Levodopa-Carbidopa Intestinal Gel Open-Label Study in Advanced Parkinson's Disease

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 regarding issues 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 \[involuntary muscle movement\]).

Time frame: Baseline, Endpoint (last Post-PEG Long-Term Period visit up to Day 378)

Population: Post-PEG Safety Data Set: participants who continued to the PEG-J surgery, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded); n=number of participants with assessment at timepoint.

Concomitant medications include those 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.

Time frame: Screening up to Day 378

Population: Safety Data Set: participants who were allocated to treatment, had started placement of NJ tube, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded).

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.

Time frame: Screening through Day 378 + 30 days

Population: Safety Data Set: participants who were allocated to treatment, had started placement of NJ tube, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded).

A comprehensive assessment for the presence of melanoma was performed during the screening period and at early termination or 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.

Time frame: Screening up to Day 378

Population: Safety Data Set: participants who were allocated to treatment, had started placement of NJ tube, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded).

Complications of the infusion device were collected during the NJ Test period. Pump, intestinal tube, NJ tube, 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 post-procedural hemorrhage.

Time frame: NJ Test Period (from 2 to 14 days)

Population: Safety Data Set: participants who were allocated to treatment, had started placement of NJ tube, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded).

Complications of the infusion device were collected during the PEG-J Surgery and Post-PEG Long-Term Treatment periods. Pump, PEG-J, 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 post-procedural hemorrhage.

Time frame: PEG-J Surgery Period (from 2 to 14 days) through the Long Term Treatment Period (Day 28 to Day 378)

Population: Post-PEG Safety Data Set: participants who continued to the PEG-J surgery, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded).

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.

Time frame: Screening through Day 378

Population: Post-PEG Safety Data Set: participants who continued to the PEG-J surgery, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded); n=number of participants with given assessment.

Terms abbreviated in the table include aspartate aminotransferase (AST), upper limit of normal (ULN), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), female (f), and male (m).

Time frame: Screening through Day 378

Population: Post-PEG Safety Data Set: participants who continued to the PEG-J surgery, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded); n=number of participants with assessment.

Potentially clinically significant values for red blood cells (RBCs), hemoglobin, and hematocrit are specified for females (f) and males (m) separately in the category rows.

Time frame: Screening through Day 378

Population: Post-PEG Safety Data Set: participants who continued to the PEG-J surgery, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded); n=number of participants with assessment.

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.

Time frame: up to 56 weeks

Population: Post-PEG Safety Data Set: participants who continued to the PEG-J surgery, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded); n=number of participants with assessment.

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. Those participants who reported 1 or more sleep attacks were asked to report the number of sleep attacks they experienced, whether they experienced sleepiness or drowsiness prior to the sleep attack, whether they experienced a 'bad' outcome or problem due to a sleep attack, and if so, how many 'bad' outcomes or problems they experienced.

Time frame: Baseline

Population: Post-PEG Safety Data Set: participants who continued to the PEG-J surgery, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded).

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. Those participants who reported 1 or more sleep attacks were asked to report the number of sleep attacks they experienced, whether they experienced sleepiness or drowsiness prior to the sleep attack, whether they experienced a 'bad' outcome or problem due to a sleep attack, and if so, how many 'bad' outcomes or problems they experienced.

Time frame: During the Post-PEG Long-Term Treatment Period (Day 28 through Day 378)

Population: Post-PEG Safety Data Set: participants who continued to the PEG-J surgery, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded) who had an assessment.

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.

Time frame: Baseline, during the Post-PEG Long-term Treatment Period (Day 28 through Day 378)

Population: Post-PEG Safety Data Set: participants who continued to the PEG-J surgery, and had at least 1 post-baseline safety evaluation (only participants lost to follow-up with no post-baseline information were excluded); n=number of participants with an assessment at timepoint.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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'.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.

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.

Time frame: Baseline, Endpoint (last post-baseline visit up to Day 378)

Population: Full Analysis Data Set: participants who had at least 1 post-baseline safety evaluation, a baseline efficacy evaluation, and had data for at least 1 post-baseline assessment of this efficacy measurement during the Post-PEG Long-Term Treatment Period.