Open-Label, 12-Month Safety and Efficacy Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Parkinson's Disease Subjects
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 62
- Locations
- 22
- Primary Endpoint
- Number of Participants With Sleep Attacks at Baseline and Endpoint
Study Overview
Brief Summary
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
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 30 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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)
Arms & Interventions
Levodopa-Carbidopa Intestinal Gel (LCIG)
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.
Intervention: Levodopa-carbidopa intestinal gel (Drug)
Levodopa-Carbidopa Intestinal Gel (LCIG)
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.
Intervention: CADD-Legacy® 1400 ambulatory infusion pump (Device)
Levodopa-Carbidopa Intestinal Gel (LCIG)
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.
Intervention: PEG tube (Device)
Levodopa-Carbidopa Intestinal Gel (LCIG)
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.
Intervention: J-tube (Device)
Outcomes
Primary Outcomes
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.
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 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.
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.
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.
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 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 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 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 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.
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 Clinical Chemistry Parameters
Time Frame: 12 months
Terms abbreviated in the table include upper limit of normal (ULN), male (m), and female (f).
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.
Secondary Outcomes
- Change From Baseline in Average Daily "Off" Time at Endpoint(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(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(Baseline, Endpoint (Month 12 or last post-baseline visit))
- Change From Baseline in Average Daily "On" Time Without Troublesome Dyskinesia at Month 12(Baseline, Endpoint (Month 12 or last post-baseline visit))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Summary Index at Endpoint(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(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(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(Baseline, Endpoint (Month 12 or last post-baseline visit))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Stigma Domain Score at Endpoint(Baseline, Endpoint (Month 12 or last post-baseline visit))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Communication Domain Score at Endpoint(Baseline, Endpoint (Month 12 or last post-baseline visit))
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at Endpoint(Baseline, Endpoint (Month 12 or last post-baseline visit))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Mobility Domain Score at Endpoint(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(Baseline, Endpoint (Month 12 or last post-baseline visit))
- Change From Baseline in Average Daily Normalized "On" Time With Troublesome Dyskinesia at Endpoint(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(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(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(Baseline, Endpoint (Month 12 or last post-baseline visit))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Cognition Domain Score at Endpoint(Baseline, Endpoint (Month 12 or last post-baseline visit))
- Change From Baseline in Zarit Burden Interview (ZBI) Total Score at Endpoint(Baseline, Endpoint (Month 12 months or last post-baseline visit))
- Change From Baseline in Parkinson's Disease Questionnaire (PDQ-39) Bodily Discomfort Domain Score at Endpoint(Baseline, Endpoint (Month 12 or last post-baseline visit))
- Change From Baseline in EuroQol Quality of Life Scale (EQ-5D) Summary Index at Endpoint(Baseline, Endpoint (Month 12 or last post-baseline visit))