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
Overview
- Phase
- Phase 3
- Intervention
- Levodopa/Carbidopa (LD/CD)
- Conditions
- Parkinson's Disease (PD)
- Sponsor
- AbbVie
- Enrollment
- 174
- Locations
- 76
- Primary Endpoint
- Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "On" Time Without Troublesome Dyskinesia
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
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.
Arms & Interventions
Levodopa/Carbidopa (LD/CD) + Placebo for ABBV-951
After an open-label LD/CD Stabilization Period, participants will receive double-blind oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks
Intervention: Levodopa/Carbidopa (LD/CD)
ABBV-951 + Placebo for Levodopa/Carbidopa (LD/CD)
After an open-label LD/CD Stabilization Period, participants will receive double-blind ABBV-951 by continuous subcutaneous infusion (CSCI) and oral placebo for LD/CD for 12 weeks
Intervention: ABBV-951
ABBV-951 + Placebo for Levodopa/Carbidopa (LD/CD)
After an open-label LD/CD Stabilization Period, participants will receive double-blind ABBV-951 by continuous subcutaneous infusion (CSCI) and oral placebo for LD/CD for 12 weeks
Intervention: Placebo for Levodopa/Carbidopa (LD/CD)
Levodopa/Carbidopa (LD/CD) + Placebo for ABBV-951
After an open-label LD/CD Stabilization Period, participants will receive double-blind oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks
Intervention: Placebo for ABBV-951
Outcomes
Primary Outcomes
Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "On" Time Without Troublesome Dyskinesia
Time Frame: Baseline (Week 0) up to Week 12 of the double-blind treatment period
"On" time is defined as periods of good motor symptom control, and was assessed by the Parkinson's Disease (PD) diary. The normalized "On" time without troublesome dyskinesia is the sum of the normalized "On" time without dyskinesia and the normalized "On" time with non-troublesome dyskinesia. "On" time without dyskinesia plus "On" time with non-troublesome dyskinesia are based on the PD Diary (normalized to a 16-hour waking day averaged over 3 consecutive days). Baseline value is defined as the average of normalized "On" time without troublesome dyskinesia collected over the 3 PD Diary days before randomization.
Secondary Outcomes
- 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(Baseline (Week 0) up to Week 12 of the double-blind treatment period)
- Early Morning "Off" Status (Morning Akinesia) at Week 12 of the Double-Blind Treatment Period(Week 12 of the double-blind treatment period)
- 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(Baseline (Week 0) up to Week 12 of the double-blind treatment period)
- Change From Baseline to Week 12 of the Double-Blind Treatment Period in Median Dyskinesia Score (DK50) as Assessed by the PKG Wearable Device(Baseline (Week 0) up to Week 12 of the double-blind treatment period)
- Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "Off" Time (Hours)(Baseline (Week 0) up to Week 12 of the double-blind treatment period)
- Change From Baseline to Week 12 of the Double-Blind Treatment Period in Parkinson's Disease Sleep Scale-2 (PDSS-2) Total Score(Baseline (Week 0) up to Week 12 of the double-blind treatment period)
- 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(Baseline (Week 0) up to Week 12 of the double-blind treatment period)
- 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(Baseline (Week 0) up to Week 12 of the double-blind treatment period)
- Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "On" Time Without Dyskinesia (Hours)(Baseline, Week 12 of the double-blind treatment period)
- 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(Baseline (Week 0) up to Week 12 of the double-blind treatment period)
- 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(Baseline (Week 0) up to Week 12 of the double-blind treatment period)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Oral LD/CD Stabilization Period(From first dose of stabilization period treatment up to the first dose of the double-blind treatment period)
- Number of Participants With TEAEs During the Double-Blind Treatment Period(From first dose of double-blind treatment up to Week 12 of the double-blind treatment period plus 30 days)
- Number of Participants With Potentially Clinically Significant Changes From Baseline in Hematology, Chemistry, Urinalysis, Special Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs)(Screening up to Week 12 of the double-blind treatment period)
- 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(Baseline (Week 0) up to Week 12 of the double-blind treatment period)
- 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(Day 2 up to Week 12 of the double-blind treatment period plus 30 days)
- 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(Screening up to Week 12 of the double-blind treatment period)