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A Study to Assess the Safety and Efficacy of Levodopa-carbidopa Intestinal Gel (LCIG) for the Treatment of Non-motor Symptoms in Patients With Advanced Parkinson's Disease

Primary Purpose

Advanced Parkinson's Disease

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Levodopa-Carbidopa Intestinal Gel

Percutaneous Endoscopic Gastrostomy with Jejunal Extension (PEG-J)

Levodopa-carbidopa Immediate Release (LC-IR) Tablets

About this trial

This is an interventional treatment trial for Advanced Parkinson's Disease focused on measuring Safety and efficacy, Advanced Parkinson's disease, levodopa-carbidopa intestinal gel,, carbidopa, levodopa, Non-Motor Symptom Scale

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subject must have a diagnosis of idiopathic Parkinson's disease (PD) according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria
Demonstrate persistent motor fluctuations in spite of individually optimized treatment
Subject must experience a minimum of 3 hours "Off" time

Exclusion Criteria:

Subject's PD diagnosis is unclear or there is a suspicion that the subject has a Parkinsonian syndrome such as secondary Parkinsonism (e.g., caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), Parkinson-plus syndrome (e.g., Multiple System Atrophy, Progressive Supranuclear Palsy, Diffuse Lewy Body Disease, Corticobasilar Degeneration), or other neurodegenerative disease that might mimic the symptoms of PD.
Subject has undergone neurosurgery for the treatment of Parkinson's disease
Subject for whom the placement of a PEG-J tube for LCIG treatment is contraindicated or is considered a high risk for the PEG-J procedure according to the gastroenterology evaluation (e.g., pathological changes of the gastric wall, inability to bring the gastric wall and abdominal wall together, blood coagulation disorders, peritonitis, acute pancreatitis, paralytic ileus).

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Levodopa-Carbidopa Intestinal Gel

Arm Description

Participants had the PEG-J tube placement procedure performed on Study Day 1 and, at the discretion of the investigator, began initiation and titration of LCIG infusion. Dosing was determined individually. The starting total daily dose of LCIG was based solely on the daily dose of the oral levodopa taken immediately prior to Study Day 1 and was adjusted to obtain the optimal clinical response for the individual participant. Participants received treatment for up to 60 weeks; participants who completed their Week 60 visit before LCIG was commercially available had the option to extend their LCIG therapy, if in the opinion of the investigator, the participant would benefit from continued LCIG treatment.

Outcomes

Primary Outcome Measures

Change From Baseline to Week 12 in the Non-Motor Symptom Scale (NMSS) Total Score

The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; the total score is obtained by summing the item scores. The NMSS total score ranges from 0 to 360 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Secondary Outcome Measures

Number of Participants Who Used Healthcare Resources During the First 4 Weeks

Use of healthcare resources was assessed by the investigator using the Health Resource Utilization Questionnaire (HRUQ), a questionnaire developed by the Sponsor regarding the use of healthcare resources due to the participant's Parkinson's disease. The Week 4 version of the questionnaire addressed the following questions during the first four weeks after the PEG-J procedure: Has the subject had a visit to an emergency room? Has the subject had a visit to an urgent care? Has the subject had an outpatient visit to a neurologist? Has the subject had an outpatient visit to a gastroenterologist, surgeon, or interventional radiologist? Has the subject had an outpatient visit to a primary care physician? Has the subject called the nursing support line? Has the subject called a physician?

Number of Participants With Adverse Events

Adverse events (AEs) related to treatment are those the investigator determined as having a reasonable possibility being related to study drug based on evidence to suggest a causal relationship between the study drug and the adverse event. A severe AE was defined as an adverse event that caused considerable interference with the participant's usual activities and might be incapacitating or life-threatening. Serious AEs were defined as those that were life-threatening or resulted in death, hospitalization or prolongation of hospitalization, a congenital anomaly, persistent or significant disability/incapacity, or important medical events requiring medical or surgical intervention to prevent a serious outcome.

Number of Participants Who Used Healthcare Resources Through Week 60

Use of healthcare resources was assessed by the investigator using the Health Resource Utilization Questionnaire (HRUQ), a questionnaire developed by the Sponsor regarding the use of healthcare resources due to the participant's Parkinson's disease. The standard version of the questionnaire addressed the following questions over the last 3 months: Has the subject had a visit to an emergency room? Has the subject had an outpatient visit to any of the following healthcare providers? Has the subject been visited in his or her place of residence by a health care professional? Has the subject received assistance from either of the following for their Parkinson's disease in their home? Has the subject needed to contact either of the following for immediate assistance related to their Parkinson's disease? Have family members or friends had to miss any paid work due to the subject's Parkinson's disease? Has the subject fallen during the past month?

Change From Baseline to Week 60 in the Non-Motor Symptom Scale (NMSS) Total Score

Change From Baseline in NMSS Cardiovascular Domain Score

The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS cardiovascular including falls domain score ranges from 0 to 24 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Change From Baseline in NMSS Sleep/Fatigue Domain Score

The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS sleep/fatigue domain score ranges from 0 to 48 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Change From Baseline in NMSS Mood/Cognition Domain Score

The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS mood/cognition domain score ranges from 0 to 72 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Change From Baseline in NMSS Perceptual Problems/Hallucinations Domain Score

The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS perceptual problems/hallucinations domain score ranges from 0 to 36 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Change From Baseline in NMSS Attention/Memory Domain Score

The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS attention/memory domain score ranges from 0 to 36 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Change From Baseline in NMSS Gastrointestinal Tract Domain Score

The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS gastrointestinal tract domain score ranges from 0 to 36 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Change From Baseline in NMSS Urinary Domain Score

The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS urinary domain score ranges from 0 to 36 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Change From Baseline in NMSS Sexual Function Domain Score

The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS sexual function domain score ranges from 0 to 24 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Change From Baseline in NMSS Miscellaneous Domain Score

The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS miscellaneous domain score ranges from 0 to 48 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Change From Baseline in Mean Daily Normalized "Off" Time Based on Parkinson's Disease Diary

The Parkinson's Disease Diary was completed by the participant for 3 consecutive days prior to each visit for the full 24 hours of each day. Participants recorded whether they had been "On," "Off," or "Asleep" and the severity of their dyskinesias (troublesome or not troublesome) for each 30-minute period during their normal waking time and upon awakening from time asleep. "Off" time was defined as time when medication has worn off and was no longer providing benefit with regard to mobility, slowness, and stiffness. Parkinson's Disease Diary times were normalized to a 16-hour waking time to account for variation in participants' sleep time. Normalized PD Diary times at a given visit were calculated as the average normalized time from the PD Diary for the 3 days prior to the visit.

Change From Baseline in Mean Daily Normalized "On" Time Without Troublesome Dyskinesia Based on PD Diary

The PD Diary was completed by the participant for 3 consecutive days prior to each visit. Participants recorded whether they had been "On," "Off," or "Asleep" and the severity of their dyskinesias (troublesome or not troublesome) for each 30-minute period during their normal waking time and upon awakening from sleep. "On" was defined as time when medication was providing benefit with regard to mobility, slowness, and stiffness. "On" time without troublesome dyskinesia is a composite of "On" time without dyskinesia (involuntary twisting, turning movements which are an effect of medication) plus "On" time with non-troublesome dyskinesia (dyskinesia that does not interfere with function or cause meaningful discomfort). PD Diary times were normalized to a 16-hour waking time to account for variation in participants' sleep time. Normalized PD Diary times at a given visit were calculated as the average normalized time from the PD Diary for the 3 days prior to the visit.

Change From Baseline for Unified Parkinson's Disease Rating Scale (UPDRS) Total Score

The Unified Parkinson's Disease Rating Scale (UPDRS) is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater. The UPDRS was made up of the following sections: Part I - Mentation, Behavior, and Mood Part II - Activities of Daily Living Part III - Motor Examination Part IV - Complications of Therapy (including dyskinesias) Part V - Modified Hoehn and Yahr Staging The Total UPDRS score includes 31 items contributing to three subscales: (I) Mentation, Behavior, and Mood; (II) Activities of Daily Living; and (III) Motor Examination. Each question is answered on a scale from 0 (None) to 4 (Severe); Some questions require multiple grades assigned to each extremity. The UPDRS Total score was computed as the sum of these 3 UPDRS subscales and ranged from 0 to 176, with 176 representing the worst (total) disability, and 0 no disability.

Change From Baseline in UPDRS Part I: Mentation, Behavior, and Mood Score

The Unified Parkinson's Disease Rating Scale (UPDRS) is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater. The UPDRS was made up of the following sections: Part I - Mentation, Behavior, and Mood Part II - Activities of Daily Living Part III - Motor Examination Part IV - Complications of Therapy (including dyskinesias) Part V - Modified Hoehn and Yahr Staging The mentation, behavior, and mood score includes 4 items addressing intellectual impairment, thought disorder, motivation/initiative, and depression. Each question is answered on a scale from 0 (None) to 4 (Severe). The UPDRS Part I: mentation, behavior, and mood score was computed as the sum of these items and ranged from 0 (not affected) to 16 (most severely affected).

Change From Baseline in UPDRS Part II: Activities of Daily Living (ADL) Score

The Unified Parkinson's Disease Rating Scale (UPDRS) is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater. The UPDRS was made up of the following sections: Part I - Mentation, Behavior, and Mood Part II - Activities of Daily Living Part III - Motor Examination Part IV - Complications of Therapy (including dyskinesias) Part V - Modified Hoehn and Yahr Staging The activities of daily living score includes 13 items addressing speech, salivation, swallowing, handwriting, cutting food, dressing, hygiene, turning in bed, falling, freezing, walking, tremor, and sensory complaints. Each question is answered on a scale from 0 (Normal) to 4 (Severe). The UPDRS Part II: activities of daily living score was computed as the sum of these items and ranged from 0 (not affected) to 52 (most severely affected).

Change From Baseline in UPDRS Part III: Motor Examination Score

The UPDRS is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater. The UPDRS was made up of the following sections: Part I - Mentation, Behavior, and Mood Part II - Activities of Daily Living Part III - Motor Examination Part IV - Complications of Therapy (including dyskinesias) Part V - Modified Hoehn and Yahr Staging The motor examination score includes 17 items addressing speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability, and body bradykinesia. Each question is answered on a scale from 0 (Normal) to 4 (Severe), some items include multiple grades for each extremity. The UPDRS Part III: motor examination score was computed as the sum of these items and ranged from 0 (not affected) to 108 (most severely affected).

Change From Baseline in UPDRS Part IV: Complications of Therapy Score

The UPDRS is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater. The UPDRS was made up of the following sections: Part I - Mentation, Behavior, and Mood Part II - Activities of Daily Living Part III - Motor Examination Part IV - Complications of Therapy (including dyskinesias) Part V - Modified Hoehn and Yahr Staging The complications of therapy section includes 11 items addressing dyskinesia duration, disability, and pain, early morning dystonia, "offs"-predictable, "offs"-unpredictable, "offs"-sudden, "offs"-duration, anorexia-nausea-vomiting, sleep disturbance, and symptomatic orthostasis. Four questions are answered on a scale from 0 (Normal) to 4 (Severe) and seven on a binary scale where 0=No and 1=Yes. The UPDRS Part IV: complications of therapy score was computed as the sum of these items and ranged from 0 (not affected) to 23 (most severely affected).

Change From Baseline in UPDRS Dyskinesia Items Score

The UPDRS is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater. The UPDRS was made up of the following sections: Part I - Mentation, Behavior, and Mood Part II - Activities of Daily Living Part III - Motor Examination Part IV - Complications of Therapy (including dyskinesias) Part V - Modified Hoehn and Yahr Staging The dyskinesia items score includes questions 32, 33 and 34 from the complications of therapy section of the UPDRS which address dyskinesia duration, disability, and pain. Each question was answered on a scale from 0 (Normal) to 4 (Severe); the UPDRS dyskinesia items score was computed as the sum of these items and ranged from 0 (not affected) to 12 (most severely affected).

Change From Baseline in UPDRS Part V: Modified Hoehn and Yahr Staging Score

The UPDRS is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater. The UPDRS was made up of the following sections: Part I - Mentation, Behavior, and Mood Part II - Activities of Daily Living Part III - Motor Examination Part IV - Complications of Therapy (including dyskinesias) Part V - Modified Hoehn and Yahr Staging The modified Hoehn and Yahr scale is as follows: Stage 0: No signs of disease Stage 1.0: Symptoms are very mild; unilateral involvement only Stage 1.5: Unilateral and axial involvement Stage 2: Bilateral involvement without impairment of balance Stage 2.5: Mild bilateral disease with recovery on pull test Stage 3: Mild to moderate bilateral disease; some postural instability; physically independent Stage 4: Severe disability; still able to walk or stand unassisted Stage 5: Wheelchair bound or bedridden unless aided

Change From Baseline in Parkinson's Disease Questionnaire-39 Item (PDQ-39) Summary Index

The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). The PDQ-39 Summary Index (PDQ-SI) 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 where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness.

Change From Baseline in PDQ-39 Mobility Domain Score

The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness.

Change From Baseline in PDQ-39 Activities of Daily Living Domain Score

The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness.

Change From Baseline in PDQ-39 Emotional Well-Being Domain Score

The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness.

Change From Baseline in PDQ-39 Stigma Domain Score

The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness.

Change From Baseline in PDQ-39 Social Support Domain Score

The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness.

Change From Baseline in PDQ-39 Cognition Domain Score

The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness.

Change From Baseline in PDQ-39 Communication Domain Score

The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness.

Change From Baseline in PDQ-39 Bodily Discomfort Domain Score

The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness.

Percentage of Participants With a Patient Global Impression of Change (PGIC) Response of Improved

The PGIC is a 7-point response scale. Participants were asked to rate their change in status using the following 7-point scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. The responses of "Very much improved," "Much improved" and "Minimally improved" on the PGIC were used to define responders.

Treatment Satisfaction Questionnaire Scores

The Treatment Satisfaction Questionnaire (TSQ) is a single item instrument developed by the Sponsor on which the participant indicated their level of satisfaction or dissatisfaction with their PD treatment. The responses are recorded on a Likert-type scale (Very Satisfied, Satisfied, Somewhat Satisfied, Somewhat Dissatisfied, Dissatisfied, Very Dissatisfied).

Change From Baseline in Health-related Productivity

The Health-Related Productivity Questionnaire (HRPQ) is a generic measure of the impact of disease on the ability of the participant to be productive at paid employment or at performance of household chores. Questions inquire about the amount of time they were scheduled/planned to work, the number of the scheduled/planned hours they were able to work and their ability to be productive for the hours of work they did perform. Absenteeism: Number of hours not worked due to PD or it's treatments; Presenteeism: Number of hours of lost productivity while at work due to PD or it's treatments; Total hours lost: Number of hours lost due to absenteeism and presenteeism

Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Working Memory Between Errors Score at Week 12

CANTAB is a computer-based test of the participant's ability to retain spatial information and to manipulate remembered items in working memory. The Spatial Working Memory module requires that subjects find a blue token in a series of displayed boxes and use these to fill up an empty column, while not returning to boxes where a blue token has been previously found. The between errors score is the number of times the participant revisited a box in which a token was previously found; errors are calculated for 4-, 6-, and 8-box trials. Higher numbers indicate poorer performance.

Change From Baseline in CANTAB Spatial Working Memory Strategy Score at Week 12

CANTAB is a computer-based test of the participant's ability to retain spatial information and to manipulate remembered items in working memory. The Spatial Working Memory module requires that subjects find a blue token in a series of displayed boxes and use these to fill up an empty column, while not returning to boxes where a blue token has been previously found. The Strategy score represents the number of times a participant begins a search with the same box for 6- and 8-box problems. Minimum score is 8 and maximum score is 56. Higher numbers indicate poorer performance.

Change From Baseline in Controlled Oral Word Association Test (COWAT) Verbal Fluency Scores at Week 60

Letter fluency was assessed using a paper and pen test, in which participants were asked to generate as many words as possible in 60 seconds, starting with the letters F, A, or S. The COWAT All Letters score is the number of words recalled in all post-baseline assessments, regardless of letter used. The COWAT Baseline Letter score is the number of words recalled in post-baseline assessments that used the same letter as at Baseline.

Full Information

NCT ID

NCT01736176

First Posted

November 27, 2012

Last Updated

July 14, 2021

Sponsor

AbbVie (prior sponsor, Abbott)

1. Study Identification

Unique Protocol Identification Number

NCT01736176

Brief Title

A Study to Assess the Safety and Efficacy of Levodopa-carbidopa Intestinal Gel (LCIG) for the Treatment of Non-motor Symptoms in Patients With Advanced Parkinson's Disease

Official Title

An Open-Label, Two Part, Multicenter Study to Assess the Safety and Efficacy of Levodopa-Carbidopa Intestinal Gel (LCIG) for the Treatment of Non-Motor Symptoms in Subjects With Advanced Parkinson's Disease

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

March 2013 (undefined)

Primary Completion Date

March 2015 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AbbVie (prior sponsor, Abbott)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The primary objective of this study is to evaluate change in non-motor symptoms from baseline to Week 12 as measured by the Non-Motor Symptom Scale total score.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Parkinson's Disease

Keywords

Safety and efficacy, Advanced Parkinson's disease, levodopa-carbidopa intestinal gel,, carbidopa, levodopa, Non-Motor Symptom Scale

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Levodopa-Carbidopa Intestinal Gel

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Levodopa-Carbidopa Intestinal Gel

Other Intervention Name(s)

Duopa, Carbidopa-levodopa enteral suspension (CLES)

Intervention Description

Levodopa-carbidopa intestinal gel (LCIG) for upper-intestinal infusion is a suspension of levodopa (20 mg/mL) and carbidopa monohydrate (5 mg/mL) in an aqueous gel, administered continuously by a portable pump via a percutaneous endoscopic gastrojejunostomy (PEG-J) tube. The rate of LCIG infusion was expected to be within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances over a period of 16 consecutive hours.

Intervention Type

Procedure

Intervention Name(s)

Percutaneous Endoscopic Gastrostomy with Jejunal Extension (PEG-J)

Intervention Type

Drug

Intervention Name(s)

Levodopa-carbidopa Immediate Release (LC-IR) Tablets

Intervention Description

After LCIG initiation, participants could take prescribed oral levodopa-carbidopa immediate or continuous release (i.e., oral LC prescribed by the investigator) for nighttime use.

Primary Outcome Measure Information:

Title

Change From Baseline to Week 12 in the Non-Motor Symptom Scale (NMSS) Total Score

Description

Time Frame

Baseline and Week 12

Secondary Outcome Measure Information:

Title

Number of Participants Who Used Healthcare Resources During the First 4 Weeks

Description

Time Frame

Weeks 1-4

Title

Number of Participants With Adverse Events

Description

Time Frame

Weeks 1-4 and Overall (from Week 1 through 30 days after the end of the LCIG Treatment Period; median duration of LCIG device exposure was 428 days)

Title

Number of Participants Who Used Healthcare Resources Through Week 60

Description

Use of healthcare resources was assessed by the investigator using the Health Resource Utilization Questionnaire (HRUQ), a questionnaire developed by the Sponsor regarding the use of healthcare resources due to the participant's Parkinson's disease. The standard version of the questionnaire addressed the following questions over the last 3 months: Has the subject had a visit to an emergency room? Has the subject had an outpatient visit to any of the following healthcare providers? Has the subject been visited in his or her place of residence by a health care professional? Has the subject received assistance from either of the following for their Parkinson's disease in their home? Has the subject needed to contact either of the following for immediate assistance related to their Parkinson's disease? Have family members or friends had to miss any paid work due to the subject's Parkinson's disease? Has the subject fallen during the past month?

Time Frame

Week 60

Title

Change From Baseline to Week 60 in the Non-Motor Symptom Scale (NMSS) Total Score

Description

Time Frame

Baseline and Week 60

Title

Change From Baseline in NMSS Cardiovascular Domain Score

Description

The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS cardiovascular including falls domain score ranges from 0 to 24 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

Time Frame