A 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 (DYSCOVER)
Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT02799381
Collaborator
(none)
63
28
2
31.3
2.3
0.1
Study Details
Study Description
Brief Summary
The primary objective of this 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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This was a Phase 3b, open-label, randomized, multicenter, 12-week study. 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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
63 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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 DYSCOVER (DYSkinesia COmparative Interventional Trial on Duodopa VERsus Oral Medication)
Actual Study Start Date
:
Feb 9, 2017
Actual Primary Completion Date
:
Sep 19, 2019
Actual Study Completion Date
:
Sep 19, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Optimized Medical Treatment (OMT) 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. |
Drug: Optimized antiparkinsonian treatment
Dose levels of prescribed antiparkinsonian medications were individually optimized to their maximum therapeutic effect.
|
| Experimental: Levodopa-Carbidopa Intestinal Gel (LCIG) 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. |
Drug: Levodopa-Carbidopa Intestinal Gel (LCIG)
Dose levels were individually optimized.
Other Names:
Device: CADD-Legacy ambulatory infusion pump
(manufactured by Smiths Medical)
Device: Percutaneous endoscopic gastrostomy tube
(PEG tube)
Device: Jejunal extension tube
(J-tube)
|
Outcome Measures
Primary Outcome Measures
- Mean Change From Baseline to Week 12 in Unified Dyskinesia Rating Scale (UDysRS) Total Score [Baseline, Week 12]
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.
Secondary Outcome Measures
- Mean Change From Baseline to Week 12 in ON Time Without Troublesome Dyskinesia [Baseline, Week 12]
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.
- Mean Change From Baseline to Week 12 in Parkinson's Disease Questionnaire-8 (PDQ-8) Summary Index [Baseline, Week 12]
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.
- Mean Clinical Global Impression of Change (CGI-C) Score at Week 12 [Baseline, Week 12]
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.
- Mean Change From Baseline to Week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score (Activities of Daily Living) [Baseline, Week 12]
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.
- Mean Change From Baseline to Week 12 in OFF Time [Baseline, Week 12]
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.
- Mean Change From Baseline to Week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score (Motor Examination) [Baseline, Week 12]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
30 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Participants must have a diagnosis of idiopathic Parkinson's disease (PD) according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria
-
Participants with advanced levodopa-responsive PD and persistent motor fluctuations who have not been controlled with optimized medical treatment (OMT: the maximum therapeutic effect obtained with pharmacological antiparkinsonian therapies when no further improvement is expected with regard to any additional manipulations of levodopa and/or other antiparkinsonian medication based on the Investigator's clinical judgment)
-
Unified Dyskinesia Rating Scale (UDysRs) Total score ≥ 30 at Visit 3
Exclusion Criteria:
-
Participant(s) treated with levodopa-carbidopa intestinal gel (LCIG) previously
-
Participant's PD diagnosis is unclear or there is a suspicion that the subject has a parkinsonian syndrome such as secondary parkinsonism (e.g. caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), parkinson-plus syndrome (e.g. Multiple System Atrophy, Progressive supranuclear Palsy, Diffuse Lewy Body disease) or other neurodegenerative disease that might mimic the symptoms of PD
-
Participant(s) has undergone neurosurgery for the treatment of Parkinson's disease.
-
Participant(s) has contraindications to levodopa (e.g. narrow angle glaucoma, malignant melanoma)
-
Participant(s) experiencing clinically significant sleep attacks or clinically significant impulsive behavior (e.g. pathological gambling, hypersexuality) at any point during the three months prior to the Screening evaluation as judged by the Principal Investigator
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Parkinson's Disease Treatment Center of Southwest Florida /ID# 150095 | Port Charlotte | Florida | United States | 33980 |
| 2 | Central Texas Neurology Consul /ID# 150088 | Round Rock | Texas | United States | 78681 |
| 3 | Helsinki Univ Central Hospital /ID# 151214 | Helsinki | Finland | 00290 | |
| 4 | Oulun yliopistollinen sairaala /ID# 150947 | Oulu | Finland | 90220 | |
| 5 | Mediterraneo Hospital /ID# 150955 | Glyfada | Greece | 16675 | |
| 6 | University General Hospital of Heraklion "PA.G.N.I" /ID# 150956 | Heraklion | Greece | 71110 | |
| 7 | University Hospital of Ioannin /ID# 150954 | Ioannina | Greece | 45500 | |
| 8 | Pecsi Tudomanyegyetem Klinikai Kozpont I. sz. Belgyogyaszati Klinika /ID# 170116 | Pécs | Pecs | Hungary | 7624 |
| 9 | Semmelweis Egyetem /ID# 170117 | Budapest | Hungary | 1085 | |
| 10 | Szegedi Tudomanyegyetem /ID# 170115 | Szeged | Hungary | 6720 | |
| 11 | Policlinico Universitario Campus Bio-Medico /ID# 150846 | Rome | Lazio | Italy | 00128 |
| 12 | A.O. Univ. Ospedali Riuniti /ID# 150853 | Ancona | Marche | Italy | 60126 |
| 13 | Azienda USL Toscana Centro /ID# 150770 | Florence | Italy | 50012 | |
| 14 | Seconda Universita' di Napoli /ID# 150851 | Naples | Italy | 80138 | |
| 15 | Policlinico Tor Vergata /ID# 151167 | Rome | Italy | 00133 | |
| 16 | Univerzitna nemocnica L. Pasteura /ID# 150146 | Košice - Západ | Kosicky Kraj | Slovakia | 041 66 |
| 17 | Univerzitna nemocnica Martin /ID# 150145 | Martin | Zilinsky Kraj | Slovakia | 036 01 |
| 18 | Univerzitna Nemocnica Bratislava /ID# 150144 | Bratislava | Slovakia | 821 01 | |
| 19 | Univerzitna Nemocnica Bratislava /ID# 150171 | Bratislava | Slovakia | 821 01 | |
| 20 | Hospital Regional Universitari /ID# 171485 | Málaga | Malaga | Spain | 29010 |
| 21 | Hospital Universitario Cruces /ID# 203807 | Barakaldo | Spain | 48903 | |
| 22 | Hospital General Univ de Elche /ID# 150154 | Elche | Spain | 03202 | |
| 23 | Hospital Univ de la Princesa /ID# 150157 | Madrid | Spain | 28006 | |
| 24 | Hospital General Universitario Gregorio Maranon /ID# 150155 | Madrid | Spain | 28007 | |
| 25 | Hospital Univ Ramon y Cajal /ID# 150152 | Madrid | Spain | 28034 | |
| 26 | Hospital Universitario Infanta /ID# 159696 | Madrid | Spain | 28702 | |
| 27 | Hospital Universitario Virgen Macarena /ID# 158861 | Sevilla | Spain | 41009 | |
| 28 | Hospital Virgen de la Salud /ID# 166297 | Toledo | Spain | 45005 |
Sponsors and Collaborators
- AbbVie
Investigators
- Study Director: AbbVie Inc., AbbVie
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT02799381
Other Study ID Numbers:
- M15-535
- 2016-001403-23
First Posted:
Jun 14, 2016
Last Update Posted:
Aug 18, 2020
Last Verified:
Aug 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by AbbVie
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Optimized Medical Treatment (OMT) | Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Arm/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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 33 | 28 |
| COMPLETED | 29 | 25 |
| NOT COMPLETED | 4 | 3 |
Baseline Characteristics
| Arm/Group Title | Optimized Medical Treatment (OMT) | Levodopa-Carbidopa Intestinal Gel (LCIG) | Total |
|---|---|---|---|
| Arm/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. | 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. | Total of all reporting groups |
| Overall Participants | 33 | 28 | 61 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
68.7
(7.20)
|
69.3
(6.99)
|
69.0
(7.05)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
16
48.5%
|
16
57.1%
|
32
52.5%
|
| Male |
17
51.5%
|
12
42.9%
|
29
47.5%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
33
100%
|
28
100%
|
61
100%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Missing |
0
0%
|
0
0%
|
0
0%
|
| Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg/m^2] |
25.2
(4.42)
|
24.5
(4.24)
|
24.9
(4.32)
|
| Parkinson's disease duration (years) (Count of Participants) | |||
| < 10 years |
14
42.4%
|
7
25%
|
21
34.4%
|
| ≥ 10 years |
19
57.6%
|
20
71.4%
|
39
63.9%
|
| Missing |
0
0%
|
1
3.6%
|
1
1.6%
|
Outcome Measures
| Title | Mean Change From Baseline to Week 12 in Unified Dyskinesia Rating Scale (UDysRS) Total Score |
|---|---|
| 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. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: all participants with available data who were randomized to the OMT and all participants who were randomized to LCIG treatment and received at least 1 dose of study drug following PEG-J placement |
| Arm/Group Title | Optimized Medical Treatment (OMT) | Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Arm/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. | 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. |
| Measure Participants | 26 | 24 |
| Least Squares Mean (Standard Error) [units on a scale] |
-2.33
(2.56)
|
-17.37
(2.79)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Optimized Medical Treatment (OMT), Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | 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. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Two-sided p-value | |
| Method | Mixed-effects model repeated measures | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -15.05 | |
| Confidence Interval |
(2-Sided) 95% -21.47 to -8.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Levodopa-Carbidopa Intestinal Gel (LCIG) - Optimized Medical Treatment (OMT) at Week 12 | |
| Title | Mean Change From Baseline to Week 12 in ON Time Without Troublesome Dyskinesia |
|---|---|
| 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. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: all participants with available data who were randomized to the OMT and all participants who were randomized to LCIG treatment and received at least 1 dose of study drug following PEG-J placement |
| Arm/Group Title | Optimized Medical Treatment (OMT) | Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Arm/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. | 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. |
| Measure Participants | 28 | 25 |
| Least Squares Mean (Standard Error) [hours] |
-0.12
(0.63)
|
3.15
(0.69)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Optimized Medical Treatment (OMT), Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | 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. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Two-sided p-value | |
| Method | Mixed-effects model repeated measures | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 3.27 | |
| Confidence Interval |
(2-Sided) 95% 1.71 to 4.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Levodopa-Carbidopa Intestinal Gel (LCIG) - Optimized Medical Treatment (OMT) at Week 12 | |
| Title | Mean Change From Baseline to Week 12 in Parkinson's Disease Questionnaire-8 (PDQ-8) Summary Index |
|---|---|
| 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. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: all participants with available data who were randomized to the OMT and all participants who were randomized to LCIG treatment and received at least 1 dose of study drug following PEG-J placement |
| Arm/Group Title | Optimized Medical Treatment (OMT) | Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Arm/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. | 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. |
| Measure Participants | 29 | 25 |
| Least Squares Mean (Standard Error) [units on a scale] |
-4.95
(3.11)
|
-21.62
(3.47)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Optimized Medical Treatment (OMT), Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | 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. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Two-sided p-value | |
| Method | Mixed-effects model repeated measures | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -16.66 | |
| Confidence Interval |
(2-Sided) 95% -24.48 to -8.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Levodopa-Carbidopa Intestinal Gel (LCIG) - Optimized Medical Treatment (OMT) at Week 12 | |
| Title | Mean Clinical Global Impression of Change (CGI-C) Score at Week 12 |
|---|---|
| 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. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: all participants with available data who were randomized to the OMT and all participants who were randomized to LCIG treatment and received at least 1 dose of study drug following PEG-J placement |
| Arm/Group Title | Optimized Medical Treatment (OMT) | Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Arm/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. | 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. |
| Measure Participants | 32 | 27 |
| Least Squares Mean (Standard Error) [units on a scale] |
4.58
(0.25)
|
2.48
(0.28)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Optimized Medical Treatment (OMT), Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | 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. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Two-sided p-value | |
| Method | Mixed-effects model repeated measures | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.11 | |
| Confidence Interval |
(2-Sided) 95% -2.78 to -1.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Levodopa-Carbidopa Intestinal Gel (LCIG) - Optimized Medical Treatment (OMT) at Week 12 | |
| Title | Mean Change From Baseline to Week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score (Activities of Daily Living) |
|---|---|
| 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. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: all participants with available data who were randomized to the OMT and all participants who were randomized to LCIG treatment and received at least 1 dose of study drug following PEG-J placement |
| Arm/Group Title | Optimized Medical Treatment (OMT) | Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Arm/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. | 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. |
| Measure Participants | 29 | 24 |
| Least Squares Mean (Standard Error) [units on a scale] |
0.21
(1.16)
|
-5.33
(1.28)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Optimized Medical Treatment (OMT), Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | 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. | |
| Statistical Test of Hypothesis | p-Value | =0.0006 |
| Comments | Two-sided p-value | |
| Method | Mixed-effects model repeated measures | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -5.54 | |
| Confidence Interval |
(2-Sided) 95% -8.59 to -2.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Levodopa-Carbidopa Intestinal Gel (LCIG) - Optimized Medical Treatment (OMT) at Week 12 | |
| Title | Mean Change From Baseline to Week 12 in OFF Time |
|---|---|
| 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. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: all participants with available data who were randomized to the OMT and all participants who were randomized to LCIG treatment and received at least 1 dose of study drug following PEG-J placement |
| Arm/Group Title | Optimized Medical Treatment (OMT) | Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Arm/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. | 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. |
| Measure Participants | 28 | 25 |
| Least Squares Mean (Standard Error) [hours] |
0.18
(0.49)
|
-2.17
(0.53)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Optimized Medical Treatment (OMT), Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | 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. | |
| Statistical Test of Hypothesis | p-Value | =0.0002 |
| Comments | Two-sided p-value | |
| Method | Mixed-effects model repeated measures | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.35 | |
| Confidence Interval |
(2-Sided) 95% -3.51 to -1.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Levodopa-Carbidopa Intestinal Gel (LCIG) - Optimized Medical Treatment (OMT) at Week 12 | |
| Title | Mean Change From Baseline to Week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score (Motor Examination) |
|---|---|
| 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. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: all participants with available data who were randomized to the OMT and all participants who were randomized to LCIG treatment and received at least 1 dose of study drug following PEG-J placement |
| Arm/Group Title | Optimized Medical Treatment (OMT) | Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Arm/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. | 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. |
| Measure Participants | 29 | 25 |
| Least Squares Mean (Standard Error) [units on a scale] |
-0.87
(1.89)
|
-4.93
(2.08)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Optimized Medical Treatment (OMT), Levodopa-Carbidopa Intestinal Gel (LCIG) |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | 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. | |
| Statistical Test of Hypothesis | p-Value | =0.0762 |
| Comments | Two-sided p-value | |
| Method | Mixed-effects model repeated measures | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -4.05 | |
| Confidence Interval |
(2-Sided) 95% -8.55 to 0.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Levodopa-Carbidopa Intestinal Gel (LCIG) - Optimized Medical Treatment (OMT) at Week 12 | |
Adverse Events
| Time Frame | Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) collection: OMT (starting after the day of randomization until 30 days after the last visit, up to 18 weeks); LCIG group with study tube removal after the last study drug infusion (from the time of tube placement up to 30 days following tube removal, up to 16 weeks); other LCIG participants (starting with tube placement and up to 30 days following the last study visit, up to 16 weeks) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | TEAEs and SAEs are defined as any adverse event (AE) with an onset date starting after the day of randomization (OMT group) or from the time of tube placement (LCIG group) until 30 days after the last visit (OMT group), or up to 30 days following tube removal (LCIG group) or the last study visit (LCIG group) and were collected whether elicited or spontaneously reported by the participant. | |||
| Arm/Group Title | Levodopa-Carbidopa Intestinal Gel (LCIG) | Optimized Medical Treatment (OMT) | ||
| Arm/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. | 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. | ||
All Cause Mortality |
||||
| Levodopa-Carbidopa Intestinal Gel (LCIG) | Optimized Medical Treatment (OMT) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/28 (0%) | 0/33 (0%) | ||
Serious Adverse Events |
||||
| Levodopa-Carbidopa Intestinal Gel (LCIG) | Optimized Medical Treatment (OMT) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/28 (7.1%) | 0/33 (0%) | ||
| Gastrointestinal disorders | ||||
| PNEUMOPERITONEUM | 1/28 (3.6%) | 1 | 0/33 (0%) | 0 |
| Infections and infestations | ||||
| CYSTITIS | 1/28 (3.6%) | 1 | 0/33 (0%) | 0 |
| Nervous system disorders | ||||
| SYNCOPE | 1/28 (3.6%) | 1 | 0/33 (0%) | 0 |
| Vascular disorders | ||||
| HYPERTENSION | 1/28 (3.6%) | 1 | 0/33 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Levodopa-Carbidopa Intestinal Gel (LCIG) | Optimized Medical Treatment (OMT) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/28 (53.6%) | 4/33 (12.1%) | ||
| Gastrointestinal disorders | ||||
| ABDOMINAL PAIN | 2/28 (7.1%) | 2 | 0/33 (0%) | 0 |
| DIARRHOEA | 2/28 (7.1%) | 2 | 0/33 (0%) | 0 |
| General disorders | ||||
| DRUG WITHDRAWAL SYNDROME | 2/28 (7.1%) | 2 | 0/33 (0%) | 0 |
| Infections and infestations | ||||
| URINARY TRACT INFECTION | 2/28 (7.1%) | 2 | 0/33 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| FALL | 6/28 (21.4%) | 6 | 2/33 (6.1%) | 3 |
| PROCEDURAL PAIN | 3/28 (10.7%) | 3 | 0/33 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| MUSCLE SPASMS | 2/28 (7.1%) | 2 | 0/33 (0%) | 0 |
| Nervous system disorders | ||||
| PARKINSON'S DISEASE | 1/28 (3.6%) | 1 | 2/33 (6.1%) | 2 |
| Psychiatric disorders | ||||
| ANXIETY | 2/28 (7.1%) | 2 | 0/33 (0%) | 0 |
| DEPRESSION | 2/28 (7.1%) | 2 | 1/33 (3%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
| Name/Title | Global Medical Services |
|---|---|
| Organization | AbbVie |
| Phone | 800-633-9110 |
| abbvieclinicaltrials@abbvie.com |
Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT02799381
Other Study ID Numbers:
- M15-535
- 2016-001403-23
First Posted:
Jun 14, 2016
Last Update Posted:
Aug 18, 2020
Last Verified:
Aug 1, 2020