Clinical Trial Results:
Open-Label Continuation Treatment Study with Levodopa-Carbidopa Intestinal Gel in Subjects with Advanced Parkinson's Disease and Severe Motor-Fluctuations Who Have Exhibited a Persistent and Positive Effect to Treatment in Previous Studies
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Summary
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EudraCT number |
2008-001329-33 |
Trial protocol |
PT CZ GB |
Global end of trial date |
30 Nov 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Nov 2022
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First version publication date |
05 Nov 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
S187.3.005
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00660673 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Abbvie Deutschland GmbH & Co.KG
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Sponsor organisation address |
AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
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Public contact |
Global Medical Services, AbbVie, 001 800-633-9110, abbvieclinicaltrials@abbvie.com
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Scientific contact |
Global Medical Services, AbbVie, 001 800-633-9110, abbvieclinicaltrials@abbvie.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Nov 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Nov 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to provide, under well-controlled conditions, continued access to LCIG treatment to subjects who had already participated in an open-label efficacy and safety study with the same treatment (Study S187-3-003 [2006-000578-53], Study S187-3-004 [2006-005186-18]), and in whom the need for such continuation is indicated, as confirmed by periodic evaluation, until the product becomes commercially available.
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Protection of trial subjects |
Subject read and understood the information provided about the study and gave written permission.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Nov 2009
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 12
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Country: Number of subjects enrolled |
Canada: 11
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Country: Number of subjects enrolled |
Czechia: 22
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Country: Number of subjects enrolled |
Israel: 9
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Country: Number of subjects enrolled |
New Zealand: 10
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Country: Number of subjects enrolled |
Poland: 4
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Country: Number of subjects enrolled |
Portugal: 14
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Country: Number of subjects enrolled |
Russian Federation: 43
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Country: Number of subjects enrolled |
Thailand: 13
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Country: Number of subjects enrolled |
United Kingdom: 11
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Country: Number of subjects enrolled |
United States: 113
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Worldwide total number of subjects |
262
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EEA total number of subjects |
40
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
133
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From 65 to 84 years |
129
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85 years and over |
0
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Recruitment
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Recruitment details |
Enrollment began in November 2009 and was completed in October 2012. Participants were enrolled at 61 sites in 11 countries: Australia, Canada, Czech Republic, Israel, New Zealand, Poland, Portugal, the Russian Federation, Thailand, the United Kingdom, and the United States. | ||||||||||||||||||
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Pre-assignment
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Screening details |
This study was an open-label extension study for participants with Parkinson's disease (PD) who had completed prior study S187.3.003 or S187.3.004. Participants were to receive continued access to levodopa-carbidopa intestinal gel (LCIG) in the extension study until treatment became commercially available in their home country. | ||||||||||||||||||
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Period 1
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Period 1 title |
LCIG Extension Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Levodopa-Carbidopa Intestinal Gel | ||||||||||||||||||
Arm description |
Participants received levodopa-carbidopa intestinal gel (LCIG), continuously administered through a percutaneous endoscopic gastrostomy with jejunal extension tube (PEG-J) directly into the jejunum via a portable pump during 16 hours of wakefulness. Initial dosing was based on the dosing regimen that the participant received during the previous LCIG study. Dosing was individually optimized and adjusted as clinically indicated. In addition to a morning dose (to prime the intestinal tube and rapidly achieve the therapeutic dose level) of 5 to 10 mL (100 to 200 mg levodopa), and the continuous infusion usually 2 to 6 mL/hour (40 to 120 mg levodopa/hour), participants were allowed to self-administer additional doses of LCIG to address immediate subjective needs (eg, deterioration of motor function). Participants received LCIG until it became commercially available. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Levodopa-Carbidopa Intestinal Gel
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Investigational medicinal product code |
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Other name |
Duodopa®, Duopa®, Carbidopa/levodopa enteral suspension (CLES)
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Pharmaceutical forms |
Intestinal gel
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Routes of administration |
Gastroenteral use
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Dosage and administration details |
LCIG is administered over approximately 16 waking hours.
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Baseline characteristics reporting groups
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Reporting group title |
LCIG Extension Study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Levodopa-Carbidopa Intestinal Gel
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Reporting group description |
Participants received levodopa-carbidopa intestinal gel (LCIG), continuously administered through a percutaneous endoscopic gastrostomy with jejunal extension tube (PEG-J) directly into the jejunum via a portable pump during 16 hours of wakefulness. Initial dosing was based on the dosing regimen that the participant received during the previous LCIG study. Dosing was individually optimized and adjusted as clinically indicated. In addition to a morning dose (to prime the intestinal tube and rapidly achieve the therapeutic dose level) of 5 to 10 mL (100 to 200 mg levodopa), and the continuous infusion usually 2 to 6 mL/hour (40 to 120 mg levodopa/hour), participants were allowed to self-administer additional doses of LCIG to address immediate subjective needs (eg, deterioration of motor function). Participants received LCIG until it became commercially available. | ||
Subject analysis set title |
Year 1
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received LCIG during Year 1 of the extension study.
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Subject analysis set title |
Year 2
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received LCIG during Year 2 of the extension study.
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Subject analysis set title |
Year 3
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received LCIG during Year 3 of the extension study.
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Subject analysis set title |
Year 4
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received LCIG during Year 4 of the extension study.
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Subject analysis set title |
Year 5
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received LCIG during Year 5 of the extension study.
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Subject analysis set title |
Year 6
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received LCIG during Year 6 of the extension study.
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Subject analysis set title |
Year 7
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received LCIG during Year 7 of the extension study.
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Subject analysis set title |
Year 8
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received LCIG during Year 8 of the extension study.
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Subject analysis set title |
Year 9
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received LCIG during Year 9 of the extension study.
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Subject analysis set title |
Year 10
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received LCIG during Year 10 of the extension study.
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Subject analysis set title |
> Year 10
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received LCIG after Year 10 of the extension study.
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End point title |
Number of Participants With Treatment-emergent Adverse Events [1] | ||||||||||||||||||
End point description |
Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) which started on or after the date of the first LCIG Infusion in this study and within 30 days of the date of the last PEG-J exposure.
At least possibly drug-related is defined as TEAEs assessed as having a "Possible," "Probable" or missing relationship to study drug.
Serious AEs included any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.
The severity of all AEs was characterized as mild, moderate or severe according to the following definitions:
Mild: usually transient and do not interfere with daily activities.
Moderate: low level of inconvenience or concern to the subject, may interfere with daily activities.
Severe: events interrupt the subject's usual daily activity.
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End point type |
Primary
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End point timeframe |
From first dose of LCIG in this study up to 30 days after the date of last PEG-J exposure; median duration of treatment was 1178 days, with a maximum of 4217 days (11.5 years).
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses were not conducted. |
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| Notes [2] - All participants who received LCIG in this extension study |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Participants With Device Complications | ||||||||||||||
End point description |
Device complications include complications with the pump, intestinal tube, PEG-J or stoma.
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End point type |
Secondary
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End point timeframe |
From first dose of LCIG in this study up to 30 days after the date of last PEG-J exposure; median duration of treatment was 1178 days.
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of Participants With Sleep Attacks | ||||||||||||||
End point description |
Participants were asked whether they 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. If yes, participants were asked if they suffered any "bad" outcome or problem from the falling asleep event.
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End point type |
Secondary
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End point timeframe |
Baseline (final assessment period of the previous open-label LCIG study) and every 6 months until final visit; median duration of treatment was 1178 days.
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| Notes [3] - 255 participants had post-baseline sleep attack data |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of Participants With Intense Impulsive Behavior | ||||||||||||||||||||||||||||||||||
End point description |
To monitor for the development of intense impulsive behavior the Minnesota Impulsive Disorder Interview (MIDI) was administered. The MIDI is a semi-structured clinical interview assessing pathological gambling, trichotillomania, kleptomania, pyromania, intermittent explosive disorder, compulsive buying, and compulsive sexual behavior.
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End point type |
Secondary
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End point timeframe |
Baseline (final assessment of the previous open-label LCIG study) and every 6 months until final visit; median duration of treatment was 1178 days.
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| Notes [4] - 256 participants had post-baseline MIDI data |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants Who Developed Melanoma | ||||||
End point description |
A comprehensive assessment for the presence of melanoma was performed at least once a year by a dermatologist.
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End point type |
Secondary
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End point timeframe |
Once per year during the study; median duration of treatment was 1178 days.
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants With Treatment-emergent Adverse Events of Special Interest (TE AESI) | ||||||||||||||||
End point description |
Adverse events of special interest (AESIs) were identified using standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (SMQ) or company MedDRA queries (CMQs). The AESI in the following categories were identified on the basis of review of the clinical program and postmarketing observations where the treatment system is commercially available.
- Procedure and device associated events;
- Polyneuropathy, included preferred terms in either the peripheral neuropathy or GuillainBarre syndrome standardized MedDRA query (narrow search), such as polyneuropathy, decreased vibratory sense, peripheral neuropathy, peripheral sensory neuropathy, neuralgia, demyelinating polyneuropathy, and sensory disturbance;
- Weight loss;
- Cardiovascular fatalities;
- Respiratory tract aspiration including aspiration pneumonia/pneumonitis.
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End point type |
Secondary
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End point timeframe |
From first dose of LCIG in this study up to 30 days after the date of last PEG-J exposure; median duration of treatment was 1178 days, with a maximum of 4217 days (11.5 years).
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Number of Participants With Any Suicidal Ideation or Behavior | ||||||||||||||
End point description |
The Columbia-Suicide Severity Rating Scale (C-SSRS) was implemented with Protocol Amendment 3 (20 March 2012) in order to assess suicidal behavior and ideation.
Suicidal ideation includes the wish to be dead, nonspecific active suicidal thoughts, active ideation without intent to act, active ideation with some intent to act, and active ideation with specific plan or intent. Suicidal behavior includes actual attempts, interrupted attempts, aborted attempts, completed suicide, and preparatory acts or behaviors.
The number of participants with affirmative responses on the C-SSRS at any time during the treatment period is reported.
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End point type |
Secondary
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End point timeframe |
Every 6 months (beginning with implementation of Protocol Amendment 3) until final visit; median duration of treatment was 1178 days.
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| Notes [5] - All participants who received LCIG in this extension study with available C-SSRS data |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of Participants With Potentially Clinically Significant Vital Sign Values | ||||||||||||||||||||||||||||||||||||||||
End point description |
A vital sign value was considered potentially clinically significant if it satisfied the pre-specified criteria presented in the table and was also more extreme than the participant's corresponding Baseline (BL) value.
Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), orthostatic change in blood pressure (supine to standing) pulse rate, temperature, and weight.
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End point type |
Secondary
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End point timeframe |
Baseline and every 6 months until final visit; median duration of treatment was 1178 days.
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| Notes [6] - 254 subjects had standing BP and pulse, temp and weight data; 253 had orthostatic change in BP data. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants With Potentially Clinically Significant Hematology Laboratory Values | ||||||||||||||||||||||||||||||||||
End point description |
A laboratory value was considered potentially clinically significant if it satisfied the pre-specified criteria presented in the table and was also more extreme than the participant's corresponding baseline value.
Hematoloty included red blood cell (RBC) count, white blood cell (WBC) count, haemoglobin, haematocrit, absolute neutrophil count (ANC), lymphocytes, eosinophils, platelets, monocytes, and mean corpuscular volume (MCV).
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End point type |
Secondary
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End point timeframe |
Baseline and every 6 months until final visit; median duration of treatment was 1178 days.
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| Notes [7] - 195 subjects had haematocrit, MCV and WBC differential post-baseline data; 194 had platelet data. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants With Potentially Clinically Significant Chemistry Laboratory Values | ||||||||||||||||||||||||||||||||||||
End point description |
A laboratory value was considered potentially clinically significant if it satisfied the pre-specified criteria presented in the table and was also more extreme than the participant's corresponding baseline value.
ULN = upper limit of normal
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End point type |
Secondary
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End point timeframe |
Baseline and every 6 months until final visit; median duration of treatment was 1178 days.
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| Notes [8] - 197 subjects had LDH post-baseline data; 95 subjects had BUN post-baseline data. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants With Vitamin Levels Outside of the Normal Range | ||||||||||||||||||||||
End point description |
Special tests for vitamin deficiencies (folic acid, vitamin B6, vitamin B12, methylmalonic acid [MMA], and homocysteine) were implemented with Protocol Amendment 2 (27 July 2011). The number of participants with vitamin levels outside of the normal range at any time post-baseline is reported for each vitamin tested.
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End point type |
Secondary
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End point timeframe |
Every 6 months (beginning with implementation of Protocol Amendment 2) until final visit; median duration of treatment was 1178 days.
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| Notes [9] - 212 subjects had vitamin B12 postbaseline data; 211 subjects had vitamin B6; and 213 had folate data |
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Number of Participants Receiving Concomitant Anti-Parkinson’s Disease Medications by Treatment Year | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Participants could use oral levodopa-carbidopa for scheduled or supplemental bedtime/overnight doses after the pump was disconnected for the night, or as rescue medication in case of acute deterioration caused by failure of the LCIG system such as tubes and/or the pump or the onset of an acute illness.
The initiation of additional concomitant PD medication was allowed at the discretion of the Investigator if medically indicated.
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End point type |
Secondary
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End point timeframe |
Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9, Year 10, > Year 10 (maximum time on treatment was approximately 11.5 years).
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change in Average Daily "Off" Time Based on the Parkinson’s Disease Symptom Diary at End of Treatment | ||||||||||||
End point description |
The PD symptom diary asks participants (or their caregivers) to indicate their status upon waking and every 30 minutes during their normal waking time according to the following categories: asleep, "off", "on" without dyskinesia, "on" with non-troublesome dyskinesia, or "on" with troublesome dyskinesia.
"Off" time was defined as time when medication had worn off and was no longer providing benefit with regard to mobility, slowness, and stiffness.
PD diary times were normalized to a 16-hour waking day and averaged for the 3 days prior to each study visit.
A negative change for "off" time indicates improvement. The PD diary assessment was implemented with Protocol amendment 4 (December 2013) for participants at United States (US) sites only.
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End point type |
Secondary
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End point timeframe |
Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
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| Notes [10] - Participants who were enrolled in the US and had at least 1 efficacy assessment in the curent study. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Average Daily "On" Time Without Troublesome Dyskinesia Based on the Parkinson’s Disease Symptom Diary at End of Treatment | ||||||||||||
End point description |
The PD diary asks participants (or their caregivers) to indicate their status upon waking and every 30 minutes during their normal waking time according to the following categories: asleep, "off", "on" without dyskinesia, "on" with non-troublesome dyskinesia, or "on" with troublesome dyskinesia.
"On" time is when medication is providing benefit with regard to mobility, slowness and stiffness. Dyskinesia is involuntary twisting, turning movements which are an effect of medication and occur during "on" time. Non-troublesome dyskinesia does not interfere with function or cause meaningful discomfort.
"On" time without troublesome dyskinesia is the sum of "on" time without dyskinesia and "on" time with non-troublesome dyskinesia. PD diary times were normalized to a 16-hour waking day and averaged for the 3 days prior to each study visit. A positive change indicates improvement.
The PD diary was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
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End point type |
Secondary
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End point timeframe |
Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
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| Notes [11] - Participants who were enrolled in the US and had at least 1 efficacy assessment in the current study |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Average Daily "On" Time With Troublesome Dyskinesia Based on the Parkinson’s Disease Symptom Diary at End of Treatment | ||||||||||||
End point description |
The PD diary asks participants (or their caregivers) to indicate their status upon waking and every 30 minutes during their normal waking time according to the following categories: asleep, "off", "on" without dyskinesia, "on" with non-troublesome dyskinesia, or "on" with troublesome dyskinesia.
"On" time is when medication is providing benefit with regard to mobility, slowness and stiffness. Dyskinesia is involuntary twisting, turning movements which are an effect of medication and occur during "on" time. Troublesome dyskinesia interferes with function or causes meaningful discomfort.
PD diary times were normalized to a 16-hour waking day and averaged for the 3 days prior to each study visit. A positive change indicates improvement.
The PD diary was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
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End point type |
Secondary
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End point timeframe |
Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
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| Notes [12] - Participants who were enrolled in the US and had at least 1 efficacy assessment in the current study |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at End of Treatment | ||||||||||||
End point description |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:
I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including dyskinesias).
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. A negative change from Baseline indicates improvement.
The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
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End point type |
Secondary
|
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End point timeframe |
Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
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| Notes [13] - 79 subjects had available data for change from initial LCIG infusion. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score at End of Treatment | ||||||||||||
End point description |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:
I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including dyskinesias).
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. A negative change from Baseline indicates improvement.
The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
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End point type |
Secondary
|
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End point timeframe |
Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
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| Notes [14] - 79 subjects had change from initial LCIG infusion data. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at End of Treatment | ||||||||||||
End point description |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:
I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including dyskinesias).
UPDRS Part III consists of 14 questions. Questions 20 - 26 are multi-part questions in that they are evaluated separately for multiple body parts. Counting each of these assessments leads to a total of 27 answers for Part III. The UPDRS 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. A negative change from Baseline indicates improvement.
The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
|
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End point type |
Secondary
|
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End point timeframe |
Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
|
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| Notes [15] - 79 subjects had change from initial LCIG infusion data. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at End of Treatment | ||||||||||||
End point description |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:
I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including dyskinesias).
The UPDRS 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 ranges from 0 - 176 with 176 representing the worst (total) disability, and 0 no disability. A negative change from Baseline indicates improvement.
The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
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End point type |
Secondary
|
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End point timeframe |
Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
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| Notes [16] - 79 subjects had change from initial LCIG infusion data. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score at End of Treatment | ||||||||||||
End point description |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:
I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including dyskinesias).
The UPDRS Part IV Score is the sum of all answers to the 11 questions that comprise Part IV, 4 of which are measured on a 5-point scale (0 – 4) and 7 which are measured on a 2-point scale (0 – 1). The Part IV score ranges from 0 – 23 and higher scores are associated with more disability. A negative change from Baseline indicates improvement.
The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
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End point type |
Secondary
|
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End point timeframe |
Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
|
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| Notes [17] - 79 subjects had change from initial LCIG infusion data. |
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| No statistical analyses for this end point | |||||||||||||
|
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End point title |
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Dyskinesia Score at End of Treatment | ||||||||||||
End point description |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:
I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including dyskinesias); and
The UPDRS Part IV Dyskinesia Score is the sum of Questions 32 (What proportion of the waking day are dyskinesias present?), 33 (How disabling are the dyskinesias?), and 34 (How painful are the dyskinesias?) on UPDRS Part IV, each of which are measured on a 5-point scale (0-4). The Part IV dyskinesia score ranges from 0 - 12 and higher scores are associated with more disability. A negative change from Baseline indicates improvement.
The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
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End point type |
Secondary
|
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End point timeframe |
Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
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|
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| Notes [18] - 79 subjects had change from initial LCIG infusion data. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in Parkinson's Disease Questionnaire (PDQ-39) Scores at End of Treatment | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
The PDQ-39 is a self-administered questionnaire that comprises 39 items addressing the following 8 domains of health that patients consider to be adversely affected by the disease:
•Mobility (e.g., fear of falling when walking) - 10 questions;
•Activities of daily living (ADL) - 6 questions;
•Emotional well-being (EMO; e.g., feelings of isolation) - 6 questions;
•Stigma (e.g., social embarrassment) - 4 questions;
•Social support (SOC) - 3 questions;
•Cognition - 4 questions;
•Communication (COM) - 3 questions;
•Bodily discomfort (BOD) - 3 questions.
Each question is answered on a 5-point scale from 0 (Never) to 4 (Always / Cannot Do At All). Domain scores are calculated by summing the answers to the questions in the domain and then converting to a scale from 0 to 100. Higher scores are associated with the more severe symptoms of the disease such as tremor and stiffness. The PDQ-39 summary index includes responses to all 39 items. A negative change indicates improvement.
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End point type |
Secondary
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End point timeframe |
Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
|
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| Notes [19] - 101 subjects had EMO Domain and SOC Domain change from initial LCIG infusion data available |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of LCIG in this study up to 30 days after the date of last PEG-J exposure; median duration of treatment was 1178 days, and maximum was 4217 days (11.5 years).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.0
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Reporting groups
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Reporting group title |
Levodopa-Carbidopa Intestinal Gel
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Reporting group description |
Participants received LCIG continuously administered through a PEG-J directly into the jejunum via a portable pump during 16 hours of wakefulness. Initial dosing was based on the dosing regimen that the participant received during the previous LCIG study. Dosing was individually optimized and adjusted as clinically indicated. In addition to a morning dose (to prime the intestinal tube and rapidly achieve the therapeutic dose level) of 5 to 10 mL (100 to 200 mg levodopa), and the continuous infusion usually 2 to 6 mL/hour (40 to 120 mg levodopa/hour), participants were allowed to self-administer additional doses of LCIG to address immediate subjective needs (eg, deterioration of motor function). Participants received LCIG until it became commercially available. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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28 Oct 2009 |
Amendment 1 implemented the following non-administrative changes:
● The number of study sites has been changed from 20 to 30 to approximately 70 sites. The number of subjects (planned) was changed from approximately 100 to approximately 275 subjects.
● Clarification was made in the inclusion criteria to ensure that enrolled subjects were: (1) completers of Study S187-3-003 or Study S187-3-004, and (2) in the principal investigator's opinion, would continue deriving benefit from long-term LCIG treatment. Clarification was also made in exclusion criteria to exclude those subjects who, in the investigator's opinion, had clinically significant findings (medical, laboratory, psychiatric, or surgical issues) that would interfere with the subject's long-term participation.
● Changed the description of the total daily dose administration. Deleted "bolus" terminology in the morning bolus dose, the continuous maintenance dose, and extra bolus doses given as needed.
● Replacement of PEG-J was changed: Previous device labeling recommended an annual replacement. The new tube labeling no longer required annual replacement. It was to be replaced on the basis of the judgment of the study gastroenterologist and performed as per local practice. A yearly check by the study gastroenterologist was to be included in the schedule of assessments including an evaluation of the tube to ensure the functionality of the tube.
● The list of prohibited medication became less restrictive in recognition of the open-label nature of study treatment and due consideration given to the potential pharmacokinetic and pharmacodynamic interaction with LCIG.
● The efficacy parameters, PD Diary, PDQ-39, and CGI-I, were removed from the clinical study protocol. A routine neurological exam was to be performed every 6 months to assess the continued benefit of LCIG treatment.
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27 Jul 2011 |
Amendment 2 implemented the following non-administrative changes to ensure consistency within the protocol and LCIG program and to provide further clarifications of study design, assessments, and processes:
● Updated inclusion criteria.
● For Canada, subjects who either completed Study S187-3-004 or prematurely discontinued from Study S187-3-004 due to the study ending were allowed to participate in Study S187-3-005 with a minimum of 6 months of exposure to LCIG in Study S187-3-004.
● The laboratory assessments were changed to include markers indicative of vitamin deficiencies that could predispose subjects to polyneuropathy: folic acid, vitamin B6, vitamin B12, MMA, and homocysteine.
● Added a neurological examination.
● Added Laboratory Evaluations table.
● Specified a certified central laboratory, QLAB, to process and provide results for routine clinical laboratory tests throughout the study. Previously, no formal assessment of laboratory evaluations were scheduled, but were done as subject's condition mandated and was performed by a local lab as an element of routine care, and at the time of the subjects' discontinuation of the study.
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20 Mar 2012 |
Amendment 3, dated 20 March 2012, implemented the following non-administrative changes for clarification and alignment with the sponsor's safety assessments:
● Added Post Infusion Night-Time Treatment section.
● Added Oral Rescue Medication section.
● Added C-SSRS assessment.
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17 Dec 2013 |
The purpose of Amendment 4 was to:
● Add language to allow for a legally authorized representative (LAR) to give informed consent if a subject does not have the capacity to provide full informed consent.
● Add language regarding transfer of subjects to commercial product to clarify the assessments that must be performed prior to subjects transferring to commercial product.
● Update clinical device labeling information to clarify that storage conditions are not found on the device labels.
● Update drug and device accountability information to clarify the process of drug and device accountability using the ClinPhone Drug Accountability (CDA) system.
● Update language regarding Adverse Events of Special Interest (AESI) to clarify the use of questionnaires to collect follow-up
information for both serious and nonserious AESIs meeting pre-defined criteria.
● Add the following assessments: Parkinson's Disease Symptom Diary, UPDRS, PDQ-39, Dosing Diary at US sites only to allow for demonstration of maintenance of efficacy.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/29570853 |
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