Trial Outcomes & Findings for 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 (NCT NCT04380142)

Results Overview

"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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

174 participants

Primary outcome timeframe

Baseline (Week 0) up to Week 12 of the double-blind treatment period

Results posted on

2022-11-18

Participant Flow

Enrolled participants entered an open-label oral Levodopa/Carbidopa (LD/CD) Stabilization Period of 14 to 21 days, at the end of which, eligible participants were randomized 1:1 to 12 weeks of treatment with either: 24-hour/day continuous subcutaneous infusion (CSCI) of ABBV-951 + oral placebo capsules for LD/CD immediate-release (IR) or 24-hour/day CSCI of placebo solution for ABBV-951 + encapsulated LD/CD IR tablets in a 12-week Double-Blind Treatment Period.

Participant milestones

Participant milestones
Measure	LD/CD Stabilization Period The dose and schedule of oral LD/CD were adjusted over the first 7 to 14 days by the investigator to achieve the best possible control of the participant's motor symptoms; that included using nighttime dosing if needed and was agreed upon by the participant and the investigator. Once stabilized, no further adjustments to oral LD/CD IR were to be made for at least 7 days prior to randomization.	LD/CD + Placebo for ABBV-951 Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
LD/CD Stabilization Period STARTED	174	0	0
LD/CD Stabilization Period COMPLETED	145	0	0
LD/CD Stabilization Period NOT COMPLETED	29	0	0
Double-Blind Treatment Period STARTED	0	69	76
Double-Blind Treatment Period Randomized and Treated	0	67	74
Double-Blind Treatment Period COMPLETED	0	62	48
Double-Blind Treatment Period NOT COMPLETED	0	7	28

Reasons for withdrawal

Reasons for withdrawal
Measure	LD/CD Stabilization Period The dose and schedule of oral LD/CD were adjusted over the first 7 to 14 days by the investigator to achieve the best possible control of the participant's motor symptoms; that included using nighttime dosing if needed and was agreed upon by the participant and the investigator. Once stabilized, no further adjustments to oral LD/CD IR were to be made for at least 7 days prior to randomization.	LD/CD + Placebo for ABBV-951 Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
LD/CD Stabilization Period Adverse Event	3	0	0
LD/CD Stabilization Period Withdrawal by Subject	4	0	0
LD/CD Stabilization Period Lost to Follow-up	1	0	0
LD/CD Stabilization Period Lack of Efficacy	1	0	0
LD/CD Stabilization Period Difficulty With Drug Delivery System	2	0	0
LD/CD Stabilization Period Other, Not Specified	18	0	0
Double-Blind Treatment Period Adverse Event	0	1	14
Double-Blind Treatment Period Withdrew Consent	0	3	6
Double-Blind Treatment Period Lack of Efficacy	0	0	2
Double-Blind Treatment Period Difficulty With Drug Delivery System	0	1	3
Double-Blind Treatment Period Other, Not Specified	0	0	1
Double-Blind Treatment Period Did Not Receive Study Drug	0	2	2

Baseline Characteristics

Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LD/CD + Placebo for ABBV-951 n=67 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=74 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.	Total n=141 Participants Total of all reporting groups
Age, Continuous	66.6 years STANDARD_DEVIATION 9.82 • n=67 Participants	66.3 years STANDARD_DEVIATION 9.20 • n=74 Participants	66.4 years STANDARD_DEVIATION 9.47 • n=141 Participants
Sex: Female, Male Female	18 Participants n=67 Participants	24 Participants n=74 Participants	42 Participants n=141 Participants
Sex: Female, Male Male	49 Participants n=67 Participants	50 Participants n=74 Participants	99 Participants n=141 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=67 Participants	4 Participants n=74 Participants	5 Participants n=141 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	66 Participants n=67 Participants	70 Participants n=74 Participants	136 Participants n=141 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=67 Participants	0 Participants n=74 Participants	0 Participants n=141 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=67 Participants	1 Participants n=74 Participants	1 Participants n=141 Participants
Race (NIH/OMB) Asian	3 Participants n=67 Participants	0 Participants n=74 Participants	3 Participants n=141 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=67 Participants	1 Participants n=74 Participants	2 Participants n=141 Participants
Race (NIH/OMB) Black or African American	2 Participants n=67 Participants	2 Participants n=74 Participants	4 Participants n=141 Participants
Race (NIH/OMB) White	61 Participants n=67 Participants	70 Participants n=74 Participants	131 Participants n=141 Participants
Race (NIH/OMB) More than one race	0 Participants n=67 Participants	0 Participants n=74 Participants	0 Participants n=141 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=67 Participants	0 Participants n=74 Participants	0 Participants n=141 Participants
Averaged Normalized On Time Without Troublesome Dyskinesia	9.49 normalized hours STANDARD_DEVIATION 2.619 • n=67 Participants • Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment.	9.20 normalized hours STANDARD_DEVIATION 2.423 • n=73 Participants • Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment.	9.34 normalized hours STANDARD_DEVIATION 2.514 • n=140 Participants • Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment.

PRIMARY outcome

Timeframe: Baseline (Week 0) up to Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with a baseline and Week 12 assessment.

"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.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=62 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=47 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "On" Time Without Troublesome Dyskinesia	0.97 hours Standard Error 0.50	2.72 hours Standard Error 0.52

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with a baseline and Week 12 assessment.

"Off" time is defined as periods of poor mobility, tremor, slowness, and stiffness and was assessed by the PD Diary.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=62 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=47 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "Off" Time (Hours)	-0.96 hours Standard Error 0.49	-2.75 hours Standard Error 0.50

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with a baseline and Week 12 assessment.

The Part II MDS-UPDRS is an investigator-used rating tool to follow the longitudinal course of PD. MDS-UPDRS is multimodal scale assessing impairment and disability. Part II assesses the participant's motor experiences of daily living with 13 questions. (The numeric score for each question is between 0-4; 0=Normal,1=Slight,2=Mild,3=Moderate,4=Severe). Part II scores range from 0 to 52, with higher scores indicating more severe symptoms of PD.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=62 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=46 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
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	-1.06 score on a scale Standard Error 0.79	-2.65 score on a scale Standard Error 0.82

SECONDARY outcome

Timeframe: Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with an assessment for morning akinesia at Week 12.

Early morning "Off" status is assessed by the PD Diary as percentage of participants with early morning "Off" upon waking up at Week 12, based on the first morning symptom upon awakening on the last valid PD Diary day at Week 12. "Off" time is defined as periods of poor mobility, tremor, slowness, and stiffness and was assessed by the PD Diary.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=60 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=47 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
Early Morning "Off" Status (Morning Akinesia) at Week 12 of the Double-Blind Treatment Period	63.3 percentage of participants	17.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with a baseline and Week 12 assessment.

"On" time is defined as periods of good motor symptom control, and was assessed by the PD diary. The normalized "On" time without dyskinesia is defined as the hours of average daily normalized "On" time without dyskinesia as assessed by 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 dyskinesia collected over the 3 PD Diary days before randomization.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=62 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=47 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
Change From Baseline to Week 12 of the Double-Blind Treatment Period in Average Daily Normalized "On" Time Without Dyskinesia (Hours)	1.32 hours Standard Error 0.53	3.13 hours Standard Error 0.54

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with an assessment for PDSS-2.

The PDSS-2 addresses PD-specific sleep disturbances such as restless leg syndrome (RLS), morning akinesia, pain, and sleep apnea. The frequency is assessed for the 15 sleep problems based on a 5-point Likert-type scale (ranging from 0 \[never\] to 4 \[very often\]). Scores are calculated for each of the 3 domains (motor symptoms at night, PD symptoms at night, and disturbed sleep) as well as a total score. The PDSS-2 domain scores range from 0 to 20 and the total score is a sum of the 3 domains and ranges from 0 to 60. Higher scores indicate higher frequency and more severe impact of PD on sleep.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=59 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=44 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
Change From Baseline to Week 12 of the Double-Blind Treatment Period in Parkinson's Disease Sleep Scale-2 (PDSS-2) Total Score	-2.52 score on a scale Standard Error 1.12	-7.92 score on a scale Standard Error 1.18

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with an assessment for PDQ-39.

The PDQ-39 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. It evaluates the 8 dimensions of mobility, activities of daily living, emotional well-being, stigma, social support, cognition, and communication. Data from the PDQ-39 can be presented in either domain scores or as a summary index score. The full range of the PDQ-39 Summary Index score is from 0 (no patient-related symptoms/quality of life unaffected) to 100 (highest patient-related symptoms/low quality of life).

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=59 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=45 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
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	-2.28 score on a scale Standard Error 1.75	-6.38 score on a scale Standard Error 1.83

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with an assessment for EQ-5D-5L.

The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life. The EQ-5D-5L descriptive system comprises 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the subject's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. The health status is converted to an index value using the country-specific weighted scoring algorithm for the United States (US). The summary index value for the US ranges from a worst score of -0.109 to a best score of 1. An increase in the EQ-5D-5L total score indicates improvement.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=59 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=44 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
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	0.002 score on a scale Standard Error 0.021	0.051 score on a scale Standard Error 0.022

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with a baseline and Week 12 assessment for BK50 score.

The PKG wearable device is an innovative mobile health technology that provides continuous, objective, ambulatory assessment of the symptoms of PD including tremor, bradykinesia, dyskinesia, and daytime somnolence. For each participant, the PKG watch collected data continuously and an algorithm calculated a bradykinesia score every 2 minutes between 9am-6pm across multiple days. Among these scores for this participant at this visit, the median of all the score values is defined as BK50. A higher score indicates worse bradykinesia (there is no prespecified range of scores). The BK50 scores for all participants across all visits were then analyzed with mixed-effect model for repeated measures (MMRM) and the LS mean (model-based mean) was obtained from the model.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=59 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=66 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
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	-0.34 score on a scale Standard Error 0.52	1.38 score on a scale Standard Error 0.56

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with a baseline and Week 12 assessment for BK75-BK25.

The PKG wearable device is an innovative mobile health technology that provides continuous, objective, ambulatory assessment of the symptoms of PD including tremor, bradykinesia, dyskinesia, and daytime somnolence. For each participant, the PKG watch collected data continuously and an algorithm calculated a bradykinesia score every 2 minutes between 9am-6pm across multiple days. Among these scores for this participant at this visit, the median of all the score values is defined as BK50 (there is no prespecified range of scores). BK75-BK25 is the difference between the third quartile (BK75) and first quartile (BK25) bradykinesia scores, and this interquartile range is a measure of variability of bradykinesia. A higher score indicates a higher degree of variability in bradykinesia scores. The BK75 and BK 25 scores for all participants across all visits were then analyzed with mixed-effect model for repeated measures (MMRM) and the LS mean (model-based mean) was obtained from the model.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=59 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=66 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
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	0.13 score on a scale Standard Error 0.49	0.31 score on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with a baseline and Week 12 assessment for DK50.

The PKG wearable device is an innovative mobile health technology that provides continuous, objective, ambulatory assessment of the symptoms of PD including tremor, bradykinesia, dyskinesia, and daytime somnolence. For each participant, the PKG watch collected data continuously and an algorithm calculated a dyskinesia score every 2 minutes between 9am-6pm across multiple days. Among these scores for this participant at this visit, the median of all the score values is defined as DK50. A higher score indicates worse dyskinesia (there is no prespecified range of scores). The DK50 scores for all participants across all visits were then analyzed with mixed-effect model for repeated measures (MMRM) and the LS mean (model-based mean) was obtained from the model.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=59 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=66 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
Change From Baseline to Week 12 of the Double-Blind Treatment Period in Median Dyskinesia Score (DK50) as Assessed by the PKG Wearable Device	1.02 score on a scale Standard Error 1.38	-1.71 score on a scale Standard Error 1.41

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12 of the double-blind treatment period

Population: Full Analysis Set (FAS): all randomized participants who received any dose of study drug during the Double-Blind Treatment Period and who had baseline and at least 1 post-baseline observation for at least 1 efficacy assessment. Participants with a baseline and Week 12 assessment for DK75-DK25.

The PKG wearable device is an innovative mobile health technology that provides continuous, objective, ambulatory assessment of the symptoms of PD including tremor, bradykinesia, dyskinesia, and daytime somnolence. For each participant, the PKG watch collected data continuously and an algorithm calculated a dyskinesia score every 2 minutes between 9am-6pm across multiple days. Among these scores for this participant at this visit, the median of all the score values is defined as DK50 (there is no prespecified range of scores). DK75-DK25 is the difference between the third quartile (DK75) and first quartile (DK25) dyskinesia scores, and this interquartile range is a measure of variability of dyskinesia. A higher score indicates a higher degree of variability in dyskinesia scores. The DK75 and DK25 scores for all participants across all visits were then analyzed with mixed-effect model for repeated measures (MMRM) and the LS mean (model-based mean) was obtained from the model.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=59 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=66 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
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	2.72 score on a scale Standard Error 2.59	-2.77 score on a scale Standard Error 2.64

SECONDARY outcome

Timeframe: Day 2 up to Week 12 of the double-blind treatment period plus 30 days

Population: Safety Analysis Set: participants who received any dose of study drug during the Double-Blind Treatment Period.

The investigator or qualified designee evaluated the infusion site area (abdomen). A 2-part (numeric and letter grading) evaluation scale was used to assess irritation. Irritation - Numeric Grades: 0 = No evidence of irritation; 1 = Minimal erythema, barely perceptible; 2 = Moderate erythema, readily visible; or minimal edema, or minimal papular response; 3 = Erythema and papules; 4 = Definite edema; 5 = Erythema, edema, and papules; 6 = Vesicular eruption; 7 = Strong reaction spreading beyond the test site. Irritation - Letter Grades: A = No finding; B = Slight glazed appearance; C = Marked glazing; D = Glazing with peeling and cracking; E = Glazing with fissures; F = Film of dried serous exudates covering all or portion of the patch site; G = Small petechial erosions and/or scabs.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=67 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=74 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
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 At Least 1 Observation of Numeric Grade >= 5	0 Participants	10 Participants
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 At Least 1 Observation of Letter Grade >= D	0 Participants	6 Participants
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 At Least 1 Observation of Numeric Grade >= 5 or Letter Grade >= D	0 Participants	10 Participants
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 At Least 1 Observation of Numeric Grade >= 5 and Letter Grade >= D	0 Participants	6 Participants

SECONDARY outcome

Timeframe: From first dose of stabilization period treatment up to the first dose of the double-blind treatment period

Population: Oral LD/CD Analysis Set: all participants who received at least 1 dose of open label CD/LD IR tablets during the Oral CD/LD Stabilization Period.

An adverse event (AE) is defined as any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with treatment. An AE, whether associated with study drug or not, meeting any of the following criteria is considered a serious AE (SAE): results in death; is life-threatening; results in hospitalization or prolongation of hospitalization; is a congenital anomaly; results in persistent or significant disability/incapacity; is an important medical event requiring medical or surgical intervention to prevent a serious outcome. The severity of each AE is rated as mild, moderate, or severe, and having either a reasonable possibility or no reasonable possibility of relationship to study drug. Events were considered treatment emergent if they arose after the first dose of study drug.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=174 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Oral LD/CD Stabilization Period Any TEAE	41 Participants	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Oral LD/CD Stabilization Period Any Severe TEAE	3 Participants	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Oral LD/CD Stabilization Period Any TEAE Considered Related to Study Drug	2 Participants	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Oral LD/CD Stabilization Period Any TEAE Considered Associated With COVID-19 Infection	0 Participants	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Oral LD/CD Stabilization Period Any TEAE Leading to Premature Discontinuation of Study Drug	3 Participants	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Oral LD/CD Stabilization Period Any TEAE Leading Death	0 Participants	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Oral LD/CD Stabilization Period Any Serious TEAE	4 Participants	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Oral LD/CD Stabilization Period Deaths Related to COVID-19	0 Participants	—

SECONDARY outcome

Timeframe: From first dose of double-blind treatment up to Week 12 of the double-blind treatment period plus 30 days

Population: Safety Analysis Set: participants who received any dose of study drug during the Double-Blind Treatment Period.

An AE is defined as any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with treatment. An AE, whether associated with study drug or not, meeting any of the following criteria is considered an SAE: results in death; is life-threatening; results in hospitalization or prolongation of hospitalization; is a congenital anomaly; results in persistent or significant disability/incapacity; is an important medical event requiring medical or surgical intervention to prevent a serious outcome. The severity of each AE is rated as mild, moderate, or severe, and having either a reasonable possibility or no reasonable possibility of relationship to study drug. Adverse events of special interest include polyneuropathy, weight loss, somnolence, hallucinations/psychosis. Events were considered treatment emergent if they arose after the first dose of study drug.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=67 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=74 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
Number of Participants With TEAEs During the Double-Blind Treatment Period Any Adverse Event of Special Interest	25 Participants	59 Participants
Number of Participants With TEAEs During the Double-Blind Treatment Period Any TEAE	42 Participants	63 Participants
Number of Participants With TEAEs During the Double-Blind Treatment Period Any Serious TEAE	4 Participants	6 Participants
Number of Participants With TEAEs During the Double-Blind Treatment Period Any TEAE Leading to Death	1 Participants	0 Participants
Number of Participants With TEAEs During the Double-Blind Treatment Period Any TEAE Leading to Study Drug Discontinuation	1 Participants	16 Participants
Number of Participants With TEAEs During the Double-Blind Treatment Period Any Severe TEAE	1 Participants	7 Participants
Number of Participants With TEAEs During the Double-Blind Treatment Period Any TEAE Considered Related to Study Drug	15 Participants	52 Participants
Number of Participants With TEAEs During the Double-Blind Treatment Period Any Serious TEAE Considered Related With Infusion Pump	0 Participants	3 Participants
Number of Participants With TEAEs During the Double-Blind Treatment Period All Deaths (Includes Non-Treatment-Emergent Deaths)	1 Participants	0 Participants
Number of Participants With TEAEs During the Double-Blind Treatment Period Deaths Related to COVID-19	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Screening up to Week 12 of the double-blind treatment period

Population: Safety Analysis Set: participants who received any dose of study drug during the Double-Blind Treatment Period.

Measures analyzed for prespecified potentially clinically significant criteria: hematology (hematocrit, hemoglobin, red blood cells, white blood cells, neutrophils, bands, lymphocytes, monocytes, basophils, eosinophils, platelets, mean corpuscular hemoglobin, mean corpuscular volume concentration, prothrombin time, activated partial thromboplastin time), laboratory (blood urea nitrogen, creatinine, creatine phosphokinase, bilirubin, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase, sodium, potassium, calcium, phosphorus, uric acid, total protein, albumin, glucose, sodium bicarbonate, chloride, triglycerides, cholesterol, magnesium), special lab criteria (vitamin B12, vitamin B6, folate, homocysteine, methylmalonic acid), vital signs (diastolic and systolic blood pressure, pulse rate), ECG (heart rate, PR, and QTcF interval), urinalysis (specific gravity, ketones, pH, protein, glucose, blood, bilirubin).

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=67 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=74 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
Number of Participants With Potentially Clinically Significant Changes From Baseline in Hematology, Chemistry, Urinalysis, Special Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs) Hematology	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes From Baseline in Hematology, Chemistry, Urinalysis, Special Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs) Chemistry	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes From Baseline in Hematology, Chemistry, Urinalysis, Special Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs) Urinalysis	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes From Baseline in Hematology, Chemistry, Urinalysis, Special Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs) Special Laboratory Parameters	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes From Baseline in Hematology, Chemistry, Urinalysis, Special Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs) Vital Signs	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes From Baseline in Hematology, Chemistry, Urinalysis, Special Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs) ECGs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Screening up to Week 12 of the double-blind treatment period

Population: Safety Analysis Set: participants who received any dose of study drug during the Double-Blind Treatment Period. Participants with an assessment for C-SSRS.

The C-SSRS is a systematically administered instrument developed to track suicidal adverse events across a treatment study. The instrument is designed to assess suicidal behavior and ideation, track and assess all suicidal events, as well as the lethality of attempts. Suicidal ideation categories include the following: wish to be dead; nonspecific active suicidal thoughts; active suicidal ideation without intent to act; active suicidal ideation with some intent to act but no plan; active suicidal ideation with plan and intent. Suicidal behavior categories include the following: actual attempt; interrupted attempt; aborted attempt; preparatory acts or behavior; suicidal behavior; completed suicide.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=67 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=74 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
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 Participants With Any Suicidal Ideations	2 Participants	5 Participants
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 Participants With Any Suicidal Behaviors	0 Participants	0 Participants
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 Participants With Any Suicidal Behaviors or Ideations	2 Participants	5 Participants
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 Participants With Non-Suicidal Self-Injurious Behavior	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12 of the double-blind treatment period

Population: Safety Analysis Set: participants who received any dose of study drug during the Double-Blind Treatment Period. Participants with at least 1 post-baseline value for the specific QUIP-RS subscore.

The QUIP-RS measures the severity of symptoms and support a diagnosis of impulse control disorders and related disorders in PD. QUIP-RS subscores include gambling (score 0 to 16), sex (score 0 to 16), buying (score 0 to 16), eating (score 0 to 16), hobbyism-punding (score 0 to 32), and PD medication use (score 0 to 16). Higher scores represent a worse outcome.

Outcome measures

Outcome measures
Measure	LD/CD + Placebo for ABBV-951 n=65 Participants Participants received oral LD/CD and CSCI of placebo for ABBV-951 for 12 weeks.	ABBV-951 + Placebo for LD/CD n=67 Participants Participants received ABBV-951 by CSCI and oral placebo for LD/CD for 12 weeks.
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 Impulse Control Disorder: Buying Score	3 Participants	3 Participants
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 Impulse Control Disorder: Eating Score	5 Participants	6 Participants
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 Impulse Control Disorder: Gambling Score	2 Participants	0 Participants
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 Impulse Control Disorder: Sex Score	6 Participants	4 Participants
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 Additional Disorder: Hobbyism Punding Score	12 Participants	7 Participants
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 Additional Disorder: PD Medication Use Score	5 Participants	6 Participants

Adverse Events

LD/CD Stabilization Period

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

LD/CD + Placebo for ABBV-951

Serious events: 4 serious events

Other events: 18 other events

Deaths: 1 deaths

ABBV-951 + Placebo for LD/CD

Serious events: 6 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Global Medical Services

AbbVie

Phone: 1-800-633-9110

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place