position, and vibratory sense; reflexes - assessment of deep tendon reflexes and plantar responses (Babinski sign); coordination - assessment of upper and lower extremities; gait - assessment of base and tandem gait; station - assessment of posture and stability.
Measured: up to 12 months
Columbia-Suicide Severity Rating Scale (C-SSRS) Findings
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a systematically administered instrument developed to track suicidal adverse events across a treatment study. The instrument is designed to assess suicidal behavior and ideation, track and assess all suicidal events, as well as the lethality of attempts. Suicidal ideation categories include the following: wish to be dead; nonspecific active suicidal thoughts; active suicidal ideation without intent to act; active suicidal ideation with some intent to act but no plan; active suicidal ideation with plan and intent. Suicidal behavior categories include the following: actual attempt; interrupted attempt; aborted attempt; preparatory acts or behavior; suicidal behavior; completed suicide.
Measured: up to 12 months
Number of Participants Taking at Least 1 Concomitant Medication During the Study
Concomitant medications include medications started on or after the first open-label LCIG infusion as well as medications started prior to the first open-label infusion but continued during the study.
Measured: 12 months
Secondary outcomes (21)
Change From Baseline in Average Daily "Off" Time at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Average Daily Normalized "On" Time With Troublesome Dyskinesia at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Average Daily "On" Time Without Troublesome Dyskinesia at Month 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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Clinical Global Impression - Status (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at Endpoint
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 representing no disability.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Summary Index at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Mobility Domain Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Activities of Daily Living Domain Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Emotional Well-Being Domain Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Stigma Domain Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Social Support Domain Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Cognition Domain Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Communication Domain Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Bodily Discomfort Domain Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Summary Index at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Visual Analogue Scale (VAS) at Endpoint
The EQ-5D 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.'
Measured: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Zarit Burden Interview (ZBI) Total Score at Endpoint
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.
Measured: Baseline, Endpoint (Month 12 months or last post-baseline visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2006 (estimated)
- Study startJun 2009
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DyskinesiasStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie (prior sponsor, Abbott)
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Responsible party
- Sponsor
- Investigators
- Janet Benesh, Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00360568
- Sponsor's protocol ID
- S187.3.003
- Other IDs
- 2006-000578-53
- Status last verified
- Jan 2015
- First submitted
- 3 Aug 2006
- Last updated
- 16 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label, 12-Month Safety and Efficacy Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Parkinson's Disease Subjects
- ClinicalTrials.gov ID
- NCT00360568
- Acronym / sponsor ID
- S187.3.003
- Conditions
- Dyskinesias, Parkinson's Disease, Severe Motor Fluctuations
- Keywords
- carbidopa, severe motor fluctuations, intestinal gel, levodopa, efficacy, levodopa carbidopa intestinal gel, dyskinesia, Parkinson's Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- AbbVie (prior sponsor, Abbott)Industry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Study start
- Jun 2009
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 4 Aug 2006 (estimated)
- Results
- Posted 16 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Long term safety and efficacy (12 months) of levodopa-carbidopa intestinal gel.
Detailed description
Study S187.3.003 (NCT00360568) is a Phase 3, 12-month, open-label, multicenter continuation treatment study of the safety, tolerability, and efficacy of levodopa-carbidopa intestinal gel (LCIG) in the treatment of participants with levodopa-responsive Parkinson's disease (PD) with persistent motor fluctuations despite optimized treatment with available PD medications. All participants received LCIG.
Only participants who completed 12 weeks of double-blind, double-dummy treatment in Study S187.3.001 or S187.3.002 (NCT00357994/ NCT00660387) qualified for enrollment in this 12-month continuation treatment study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Levodopa-Carbidopa Intestinal Gel (LCIG) | Experimental | Drug: Levodopa-carbidopa intestinal gel, Device: CADD-Legacy® 1400 ambulatory infusion pump, Device: PEG tube, Device: J-tubeAll participants received LCIG, delivered through a percutaneous endoscopic gastrostomy with jejunal extension (PEG-J), administered for up to 12 months (52 weeks). Starting dose of LCIG was based on the participant's optimized oral levodopa-carbidopa dose that the subject was receiving just prior to randomization in Study S187.3.001 (NCT00357994) or Study S187.3.002 (NCT00660387), administered in the morning of the first day following Study Day 86 of either of these 2 previous studies. The LCIG infusion was expected to infuse over approximately16 hours each day with a rate of infusion within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Idiopathic Parkinson's disease (PD) according to United Kingdon Parkinson's Disease Society (UKPDS) Brain Bank Criteria
- Levodopa-responsive with severe motor fluctuations
- Completion of protocol S187.3.001 (NCT00357994) or S187.3.002 (NCT00660387) and continue to meet the inclusion criteria for the preceding study
Key exclusion criteria (1 listed)
- Patients with medically relevant abnormal findings (labs, electrocardiogram [ECG], physical examination, adverse events, psychiatric, neurological or behavioral disorders, etc.) at end of the double-blind phase (Week 12) of Study S187.3.001 (NCT00357994) or Study S187.3.002 (NCT00660387)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Levodopa-carbidopa intestinal gelInfusion 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 | Levodopa-Carbidopa Intestinal Gel (LCIG) |
| CADD-Legacy® 1400 ambulatory infusion pump | Device | Levodopa-Carbidopa Intestinal Gel (LCIG) |
| PEG tubepercutaneous endoscopic gastrostomy tube | Device | Levodopa-Carbidopa Intestinal Gel (LCIG) |
| J-tubejejunal tube | Device | Levodopa-Carbidopa Intestinal Gel (LCIG) |
Primary outcome
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs
Time frame: From study enrollment to the end of study or early termination of treatment, including the removal of PEG-J, plus 30 days.
AE=any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that: results in death; is life-threatening (an event in which the subject was at risk of death at the time of the event); requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical events. Treatment-emergent events (TEAE or TESAE)=those starting after the first dose of study drug. Severe=severity reported as 'severe' or missing. Possibly or Probably Treatment Related=drug-event relationship reported as 'possible', 'probable' or missing. Death=a fatal outcome of an SAE or AE.
Number of Participants With Device Complications
Time frame: 12 months
Complications of the infusion device were collected. Pump, intestinal tube, PEG, stoma, and other complications included (but were not limited to) device breakage, device leakage, device malfunction, device misuse, device occlusion, intentional and unintentional device removal by participant, complication of device insertion, device dislocation, device breakage, device dislocation, and device site reaction.
Number of Participants With Potentially Clinically Significant Values for Hematology Parameters
Time frame: 12 months
Terms abbreviated in the table include females (f) and males (m).
Number of Participants With Potentially Clinically Significant Values for Clinical Chemistry Parameters
Time frame: 12 months
Terms abbreviated in the table include upper limit of normal (ULN), male (m), and female (f).
Number of Participants With Potentially Clinically Significant Vital Sign Parameters
Time frame: 12 months
Terms abbreviated in the table include supine systolic blood pressure (SuSBP), standing systolic blood pressure (StSBP), orthostatic systolic blood pressure (OSBP), supine diastolic blood pressure (SuDBP), standing diastolic blood pressure (StDBP), orthostatic diastolic blood pressure (ODBP), supine pulse (SuP) in beats per minute (bpm), standing pulse (StP), and body temperature (Temp). Increase and decrease are signified by ↑ and ↓, respectively.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters
Time frame: 12 months
Terms abbreviated in the table include heart rate (HR) in beats per minute (bpm), PR interval (PRI), QT interval corrected for heart rate using Bazett's formula (QTcB), and QT interval corrected for heart rate using Fridericia's formula (QTcF). Increase and decrease are signified by ↑ and ↓, respectively.
Number of Participants With Sleep Attacks at Baseline and Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
To prospectively monitor for the possible development of sleep attacks, participants were asked if they had experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness.
Summary of Minnesota Impulsive Disorder Interview (MIDI) Assessment of Intense Impulsive Behavior at Baseline (BL) and Post-baseline (PBL)
Time frame: Baseline, Post-baseline (up to Month 12)
The MIDI is a validated assessment of impulsive behavior consisting of a semistructured clinical interview assessing pathological gambling, trichotillomania (compulsive hair-pulling), kleptomania (compulsive stealing), pyromania (compulsive fire-setting), intermittent explosive disorder, compulsive buying, and compulsive sexual behavior.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
The AIMS is an investigator-completed rating scale that has a total of 12 items rating involuntary movements of various areas of the participant's body. Items 1 through 10 are rated on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe), and items 11 and 12 are yes/no questions concerning problems with teeth or dentures. The total AIMS score was calculated by summing items 1-10, with a possible range of 0-40; a negative change indicates improvement. The AIMS was to be performed at consistent times, when the subject was experiencing his/her worst "On" time (dyskinesia [involuntary muscle movement]).
Number of Participants With Confirmed Cases of Melanoma
Time frame: up to Month 12
A comprehensive assessment for the presence of melanoma was performed during the screening period and at early termination/end of study by a dermatologist experienced with the diagnosis of the condition. If a suspicious lesion was present, a biopsy was obtained for proper diagnosis.
Number of Participants With Clinically Significant Neurological Examination Findings
Time frame: up to 12 months
The neurologic examination was to be done during "On" time. The neurological examination assessed: cranial nerves - assessment of cranial nerves II - XII, excluding fundoscopic examination; motor system - assessment of tone, strength, and abnormal movements; sensory system - including light touch, pinprick, joint position, and vibratory sense; reflexes - assessment of deep tendon reflexes and plantar responses (Babinski sign); coordination - assessment of upper and lower extremities; gait - assessment of base and tandem gait; station - assessment of posture and stability.
Columbia-Suicide Severity Rating Scale (C-SSRS) Findings
Time frame: up to 12 months
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a systematically administered instrument developed to track suicidal adverse events across a treatment study. The instrument is designed to assess suicidal behavior and ideation, track and assess all suicidal events, as well as the lethality of attempts. Suicidal ideation categories include the following: wish to be dead; nonspecific active suicidal thoughts; active suicidal ideation without intent to act; active suicidal ideation with some intent to act but no plan; active suicidal ideation with plan and intent. Suicidal behavior categories include the following: actual attempt; interrupted attempt; aborted attempt; preparatory acts or behavior; suicidal behavior; completed suicide.
Number of Participants Taking at Least 1 Concomitant Medication During the Study
Time frame: 12 months
Concomitant medications include medications started on or after the first open-label LCIG infusion as well as medications started prior to the first open-label infusion but continued during the study.
21 secondary outcomes
Change From Baseline in Average Daily "Off" Time at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Average Daily Normalized "On" Time With Troublesome Dyskinesia at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Average Daily "On" Time Without Troublesome Dyskinesia at Month 12
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Clinical Global Impression - Status (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Summary Index at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Mobility Domain Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Activities of Daily Living Domain Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Emotional Well-Being Domain Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Stigma Domain Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Social Support Domain Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Cognition Domain Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Communication Domain Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Bodily Discomfort Domain Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Summary Index at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Visual Analogue Scale (VAS) at Endpoint
Time frame: Baseline, Endpoint (Month 12 or last post-baseline visit)
Change From Baseline in Zarit Burden Interview (ZBI) Total Score at Endpoint
Time frame: Baseline, Endpoint (Month 12 months or last post-baseline visit)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janet Benesh study director
AbbVie
22 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Levodopa-carbidopa intestinal gel, CADD-Legacy® 1400 ambulatory infusion pump and PEG tube in people with Dyskinesias and Parkinson's Disease, run by AbbVie (prior sponsor, Abbott) at 22 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Germany, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs (time frame: From study enrollment to the end of study or early termination of treatment, including the removal of PEG-J, plus 30 days.). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2015.