Clinical Trial Results:
An Open-label, Randomized 12 Week Study Comparing Efficacy of Levodopa-Carbidopa Intestinal Gel/Carbidopa-Levodopa Enteral Suspension and Optimized Medical Treatment on Dyskinesia in Subjects with Advanced Parkinson's Disease
Summary
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EudraCT number |
2016-001403-23 |
Trial protocol |
FI SK GR ES HU IT |
Global end of trial date |
19 Sep 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Sep 2020
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First version publication date |
03 Sep 2020
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Other versions |
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 |
M15-535
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02799381 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
AbbVie
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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 |
AbbVie, Global Medical Services, 001 8006339110, abbvieclinicaltrials@abbvie.com
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Scientific contact |
AbbVie, Global Medical Services, 001 8006339110, 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 |
19 Sep 2019
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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 |
19 Sep 2019
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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 Phase 3b, open-label, randomized, multicenter, 12-week study was to examine the effect of levodopa-carbidopa intestinal gel (LCIG) compared with optimized medical treatment (OMT) on dyskinesia in participants with advanced Parkinson's disease (PD). The study consisted of 3 sequential periods: Screening, Treatment, and Follow-Up. The OMT group had the same schedule of visits/procedures throughout the study as the LCIG treatment group, except for visits related to nasojejunal (NJ)/percutaneous endoscopic gastrostomy (PEG) procedures, titration of LCIG, and follow-up period.
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Protection of trial subjects |
Subject and/or legal guardian 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 |
09 Feb 2017
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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 |
Finland: 6
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Country: Number of subjects enrolled |
Greece: 7
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Country: Number of subjects enrolled |
Hungary: 6
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Country: Number of subjects enrolled |
Italy: 13
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Country: Number of subjects enrolled |
Slovakia: 12
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Country: Number of subjects enrolled |
Spain: 18
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Country: Number of subjects enrolled |
United States: 1
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Worldwide total number of subjects |
63
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EEA total number of subjects |
62
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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) |
10
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From 65 to 84 years |
53
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||
Pre-assignment
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Screening details |
Safety Data Set: all participants randomized to OMT and all participants randomized to LCIG treatment who had a study tube (NJ or PEG-J) placement procedure. Two participants randomized to the LCIG arm did not have device placement for LCIG infusion and were not included in the safety data set. | |||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Optimized Medical Treatment (OMT) | |||||||||||||||||||||
Arm description |
Participants randomized to OMT continued their current anti Parkinson’s disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT. | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Optimized antiparkinsonian treatment
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, Tablet, Transdermal patch
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Routes of administration |
Oral use, Transdermal use
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Dosage and administration details |
Dose levels of prescribed antiparkinsonian medications were individually optimized to their maximum therapeutic effect.
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Arm title
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Levodopa-Carbidopa Intestinal Gel (LCIG) | |||||||||||||||||||||
Arm description |
The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant’s response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Levodopa-Carbidopa Intestinal Gel (LCIG)
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Investigational medicinal product code |
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Other name |
ABT-SLV187, DUOPA (carbidopa and levodopa Enteral Suspension), DUODOPA
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Pharmaceutical forms |
Concentrate and solvent for solution for infusion
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Routes of administration |
Intestinal use
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Dosage and administration details |
Dose levels were individually optimized.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Two participants randomized to the LCIG arm did not have device placement for LCIG infusion and were not included in the safety data set. |
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Baseline characteristics reporting groups
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Reporting group title |
Optimized Medical Treatment (OMT)
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Reporting group description |
Participants randomized to OMT continued their current anti Parkinson’s disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Levodopa-Carbidopa Intestinal Gel (LCIG)
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Reporting group description |
The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant’s response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Optimized Medical Treatment (OMT)
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Reporting group description |
Participants randomized to OMT continued their current anti Parkinson’s disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT. | ||
Reporting group title |
Levodopa-Carbidopa Intestinal Gel (LCIG)
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Reporting group description |
The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant’s response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day. |
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End point title |
Mean Change from Baseline to Week 12 in Unified Dyskinesia Rating Scale (UDysRS) Total Score | ||||||||||||
End point description |
The Unified Dyskinesia Rating Scale (UDysRS) is a tool used to assess dyskinesia in Parkinson’s disease (PD) and contains both self-evaluation questions and items that are assessed directly by the physician to objectively rate the abnormal movements associated with PD. Part 1 contains 11 questions about the ON time dyskinesia and the impact of ON-dyskinesia on experiences of daily living. Part 2 contains 4 questions about OFF-dystonia rating. Part 3 contains 7 questions about objective evaluation of dyskinesia impairment and Part 4 contains 4 questions regarding dyskinesia disability. Each question is scored with respect to severity, which is rated on a scale where 0 = normal, 1 = slight, 2 = mild, 3= moderate and 4 = severe. The UDysRS total score is obtained by summing the item scores, ranging from 0 to 104. Higher scores are associated with more disability. Negative changes from baseline indicate improvement.
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End point type |
Primary
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End point timeframe |
Baseline, Week 12
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Notes [1] - Intent-to-treat (ITT): subjects with available data at Wk 12 who were randomized to the OMT group [2] - ITT: randomized w/available data at Wk 12 who rcvd ≥ 1 dose of study drug after PEG-J placement |
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Statistical analysis title |
Change from baseline to Week 12 | ||||||||||||
Statistical analysis description |
The likelihood-based mixed-effects model repeated measures (MMRM) analysis of the change from baseline to Week 12 used all observed data. The model included fixed, categorical effects for treatment, country, visit, and treatment-by-visit interaction, with continuous fixed covariates for baseline score and the baseline score-by-visit interaction.
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Comparison groups |
Optimized Medical Treatment (OMT) v Levodopa-Carbidopa Intestinal Gel (LCIG)
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Number of subjects included in analysis |
50
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [3] | ||||||||||||
Method |
Mixed-effects model repeated measures | ||||||||||||
Parameter type |
LS Mean Difference (LCIG-OMT) at Week 12 | ||||||||||||
Point estimate |
-15.05
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-21.47 | ||||||||||||
upper limit |
-8.63 | ||||||||||||
Notes [3] - Two-sided p-value |
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End point title |
Mean Change from Baseline to Week 12 in ON time without troublesome dyskinesia | ||||||||||||
End point description |
The Parkinson’s Disease (PD) Symptom Diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected study 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. ON time is when PD symptoms are well controlled by the drug, and OFF time is when PD symptoms are not adequately controlled by the drug. Positive change from baseline for ON time without troublesome dyskinesia indicates improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Notes [4] - Intent-to-treat (ITT): subjects with available data at Wk 12 who were randomized to the OMT group [5] - ITT: randomized w/available data at Wk 12 who rcvd ≥ 1 dose of study drug after PEG-J placement |
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Statistical analysis title |
Change from baseline to Week 12 | ||||||||||||
Statistical analysis description |
If the primary efficacy variable was statistically significant, each of the secondary variables were to be tested using a fixed sequence as a gatekeeping procedure and at α level of 0.050. Testing was to cease at the point that a secondary variable failed to demonstrate statistical significance.
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Comparison groups |
Optimized Medical Treatment (OMT) v Levodopa-Carbidopa Intestinal Gel (LCIG)
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Number of subjects included in analysis |
53
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Analysis specification |
Pre-specified
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Analysis type |
superiority [6] | ||||||||||||
P-value |
< 0.0001 [7] | ||||||||||||
Method |
Mixed-effects model repeated measures | ||||||||||||
Parameter type |
LS Mean Difference (LCIG-OMT) at Week 12 | ||||||||||||
Point estimate |
3.27
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.71 | ||||||||||||
upper limit |
4.83 | ||||||||||||
Notes [6] - The likelihood-based mixed-effects model repeated measures (MMRM) analysis of the change from baseline to Week 12 used all observed data. The model included fixed, categorical effects for treatment, country, visit, and treatment-by-visit interaction, with continuous fixed covariates for baseline score and the baseline score-by-visit interaction. [7] - Two-sided p-value |
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End point title |
Mean Change from Baseline to Week 12 in Parkinson's Disease Questionnaire-8 (PDQ-8) Summary Index | ||||||||||||
End point description |
The Parkinson's Disease Questionnaire-8 (PDQ-8) is a disease-specific instrument designed to measure aspects of health that are relevant to participants with PD, and which may not be included in general health status questionnaires. The PDQ-8 is a self-administered questionnaire. 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). Higher scores are consistently associated with the more severe symptoms of the disease such as tremors and stiffness. The results are presented as a summary index. The PDQ-8 summary index ranges from 0 to 100, where lower scores indicate a better perceived health status. Negative changes from baseline indicate improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Notes [8] - Intent-to-treat (ITT): subjects with available data at Wk 12 who were randomized to the OMT group [9] - ITT: randomized w/available data at Wk 12 who rcvd ≥ 1 dose of study drug after PEG-J placement |
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Statistical analysis title |
Change from baseline to Week 12 | ||||||||||||
Statistical analysis description |
If the primary efficacy variable was statistically significant, each of the secondary variables were to be tested using a fixed sequence as a gatekeeping procedure and at α level of 0.050. Testing was to cease at the point that a secondary variable failed to demonstrate statistical significance.
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Comparison groups |
Optimized Medical Treatment (OMT) v Levodopa-Carbidopa Intestinal Gel (LCIG)
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Number of subjects included in analysis |
54
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Analysis specification |
Pre-specified
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Analysis type |
superiority [10] | ||||||||||||
P-value |
< 0.0001 [11] | ||||||||||||
Method |
Mixed-effects model repeated measures | ||||||||||||
Parameter type |
LS Mean Difference (LCIG-OMT) at Week 12 | ||||||||||||
Point estimate |
-16.66
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-24.48 | ||||||||||||
upper limit |
-8.85 | ||||||||||||
Notes [10] - The likelihood-based mixed-effects model repeated measures (MMRM) analysis of the change from baseline to Week 12 used all observed data. The model included fixed, categorical effects for treatment, country, visit, and treatment-by-visit interaction, with continuous fixed covariates for baseline score and the baseline score-by-visit interaction. [11] - Two-sided p-value |
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End point title |
Mean Clinical Global Impression of Change (CGI-C) Score at Week 12 | ||||||||||||
End point description |
The Clinical Global Impression of Change (CGI-C) score is a clinician's rating scale for assessing Global Improvement of Change. The CGI-C rates improvement by 7 categories: very much improved (1), much improved (2), minimally improved (3), no change (4), minimally worse (5), much worse (6), very much worse (7). The CGI-C score ranges from 1 to 7, with lower scores indicating improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Notes [12] - Intent-to-treat (ITT): subjects with available data at Wk 12 who were randomized to the OMT group [13] - ITT: randomized w/available data at Wk 12 who rcvd ≥ 1 dose of study drug after PEG-J placement |
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Statistical analysis title |
CGI-C Score at Week 12 | ||||||||||||
Statistical analysis description |
If the primary efficacy variable was statistically significant, each of the secondary variables were to be tested using a fixed sequence as a gatekeeping procedure and at α level of 0.050. Testing was to cease at the point that a secondary variable failed to demonstrate statistical significance.
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Comparison groups |
Optimized Medical Treatment (OMT) v Levodopa-Carbidopa Intestinal Gel (LCIG)
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Number of subjects included in analysis |
54
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Analysis specification |
Pre-specified
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Analysis type |
superiority [14] | ||||||||||||
P-value |
< 0.0001 [15] | ||||||||||||
Method |
Mixed-effects model repeated measures | ||||||||||||
Parameter type |
LS Mean Difference (LCIG-OMT) at Week 12 | ||||||||||||
Point estimate |
-2.11
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-2.78 | ||||||||||||
upper limit |
-1.44 | ||||||||||||
Notes [14] - The likelihood-based mixed-effects model repeated measures (MMRM) analysis of the change from baseline to Week 12 used all observed data. The model included fixed, categorical effects for treatment, country, visit, and treatment-by-visit interaction, with continuous fixed covariates for baseline score and the baseline score-by-visit interaction. [15] - Two-sided p-value |
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End point title |
Mean Change From Baseline to Week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score (Activities of Daily Living) | ||||||||||||
End point description |
The Unified Parkinson's Disease Rating Scale (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 related to Activities of Daily Living, and ranges from 0-52. Higher scores are associated with more disability. Negative values indicate improvement from baseline.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Notes [16] - Intent-to-treat (ITT): subjects with available data at Wk 12 who were randomized to the OMT group [17] - ITT: randomized w/available data at Wk 12 who rcvd ≥ 1 dose of study drug after PEG-J placement |
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Statistical analysis title |
Change from baseline to Week 12 | ||||||||||||
Statistical analysis description |
If the primary efficacy variable was statistically significant, each of the secondary variables were to be tested using a fixed sequence as a gatekeeping procedure and at α level of 0.050. Testing was to cease at the point that a secondary variable failed to demonstrate statistical significance.
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Comparison groups |
Optimized Medical Treatment (OMT) v Levodopa-Carbidopa Intestinal Gel (LCIG)
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Number of subjects included in analysis |
53
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Analysis specification |
Pre-specified
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Analysis type |
superiority [18] | ||||||||||||
P-value |
= 0.0006 [19] | ||||||||||||
Method |
Mixed-effects model repeated measures | ||||||||||||
Parameter type |
LS Mean Difference (LCIG-OMT) at Week 12 | ||||||||||||
Point estimate |
-5.54
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-8.59 | ||||||||||||
upper limit |
-2.49 | ||||||||||||
Notes [18] - The likelihood-based mixed-effects model repeated measures (MMRM) analysis of the change from baseline to Week 12 used all observed data. The model included fixed, categorical effects for treatment, country, visit, and treatment-by-visit interaction, with continuous fixed covariates for baseline score and the baseline score-by-visit interaction. [19] - Two-sided p-value |
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End point title |
Mean Change from Baseline to Week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score (Motor Examination) | ||||||||||||
End point description |
The Unified Parkinson's Disease Rating Scale (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 related to Motor Examination, and ranges from 0-108. Higher scores are associated with more disability. Negative values indicate improvement from baseline.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Notes [20] - Intent-to-treat (ITT): subjects with available data at Wk 12 who were randomized to the OMT group [21] - ITT: randomized w/available data at Wk 12 who rcvd ≥ 1 dose of study drug after PEG-J placement |
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Statistical analysis title |
Change from baseline to Week 12 | ||||||||||||
Statistical analysis description |
If the primary efficacy variable was statistically significant, each of the secondary variables were to be tested using a fixed sequence as a gatekeeping procedure and at α level of 0.050. Testing was to cease at the point that a secondary variable failed to demonstrate statistical significance.
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Comparison groups |
Optimized Medical Treatment (OMT) v Levodopa-Carbidopa Intestinal Gel (LCIG)
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Number of subjects included in analysis |
54
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Analysis specification |
Pre-specified
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Analysis type |
superiority [22] | ||||||||||||
P-value |
= 0.0762 [23] | ||||||||||||
Method |
Mixed-effects model repeated measures | ||||||||||||
Parameter type |
LS Mean Difference (LCIG-OMT) at Week 12 | ||||||||||||
Point estimate |
-4.05
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-8.55 | ||||||||||||
upper limit |
0.44 | ||||||||||||
Notes [22] - The likelihood-based mixed-effects model repeated measures (MMRM) analysis of the change from baseline to Week 12 used all observed data. The model included fixed, categorical effects for treatment, country, visit, and treatment-by-visit interaction, with continuous fixed covariates for baseline score and the baseline score-by-visit interaction. [23] - Two-sided p-value |
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End point title |
Mean Change from Baseline to Week 12 in OFF time | ||||||||||||
End point description |
The Parkinson’s Disease (PD) Symptom Diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected study 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. ON time is when PD symptoms are well controlled by the drug, and OFF time is when PD symptoms are not adequately controlled by the drug. Negative change from baseline for OFF time indicates improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Notes [24] - Intent-to-treat (ITT): subjects with available data at Wk 12 who were randomized to the OMT group [25] - ITT: randomized w/available data at Wk 12 who rcvd ≥ 1 dose of study drug after PEG-J placement |
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Statistical analysis title |
Change from baseline to Week 12 | ||||||||||||
Statistical analysis description |
If the primary efficacy variable was statistically significant, each of the secondary variables were to be tested using a fixed sequence as a gatekeeping procedure and at α level of 0.050. Testing was to cease at the point that a secondary variable failed to demonstrate statistical significance.
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Comparison groups |
Optimized Medical Treatment (OMT) v Levodopa-Carbidopa Intestinal Gel (LCIG)
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Number of subjects included in analysis |
53
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Analysis specification |
Pre-specified
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Analysis type |
superiority [26] | ||||||||||||
P-value |
= 0.0002 [27] | ||||||||||||
Method |
Mixed-effects model repeated measures | ||||||||||||
Parameter type |
LS Mean Difference (LCIG-OMT) at Week 12 | ||||||||||||
Point estimate |
-2.35
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-3.51 | ||||||||||||
upper limit |
-1.19 | ||||||||||||
Notes [26] - The likelihood-based mixed-effects model repeated measures (MMRM) analysis of the change from baseline to Week 12 used all observed data. The model included fixed, categorical effects for treatment, country, visit, and treatment-by-visit interaction, with continuous fixed covariates for baseline score and the baseline score-by-visit interaction. [27] - Two-sided p-value |
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Adverse events information
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Timeframe for reporting adverse events |
TEAEs /TESAEs: OMT after randomization until 30 d after last visit, ≤ 18 wks; LCIG study tubes removed after last Tx, from tube placement up to 30 d after tube removal, ≤ 16 wks; other LCIG: from tube placement up to 30 d after last study visit, ≤ 16 wks
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Adverse event reporting additional description |
TEAEs and SAEs are defined as any adverse event (AE) with onset date after the day of randomization (OMT group) or from time of tube placement (LCIG group) until 30 d after the last visit (OMT group), or up to 30 d following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.0
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Reporting groups
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Reporting group title |
Levodopa-Carbidopa Intestinal Gel (LCIG)
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Reporting group description |
The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant’s response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Optimized Medical Treatment (OMT)
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Reporting group description |
Participants randomized to OMT continued their current anti Parkinson’s disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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26 May 2016 |
● Changed the study duration from 26 weeks to 12 weeks
● Removed the exclusion criterion for excluding patients previously treated with continuous subcutaneous apomorphine infusion
● Added language for additional analysis to provide evidence on the construct validity of the UDysRS
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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 |