Clinical trial NCT04380142: Study Comparing Continuous Subcutaneous Infusion Of ABBV-951 With Oral Carbidopa/Levodopa Tablets For Treatment Of Motor Fluctuations In Adult Participants With Advanced Parkinson's Disease
Official title: A Randomized, Double-Blind, Double-Dummy, Active-Controlled Study Comparing the Efficacy, Safety and Tolerability of ABBV-951 to Oral Carbidopa/Levodopa in Advanced Parkinson's Disease Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson's Disease (PD)
Keywords: Parkinson's Disease (PD)
ABBV-951
Levodopa/Carbidopa (LD/CD)
Levodopa Phosphate/Carbidopa Phosphate (LDP/CDP)
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-05-08
Enrollment: 174
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Parkinson's disease (PD) is a neurological condition, which affects the brain. PD gets worse over time, but how quickly it progresses varies a lot from person to person. Some symptoms of PD are tremors, stiffness, and slowness of movement. This study measures the efficacy, safety, and tolerability of ABBV-951 versus oral Levodopa (LD)/Carbidopa (CD) \[LD/CD\] in advanced PD participants to achieve reduction in motor fluctuations.

ABBV-951 is an investigational (unapproved) drug containing Levodopa Phosphate/Carbidopa Phosphate (LDP/CDP) given subcutaneously (under the skin) for the treatment of Parkinson's Disease. Adult participants with advanced PD will be enrolled. Approximately 130 participants will be enrolled in the study in approximately 80 sites across the world.

In one arm, participants will receive ABBV-951 solution as a continuous infusion under the skin plus oral placebo capsules for LD/CD. In the second arm, participants will receive placebo solution for ABBV-951 as a continuous infusion under the skin plus oral capsules containing LD/CD tablets. The treatment duration is 12 weeks.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects, and completing questionnaires.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of idiopathic Parkinson's Disease (PD) that is levodopa-responsive.
* Participant must be taking a minimum of 400 milligrams/day (mg/day) of Levodopa (LD) equivalents and be judged by the investigator to have motor symptoms inadequately controlled by current therapy, have a recognizable/identifiable "Off" and "On" states (motor fluctuations), and have an average "Off" time of at least 2.5 hours/day over 3 consecutive PD Diary days with a minimum of 2 hours each day.
* Participant or caregiver, if applicable, demonstrates the understanding and correct use of the delivery system, including the insertion of the cannula into the participant's abdomen, as assessed by the investigator or designee during the Screening period.

Exclusion Criteria:

* Clinically significant, unstable medical conditions or any other reason that the investigator determines would interfere with the participant's participation in this study or would make the participant an unsuitable candidate to receive study drug.
* History of allergic reaction or significant sensitivity to LD or constituents of the study drug (and its excipients) and/or other products in the same class.
* Participant has not received deep brain stimulation, CD/LD enteral suspension, or any other PD medication as continuous daily infusion, whether commercially available or investigational. Previous exposure to ABBV-951 is not allowed.

Primary outcomes:
measure: Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "On" Time Without Troublesome Dyskinesia
timeFrame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
Secondary outcomes:
measure: Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "Off" Time (Hours)
timeFrame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
measure: Change From Baseline to Week 12 of the Double-Blind Treatment Period in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II Score
timeFrame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
measure: Early Morning "Off" Status (Morning Akinesia) at Week 12 of the Double-Blind Treatment Period
timeFrame: Week 12 of the double-blind treatment period
measure: Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "On" Time Without Dyskinesia (Hours)
timeFrame: Baseline, Week 12 of the double-blind treatment period
measure: Change From Baseline to Week 12 of the Double-Blind Treatment Period in Parkinson's Disease Sleep Scale-2 (PDSS-2) Total Score
timeFrame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
measure: Change From Baseline to Week 12 of the Double-Blind Treatment Period in Quality of Life Assessed by Parkinson's Disease Questionnaire 39 Item (PDQ-39) Summary Index Score
timeFrame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
measure: Change From Baseline to Week 12 of the Double-Blind Treatment Period in Quality of Life Assessed by the EuroQol 5-Dimension Questionnaire (EQ-5D-5L) Summary Index
timeFrame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
measure: Change From Baseline to Week 12 of the Double-Blind Treatment Period in Median Bradykinesia Score (BK50) as Assessed by the Parkinson's KinetiGraph/Personal KinetiGraph (PKG) Wearable Device
timeFrame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
measure: Change From Baseline to Week 12 of the Double-Blind Treatment Period in Interquartile Range of Bradykinesia Score (BK75-BK25) as Assessed by the PKG Wearable Device
timeFrame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
measure: Change From Baseline to Week 12 of the Double-Blind Treatment Period in Median Dyskinesia Score (DK50) as Assessed by the PKG Wearable Device
timeFrame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
measure: Change From Baseline to Week 12 of the Double-Blind Treatment Period in Interquartile Range of Dyskinesia Score (DK75-DK25) as Assessed by the PKG Wearable Device
timeFrame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
measure: Number of Participants With Irritation Grade Numeric Grade >= 5 or Letter Grade >= D on the Infusion Site Irritation Scale Across All Study Post-Baseline Visits
timeFrame: Day 2 up to Week 12 of the double-blind treatment period plus 30 days
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Oral LD/CD Stabilization Period
timeFrame: From first dose of stabilization period treatment up to the first dose of the double-blind treatment period
measure: Number of Participants With TEAEs During the Double-Blind Treatment Period
timeFrame: From first dose of double-blind treatment up to Week 12 of the double-blind treatment period plus 30 days
measure: Number of Participants With Potentially Clinically Significant Changes From Baseline in Hematology, Chemistry, Urinalysis, Special Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs)
timeFrame: Screening up to Week 12 of the double-blind treatment period
measure: Number of Participants With Affirmative Responses on the Columbia-Suicide Severity Rating Scale (C-SSRS) Across All Study Post-Baseline Visits During the Double-Blind Treatment Period
timeFrame: Screening up to Week 12 of the double-blind treatment period
measure: Number of Participants With a Subscore > 5 For Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Ration Scale (QUIP-RS) at Any Time During the Double-Blind Treatment Period
timeFrame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - Main /ID# 216595
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama /ID# 216757
state: Alabama
city: Phoenix
country: United States
facility: Xenoscience, Inc /ID# 217110
state: Arizona
city: Phoenix
country: United States
facility: Barrow Neurological Institute /ID# 216566
state: Arizona
city: Phoenix
country: United States
facility: HonorHealth /ID# 216642
state: Arizona
city: Scottsdale
country: United States
facility: Movement Disorders Center of Arizona /ID# 216503
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Res Inst /ID# 216507
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences /ID# 216501
state: Arkansas
city: Fountain Valley
country: United States
facility: The Parkinson's & Movement Disorder Institute - Fountain Valley /ID# 216705
state: California
city: Fresno
country: United States
facility: Neuro Pain Medical Center /ID# 216551
state: California
city: La Jolla
country: United States
facility: University of California, San /ID# 216598
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical /ID# 216500
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Research - Long Beach /ID# 216970
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles /ID# 216674
state: California
city: Pasadena
country: United States
facility: SC3 Research Group - Pasadena /ID# 216821
state: California
city: West Hollywood
country: United States
facility: Cedars-Sinai Medical Center-West Hollywood /ID# 216561
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital /ID# 216527
state: Colorado
city: Boulder
country: United States
facility: Alpine Clinical Research Center /ID# 216637
state: Colorado
city: Denver
country: United States
facility: Denver Neurological Research, LLC /ID# 216784
state: Colorado
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorders Center /ID# 216737
state: Colorado
city: Newark
country: United States
facility: Christiana Care Health Service /ID# 216515
state: Delaware
city: Washington
country: United States
facility: Georgetown University Hospital /ID# 216632
state: District of Columbia
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton /ID# 216517
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research /ID# 217089
state: Florida
city: Gainesville
country: United States
facility: Fixel Institute for Neurological Diseases /ID# 216514
state: Florida
city: Miami
country: United States
facility: Visionary Investigators Network - Miami /ID# 216679
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research /ID# 216765
state: Florida
city: Ormond Beach
country: United States
facility: Neurology Associates Ormond Beach /ID# 216521
state: Florida
city: Port Charlotte
country: United States
facility: Parkinson's Disease Treatment Center of Southwest Florida /ID# 222656
state: Florida
city: Tampa
country: United States
facility: University of South Florida /ID# 216638
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute - Palm Beach /ID# 217207
state: Florida
city: Atlanta
country: United States
facility: Duplicate_Atlanta Center for Medical Res /ID# 217091
state: Georgia
city: Gainesville
country: United States
facility: The Neurological Center of North Georgia /ID# 216499
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center /ID# 216567
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical /ID# 217187
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Clinical Research Cent /ID# 216615
state: Indiana
city: Kansas City
country: United States
facility: Univ Kansas Med Ctr /ID# 216528
state: Kansas
city: Brighton
country: United States
facility: St Elizabeth's Medical Center - Brighton /ID# 216716
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University /ID# 217158
state: Michigan
city: Chesterfield
country: United States
facility: Clinical Research Professionals - Chesterfield /ID# 216669
state: Missouri
city: Kansas City
country: United States
facility: St. Luke's Hosp. of Kansas City /ID# 216633
state: Missouri
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 216548
state: Missouri
city: Lawrenceville
country: United States
facility: Global Neurosciences Institute /ID# 217875
state: New Jersey
city: Lake Success
country: United States
facility: Northwell Health /ID# 216833
state: New York
city: New York
country: United States
facility: Mount Sinai Beth Israel /ID# 216712
state: New York
city: Rochester
country: United States
facility: University of Rochester /ID# 218737
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Univ HS /ID# 216522
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University - Wexner Medical Center /ID# 216900
state: Ohio
city: New Albany
country: United States
facility: The Orthopedic Foundation /ID# 217157
state: Ohio
city: Tulsa
country: United States
facility: The Movement Disorder Clinic of Oklahoma /ID# 216860
state: Oklahoma
city: Portland
country: United States
facility: Legacy Research Institute /ID# 216558
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania /ID# 216560
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital /ID# 216553
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health-Upstate /ID# 216594
state: South Carolina
city: Greer
country: United States
facility: Premier Neurology, P.C. /ID# 217308
state: South Carolina
city: Port Royal
country: United States
facility: Coastal Neurology /ID# 217190
state: South Carolina
city: Franklin
country: United States
facility: KCA Neurology - Franklin /ID# 217419
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center /ID# 216675
state: Tennessee
city: Cypress
country: United States
facility: Houston Pulmonary Sleep and Allergy Associates /ID# 216942
state: Texas
city: Dallas
country: United States
facility: Kerwin Research Center /ID# 216587
state: Texas
city: Dallas
country: United States
facility: Neurology Consultants of Dallas - LBJ Fwy /ID# 216564
state: Texas
city: Georgetown
country: United States
facility: Texas Movement Disorder Specialists /ID# 216523
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital /ID# 216707
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consul /ID# 216629
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Care /ID# 216710
state: Utah
city: Norfolk
country: United States
facility: Meridian Clinical Research /ID# 216731
state: Virginia
city: Richmond
country: United States
facility: Neurological Associates - Forest Ave /ID# 216636
state: Virginia
city: Seattle
country: United States
facility: Swedish Neuroscience /ID# 216526
state: Washington
city: Spokane
country: United States
facility: Inland Northwest Research /ID# 221036
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin /ID# 216498
state: Wisconsin
city: Liverpool
country: Australia
facility: Liverpool Hospital /ID# 218681
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital /ID# 216535
state: New South Wales
city: SouthPort
country: Australia
facility: Gold coast University Hospital /ID# 218373
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital /ID# 216533
state: South Australia
city: Cheltenham
country: Australia
facility: Kingston Centre /ID# 216537
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital /ID# 216536
state: Victoria
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: Soileau MJ, Aldred J, Budur K, Fisseha N, Fung VS, Jeong A, Kimber TE, Klos K, Litvan I, O'Neill D, Robieson WZ, Spindler MA, Standaert DG, Talapala S, Vaou EO, Zheng H, Facheris MF, Hauser RA. Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial. Lancet Neurol. 2022 Dec;21(12):1099-1109. doi: 10.1016/S1474-4422(22)00400-8.