A Study to Evaluate the Safety and Tolerability of ABBV-951 in Subjects With Parkinson's Disease (PD)

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

Treatment emergent adverse events of special interest are defined as any adverse event of infusion site infections, infusion site reactions, hallucinations/psychosis, falls and associated injuries, polyneuropathy (peripheral neuropathy), weight loss, or somnolence from the first dose of study drug until 30 days following last dose of study drug.

Skin tolerability was assessed using the Infusion Site Evaluation Scale, a 2-part numeric (0-7) and letter (A-G) grade scale, where a notable skin reaction is defined as a reaction with a numeric grade of 6 or 7 or a letter grade of D, E, F, or G. Any observation of infusion site reaction with irritation criteria > 2 or > C was recorded as an adverse event (AE).

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Samples for clinical laboratory tests were collected at study visits, and a certified central laboratory was used to process the samples and provide results.

Orthostatic blood pressure was measured after the participant had been supine (lying down with their face up) for at least 5 minutes and then, after the participant had been standing for 2 minutes. When vital sign measurements were scheduled at the same time as a blood collection, vital sign measurements were obtained prior to blood collection.

Orthostatic blood pressure was measured after the participant had been supine (lying down with their face up) for at least 5 minutes and then, after the participant had been standing for 2 minutes. When vital sign measurements were scheduled at the same time as a blood collection, vital sign measurements were obtained prior to blood collection.

Orthostatic pulse rate was measured after the participant had been supine (lying down with their face up) for at least 5 minutes and then, after the participant had been standing for 2 minutes. When vital sign measurements were scheduled at the same time as a blood collection, vital sign measurements were obtained prior to blood collection.

12-lead electrocardiograms (ECGs) were recorded at study visits after the participant had been supine for at least 5 minutes. Participants were instructed to remain stationary (no talking, laughing, deep breathing, sleeping, or swallowing) for approximately 10 seconds during the ECG recording. When an ECG was recorded at a time near that of a blood collection, the ECG was obtained prior to the blood collection. ECGs on Day 1 were recorded after initiation of the continuous subcutaneous infusion (CSCI) of ABBV-951 prior to the end of the study visit.

12-lead electrocardiograms (ECGs) were recorded at study visits after the participant had been supine for at least 5 minutes. Participants were instructed to remain stationary (no talking, laughing, deep breathing, sleeping, or swallowing) for approximately 10 seconds during the ECG recording. When an ECG was recorded at a time near that of a blood collection, the ECG was obtained prior to the blood collection. ECGs on Day 1 were recorded after initiation of the continuous subcutaneous infusion (CSCI) of ABBV-951 prior to the end of the study visit.

12-lead electrocardiograms (ECGs) were recorded at study visits after the participant had been supine for at least 5 minutes. Participants were instructed to remain stationary (no talking, laughing, deep breathing, sleeping, or swallowing) for approximately 10 seconds during the ECG recording. When an ECG was recorded at a time near that of a blood collection, the ECG was obtained prior to the blood collection. ECGs on Day 1 were recorded after initiation of the continuous subcutaneous infusion (CSCI) of ABBV-951 prior to the end of the study visit.

12-lead electrocardiograms (ECGs) were recorded at study visits after the participant had been supine for at least 5 minutes. Participants were instructed to remain stationary (no talking, laughing, deep breathing, sleeping, or swallowing) for approximately 10 seconds during the ECG recording. When an ECG was recorded at a time near that of a blood collection, the ECG was obtained prior to the blood collection. ECGs on Day 1 were recorded after initiation of the continuous subcutaneous infusion (CSCI) of ABBV-951 prior to the end of the study visit.

12-lead electrocardiograms (ECGs) were recorded at study visits after the participant had been supine for at least 5 minutes. Participants were instructed to remain stationary (no talking, laughing, deep breathing, sleeping, or swallowing) for approximately 10 seconds during the ECG recording. When an ECG was recorded at a time near that of a blood collection, the ECG was obtained prior to the blood collection. ECGs on Day 1 were recorded after initiation of the continuous subcutaneous infusion (CSCI) of ABBV-951 prior to the end of the study visit.

12-lead electrocardiograms (ECGs) were recorded at study visits after the participant had been supine for at least 5 minutes. Participants were instructed to remain stationary (no talking, laughing, deep breathing, sleeping, or swallowing) for approximately 10 seconds during the ECG recording. When an ECG was recorded at a time near that of a blood collection, the ECG was obtained prior to the blood collection. ECGs on Day 1 were recorded after initiation of the continuous subcutaneous infusion (CSCI) of ABBV-951 prior to the end of the study visit.

12-lead electrocardiograms (ECGs) were recorded at study visits after the participant had been supine for at least 5 minutes. Participants were instructed to remain stationary (no talking, laughing, deep breathing, sleeping, or swallowing) for approximately 10 seconds during the ECG recording. When an ECG was recorded at a time near that of a blood collection, the ECG was obtained prior to the blood collection. ECGs on Day 1 were recorded after initiation of the continuous subcutaneous infusion (CSCI) of ABBV-951 prior to the end of the study visit.

Upon awakening and every 30 minutes during their normal waking time, participants recorded their state in the Parkinson's Disease Diary (PD Diary) for 2 consecutive days prior to study visits.

"Off" time is defined as periods of poor mobility, tremor, slowness, and stiffness. The daily "On" and "Off" times were normalized to a typical waking day (16 hours) to account for different sleep patterns across participants. When "Off" was the first morning symptom upon awakening, this was considered morning akinesia in this study.

Baseline value is defined as the average of normalized "Off" time collected over the 2 PD Diary days before the Enrollment visit. Negative changes from Baseline indicate improvement.

Upon awakening and every 30 minutes during their normal waking time, participants recorded their state in the Parkinson's Disease Diary (PD Diary) for 2 consecutive days prior to study visits.

"On" time is defined as periods of good motor symptom control. The daily "On" and "Off" times were normalized to a typical waking day (16 hours) to account for different sleep patterns across participants.

Baseline value is defined as the average of normalized "On" time with troublesome dyskinesia collected over the 2 PD Diary days before the Enrollment visit. Negative changes from Baseline indicate improvement.

Upon awakening and every 30 minutes during their normal waking time, participants recorded their state in the Parkinson's Disease Diary (PD Diary) for 2 consecutive days prior to study visits.

"On" time is defined as periods of good motor symptom control. The daily "On" and "Off" times were normalized to a typical waking day (16 hours) to account for different sleep patterns across participants.

Baseline value is defined as the average of normalized "On" time without troublesome dyskinesia collected over the 2 PD Diary days before the Enrollment visit. Positive changes from Baseline indicate improvement.

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is an investigator-used rating tool to follow the longitudinal course of Parkinson's Disease (PD). Part I assesses the participant's non-motor aspects of experiences of daily living (nM-EDL) with 13 questions. (The numeric score for each question is between 0-4; 0=Normal,1=Slight,2=Mild,3=Moderate,4=Severe). Part I scores range from 0 to 52, with higher scores indicating more severe symptoms of PD. Negative changes from Baseline indicate improvement.

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is an investigator-used rating tool to follow the longitudinal course of Parkinson's Disease (PD). Part II assesses the participant's motor experiences of daily living (M-EDL) 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. Negative changes from Baseline indicate improvement.

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is an investigator-used rating tool to follow the longitudinal course of Parkinson's Disease (PD). Part III assesses the participant's motor examination (including Hoehn and Yahr stage) with 33 questions. (The numeric score for each question is between 0-4; 0=Normal,1=Slight,2=Mild,3=Moderate,4=Severe). Part III scores range from 0 to 132, with higher scores indicating more severe symptoms of PD. Negative changes from Baseline indicate improvement.

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is an investigator-used rating tool to follow the longitudinal course of Parkinson's Disease (PD). Part IV assesses the participant's motor complications with 6 questions. (The numeric score for each question is between 0-4; 0=Normal,1=Slight,2=Mild,3=Moderate,4=Severe). Part IV scores range from 0 to 24, with higher scores indicating more severe symptoms of PD. Negative changes from Baseline indicate improvement.

The PDSS-2 consists of 15 questions that evaluate motor and non-motor symptoms at night and upon wakening, as well as disturbed sleep grouped into 3 domains: motor symptoms at night (5 items), Parkinson's Disease (PD) symptoms at night (5 items), and disturbed sleep (5 items). 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] with the exception of Question 1 score ranging from 0 [very often] to 4 [never]). Scores are calculated for each of the 3 domains 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. Negative changes indicate improvement from Baseline.

The Parkinson's Disease Questionnaire (PDQ-39) is a disease-specific instrument designed to measure aspects of health that are relevant to participants with Parkinson's Disease (PD), and which may not be included in general health status questionnaires. 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 more severe symptoms of the disease such as tremors and stiffness. The results 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). Negative changes indicate improvement from Baseline.

The EuroQol 5-dimension questionnaire (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 participant'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.