Clinical trial NCT04380142
Conditions: Parkinson's Disease (PD)
Keywords: Parkinson's Disease (PD) ABBV-951 Levodopa/Carbidopa (LD/CD) Levodopa Phosphate/Carbidopa Phosphate (LDP/CDP)
Sponsor: AbbVie
Start date: 2020-10-19; Completion date: 2021-09-29
Enrollment: 174 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Detailed description:

Arms: arm 1: 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 arm 2: 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
Interventions: intervention 1: ABBV-951 intervention 2: Placebo for Levodopa/Carbidopa (LD/CD) intervention 3: Levodopa/Carbidopa (LD/CD) intervention 4: Placebo for ABBV-951
Intervention descriptions: intervention 1: Solution for continuous subcutaneous infusion (CSCI) intervention 2: Oral capsule intervention 3: Oral encapsulated tablet intervention 4: Solution for continuous subcutaneous infusion (CSCI)

Protocol documents:
Prot_000.pdf: 


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
8
2.1
BACKGROUND AND RATIONALE
8
2.2
BENEFITS AND RISKS TO SUBJECTS
9
3
OBJECTIVES AND ENDPOINTS
9
3.1
PRIMARY ENDPOINT
10
3.2
SECONDARY ENDPOINTS
10
3.3
SAFETY ENDPOINTS
10
4
INVESTIGATIONAL PLAN
11
4.1
OVERALL STUDY DESIGN AND PLAN
11
4.2
DISCUSSION OF STUDY DESIGN
18
5
STUDY ACTIVITIES
22
5.1
ELIGIBILITY CRITERIA
22
5.2
CONTRACEPTION RECOMMENDATIONS
25
5.3
PROHIBITED MEDICATIONS AND THERAPY
26
5.4
PRIOR AND CONCOMITANT THERAPY
27
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
28
5.6
TEMPORARY SUSPENSION OF STUDY DRUG TREATMENT
29
5.7
FOLLOW-UP AFTER SUBJECT DISCONTINUATION OF STUDY DRUG OR STUDY
29
5.8
STUDY DRUG AND STUDY DEVICES
30
5.9
RANDOMIZATION/DRUG ASSIGNMENT
39
5.10
PROTOCOL DEVIATIONS
40
6
SAFETY CONSIDERATIONS
40
6.1
COMPLAINTS AND ADVERSE EVENTS
40
7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
46
7.1
STATISTICAL AND ANALYTICAL PLANS
46
7.2
DEFINITION FOR ANALYSIS POPULATIONS
47
Page 2 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
7.3
STATISTICAL ANALYSES FOR EFFICACY
47
7.4
STATISTICAL ANALYSES FOR SAFETY
49
7.5
INTERIM ANALYSIS
51
7.6
MULTIPLICITY ADJUSTMENT AND OVERALL TYPE I ERROR CONTROL
51
7.7
SAMPLE SIZE DETERMINATION
51
8
ETHICS
52
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD (IEC/IRB)
52
8.2
ETHICAL CONDUCT OF THE STUDY
52
8.3
SUBJECT CONFIDENTIALITY
52
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
52
10
DATA QUALITY ASSURANCE
53
11
COMPLETION OF THE STUDY
53
12
REFERENCES
53
LIST OF TABLES
TABLE 1.
INFUSION LOADING DOSE DETERMINATION
19
TABLE 2.
STARTING INFUSION RATES DETERMINATION AND LIMITS ON CONTINUOUS INFUSION RATE 
DURING STUDY
20
TABLE 3.
PROHIBITED MEDICATIONS
27
TABLE 4.
ALLOWED CONCOMITANT MEDICATIONS/THERAPY
28
TABLE 5.
ALLOWED RESCUE MEDICATIONS/THERAPY
28
TABLE 6.
IDENTITY OF STUDY DRUG
30
TABLE 7.
IDENTITY OF STUDY DEVICES
31
TABLE 8.
GUIDANCE FOR CONVERSION FROM LD-CONTAINING MEDICATIONS TO CD/LD IR
33
Page 3 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
LIST OF FIGURES
FIGURE 1.
STUDY DESIGN SCHEMATIC
12
LIST OF APPENDICES
APPENDIX A.
STUDY SPECIFIC ABBREVIATIONS AND TERMS
54
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
57
APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
58
APPENDIX D.
ACTIVITY SCHEDULE
59
APPENDIX E.
PROTOCOL SUMMARY OF CHANGES
68
APPENDIX F.
OPERATIONS MANUAL
69
Page 4 of 115








STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
2 INTRODUCTION
2.1 Background and Rationale
Why This Study is Being Conducted
ABBV-951 (carbidopa phosphate/levodopa phosphate [CDP/LDP]) is soluble formulation of 
carbidopa/levodopa (CD/LD) prodrugs that is deliverable by continuous subcutaneous infusion (CSCI).
Patients with Parkinson's disease (PD) require a therapeutic approach that is tailored to their unique 
needs and responses to LD.  ABBV-951 enables continuous, subcutaneous, and individualized delivery of 
CD/LD, covering the wide range of LD doses required to adequately control motor symptoms in patients
with advanced PD (aPD).  Therefore, this treatment may provide an alternative therapy to many patients 
whose motor fluctuations are inadequately controlled by their current treatment.
Systemic and local tolerability have been measured in animal models, and in the clinical setting with 
generally favorable outcomes.  Local irritation was assessed in dogs at a CDP/LDP 50/200 mg/mL 
concentration, following CSCI for 28 days with a fixed indwelling catheter at a rate of 0.1 or 
0.25 mL/hour (120/480 mg/day or 300/1200 mg/day, respectively).  120/480 mg/day was well tolerated, 
and the infusion site findings were similar to those of the vehicle control without signs of irritation or 
inflammation stemming from ABBV-951.  Findings at the infusion site of animals treated with the higher 
infusion rate (0.25 mL/hour) were confounded by a concurrent bacterial infection, and it was not 
possible to clearly determine whether ABBV-951 was well tolerated; however, the infusion of ABBV-951 
at the same concentration (50/200 mg/mL), but at a higher infusion rate (0.5 mL/hour) for fewer days 
(5 days) was well tolerated, with only minimal signs of irritation at the infusion site.  In cohorts from the 
Phase 1 study in healthy volunteers (Study M15-733), in which ABBV-951 was administered as a loading 
dose followed by a continuous infusion for up to 72 hours, levodopa exposure showed a low degree of 
fluctuation.  ABBV-951 was generally well tolerated, with only mild reports of pain at the infusion site 
related to high flow rates used to deliver loading doses.  These reports of infusion site pain were 
significantly reduced when the flow rate was adjusted to deliver the loading dose over a longer period of 
time.  No other local tolerability issues were observed, and no subject discontinued the study due to 
these events.  Skin adverse events (AEs) have been reported in other Phase 1 studies in subjects with PD
where ABBV-951 was administered at therapeutic doses for 24 or 72 hours (Study M15-738) or for up to 
28 days (Study M15-739).  Most events have been mild in severity and manageable.  No clinically 
concerning differences in skin tolerability were detected after 10 consecutive days of 48/960 mg 
CDP/LDP and an equivalent volume of saline infused over 24 hours/day in opposite sides of the 
abdomen in healthy volunteers (Study M18-763).
The dose ranges of ABBV-951 to be used in this study are similar to those administered in the Phase 1 
studies in subjects with PD (Studies M15-738 and M15-739) and in the ongoing long-term safety study in 
aPD (Study M15-741).
This randomized, double-blind, double-dummy, parallel-group, active-controlled, multicenter, Phase 3 
study will be conducted in an outpatient setting to evaluate efficacy, safety, and tolerability of a 
24-hour/day CSCI of ABBV-951 versus oral CD/LD for 12 weeks in subjects with aPD.
Page 8 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
2.2 Benefits and Risks to Subjects
The combination of oral LD and DOPA decarboxylase inhibitors, such as CD or benserazide, has been 
used for many years in patients with PD to control motor symptoms, and the systemic safety profile of 
CD/LD is well established.  Achieving stable plasma LD concentrations through continuous infusion has 
been demonstrated previously with LCIG and resulted in greater efficacy than oral CD/LD as assessed by 
a reduction in average daily "Off" time accompanied by increased "On" time without troublesome 
dyskinesia.  Phase 1 studies showed that plasma LD concentrations from CSCI of ABBV-951 can be 
maintained stable and within the patient's therapeutic window.
Potential risks of receiving an ABBV-951 dose lower than the therapeutic dose required to control PD 
symptoms include experiencing an exacerbation of PD symptoms ("Off" state) characterized by 
increased difficulty with movement, tremor, and stiffness.  Potential risks of receiving an ABBV-951 dose 
higher than the therapeutic dose include experiencing dyskinesias (abnormal or uncontrolled 
movements) and hallucinations.  Other anticipated risks are well characterized LD-related side effects, 
including nausea, vomiting, and dizziness; however, not all of the potential side effects of ABBV-951 are 
known.
Subjects may also experience general discomfort or inconvenience related to study procedures. Since 
ABBV-951 is administered as a CSCI, there is a potential for issues related to infusion site tolerability.  
This may include infusion site irritation and inflammation (swelling, redness, pain, itching), bruising, skin 
infection, and discomfort related to the feeling of liquid flowing through the needle/cannula.  Data from 
preclinical and clinical studies (both in subjects with PD [Studies M15-738 and M15-739] and in healthy 
volunteers [Study M18-763]) show that infusion is generally well tolerated; however, the infusion rates 
(i.e., flow rates) in the current study are anticipated to be higher than those used in the study with 
healthy volunteers and to be delivered for a longer period of time compared with the studies in subjects 
with PD; therefore, assessment of local tolerability at the infusion site is a focus of this study.
For details, please see the safety data in the ABBV-951 investigator's brochure.1
ABBV-951 metabolizes into LD and CD, sharing the same characteristics of these compounds, which are 
commonly used as symptomatic treatment of PD globally. Based on the limited information available to 
date, exposure to ABBV-951 does not appear to pose additional risks to study participants because of 
the coronavirus disease-2019 (COVID-19).
3 OBJECTIVES AND ENDPOINTS
Primary

To demonstrate the superiority of CSCI of ABBV-951 over oral CD/LD immediate release (IR) 
tablets for the treatment of motor fluctuations in subjects with aPD after 12 weeks of therapy.
Clinical Hypothesis:  The 24-hour/day CSCI of ABBV-951 will increase "On" time without troublesome 
dyskinesia, reduce "Off" time, and improve the Motor Aspects of Experiences of Daily Living (M-EDL) 
compared to CD/LD IR tablets in patients with aPD whose motor fluctuations are inadequately
controlled by their current PD medications.
Page 9 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Secondary

To assess the local and systemic safety and tolerability of ABBV-951 delivered as a CSCI for 
24 hours daily for 12 weeks.
3.1 Primary Endpoint
The primary endpoint is the change from Baseline to Week 12 of the Double-Blind Treatment in "On" 
time without troublesome dyskinesia (hours) ("On" time without dyskinesia plus "On" time with 
non-troublesome dyskinesia), based on the PD Diary (normalized to a 16-hour waking day and averaged 
over 3 consecutive days).  The baseline value is defined as the average of normalized "On" time without 
troublesome dyskinesia collected over the 3 PD Diary days before randomization (V6).
3.2 Secondary Endpoints
Key Secondary Endpoints

Change from Baseline to Week 12 of the Double-Blind Treatment in:

Hours of average daily normalized "Off" time as assessed by the PD Diary.

M-EDL as assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating 
Scale (MDS-UPDRS) Part II score.

Presence of morning akinesia at Week 12 (defined as reporting "Off" status as the first morning 
symptom upon awakening) as assessed by the PD Diary.
Other Secondary Endpoints

Change from Baseline to Week 12 in hours of average daily normalized “On” time without 
dyskinesia as assessed by the PD Diary.

Change from Baseline to Final Visit in sleep symptoms as assessed by the Parkinson's Disease 
Sleep Scale-2 (PDSS-2) total score.

Change from Baseline to Final Visit in PD-related quality of life as assessed by the Parkinson's 
Disease Questionnaire-39 item (PDQ-39) summary index.

Change from Baseline to Final Visit in health-related quality of life as assessed by the EQ-5D-5L
summary index.

Change from Baseline to Week 12 in PD symptoms as assessed by the Parkinson's 
KinetiGraph®/Personal KinetiGraph® (PKG) wearable device (based on local country regulations).
3.3 Safety Endpoints
Safety endpoints are local tolerability (as measured by the Infusion Site Evaluation scale), AEs, serious 
AEs (SAEs), AEs of special interest (AESIs), clinical laboratory values, vital signs, electrocardiograms
(ECGs), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the Questionnaire for 
Impulsive-Compulsive Disorders in Parkinson's Disease – Rating Scale (QUIP-RS).
Page 10 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
This is a Phase 3, randomized, double-blind, double-dummy, 12-week, parallel group, active-controlled, 
multicenter study assessing the efficacy, safety, and tolerability of 24-hour/day CSCI of ABBV-951 in the 
treatment of subjects with aPD whose motor fluctuations are inadequately controlled by their current 
medications.  Approximately 130 adult subjects will be randomized in a 1:1 ratio to receive 24-hour/day 
CSCI of ABBV-951 plus oral placebo capsules or 24-hour/day CSCI of placebo solution plus oral 
encapsulated CD/LD IR tablets for 12 weeks. See Section 5.1 for eligibility criteria.  Approximately
80 sites will participate.
Adverse events, clinical laboratory test results, ECGs, vital signs, and C-SSRS will be monitored 
throughout the study (see Section 3.6, Section 3.15, Section 3.14, Section 3.11, and Section 3.9, 
respectively, of the Operations Manual [Appendix F]).
The study consists of a Screening Period, an Oral CD/LD Stabilization Period, and a Double-Blind 
Treatment Period (randomization, CSCI Optimization Phase, Maintenance Phase).  On the day of 
randomization, subjects will be required to arrive at the clinic in a practically defined "Off" state, 
i.e., after a 12-hour withdrawal of all PD medications.  A schematic of the study is shown in Figure 1 (all 
timing is in calendar days).  Details regarding study procedures are located in Section 3 of the Operations 
Manual (Appendix F).
The study includes 13 site visits.  In rare situations where a visit cannot be completed onsite due to an 
extenuating event (e.g., genuine emergency, natural disaster, COVID-19-related disruptions), some 
assessments may be performed remotely or via a home health service.  Refer to the Operations Manual 
(Appendix F) for further guidance.
Page 11 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Figure 1.
Study Design Schematic
CD/LD = carbidopa/levodopa; CSCI = continuous subcutaneous infusion; D = Day; IR = immediate release; 
PD = Parkinson's disease; V = Visit
a.
V3 should occur at least 6 days after V1 to allow test results from V1 results to be fully available for review and to provide 
adequate training and confirm the patient’s familiarity with the infusion delivery system.
b.
Screening Period activities will last at least 6 days; PD Diaries will be collected for at least 3 consecutive days during the 
Screening Period prior to V2; collection of PD Diaries may be repeated only once for 3 additional consecutive days leading 
up to V3 prior to the start of the Oral CD/LD Stabilization Period.
c.
The activities of the Oral CD/LD Stabilization Period are expected to take 14 to 21 days to accommodate scheduling, 
additional unscheduled visits, and, when allowed, repeated assessments.  PD Diaries will be collected for at least 
3 consecutive days before Day –1).
d.
If a subject prematurely discontinues study participation or completes the study and does not enter the open-label
extension Study M20-098, a follow-up visit or follow-up phone call will be completed 30 days after the last day of study
drug, if the subject is willing, to ensure all treatment-emergent AEs/SAEs have resolved.
Note:
As allowed by local regulations, subjects will be required to wear the PKG watch (wearable device) (refer to the 
currently approved manufacturer's directions) from the beginning of V1 to Day 85 Visit (V13).  "As allowed by local 
regulations" is applicable to all wearable device references throughout this protocol and its appendices.  The 
AbbVie Therapeutic Area Medical Director (TA MD) should be consulted if, in the opinion of the Investigator, there 
are circumstances that might interfere with the use of the PKG device (e.g., religious reasons, atopic dermatitis).
Page 12 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Screening Period (Duration:  6 to 60 Days)
The Screening Period includes 2 visits: Visit 1 (V1) and Visit 2 (V2). V3 should occur at least 6 days after 
V1 to allow test results from V1 to be fully available for review and to provide adequate training and 
confirm the patient's familiarity with the infusion delivery system.  Screening Period activities are 
expected to take 6 to 60 days to accommodate scheduling and, when allowed, repeat assessments. The 
visits during this period are as follows:

V1: Eligibility will be confirmed, including review of vitamin B12 requirements. Subjects with a 
low vitamin B12 or low-normal vitamin B12 and high MMA plasma level may undergo 
supplemental vitamin therapy.  Retest for vitamin B12 is allowed during the Screening Period 
without repeating other screening procedures. Starting at V1, subjects (and caregivers, if 
applicable) will be trained on the correct use of the Phillips-Medisize Parkinson's Disease 
Subcutaneous (PM-PDSC) Pump Delivery System.  V1 may be split into different visits.

V2: Leading up to V2, subjects (and caregivers, if applicable), will continue to be trained on the 
correct use of the PM-PDSC Pump Delivery System at the study site or the subject's home.  At
V2, the subject (or caregiver) must demonstrate the understanding and correct use of the 
delivery system, including the insertion of the cannula into the subject's abdomen, which will be 
assessed by the investigator or designee using the PM-PDSC Knowledge and Skills Checklist. At 
the investigator or designee's discretion, the demonstration of understanding and correct use of 
the delivery system may be repeated at an unscheduled visit prior to the start of the Oral CD/LD 
Stabilization Period (V3). The Screening Period must not be extended beyond 60 days to 
accommodate this.  Subjects who fail this requirement must be screen failed.
To increase familiarity with the PM-PDSC Pump Delivery System, subjects will have the opportunity to 
wear a mock infusion delivery system, where available, during the daily activities of the Screening 
Period. Subjects will also become familiar with the PKG wearable device and the PD Diary. Prior to the 
Oral CD/LD Stabilization Period, subjects must experience an average daily "Off" time of at least 
2.5 hours over 3 consecutive PD Diary days and a minimum of 2 hours each day to remain eligible for the 
study.  The PD Diaries used for this evaluation must have at least 44 of the 48 daily entries completed.  
Subjects who fail to meet this requirement prior to V2 may repeat the PD Diary for 3 additional 
consecutive days during the Screening Period. If the "Off" time criterion is still not met, subjects must 
be screen failed.
Note: At V2 and prior to a subject's enrollment (V3), the investigator or designee must confirm eligibility 
criteria in EDC. The TA MD or designee (contact information on cover page) are readily available to 
discuss any questions the Investigator or designee may have regarding appropriateness of a specific 
subject or the criteria. The decision to enroll the subject is ultimately the investigator's responsibility.
In rare situations (e.g., genuine emergency, natural disaster, or for COVID-19-related disruptions), where 
screening cannot be completed within 60 days, the TA MD must be contacted for a case-by-case review 
and approval of potential rescreens.
Rescreened subjects will need to repeat all screening visits and screening procedures (except for the 
concordance test) and demonstrate that they still meet eligibility criteria and suitability to participate in 
the study prior to enrollment (V3).
Page 13 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Oral CD/LD Stabilization Period (Duration:  14 to 21 Days)
The Oral CD/LD Stabilization Period includes 3 visits: Visit 3 (V3), Visit 4 (V4), and Visit 5 (V5).  V4 is 
optional at the investigator's discretion.  All visits during the Oral CD/LD Stabilization Period will have a 
window of ± 2 days and subjects should be on the prescribed oral CD/LD IR regimen and concomitant PD 
medication as much as possible during the Oral CD/LD Stabilization Period until 12 hours prior to Visit 6 
(V6) even if a visit is not occurring on the designated study day.  The activities of the Oral CD/LD 
Stabilization Period are expected to take 14 to 21 days to accommodate scheduling and, when allowed, 
repeat assessments.  The visits during this period are as follows:

V3:  All LD-containing medications (regardless of formulation), as well as those containing 
catechol-O-methyltransferase (COMT) inhibitors, will be converted to an equivalent amount of 
CD/LD IR.  All COMT inhibitors will be suspended. All other concomitant PD medications 
(e.g., dopamine-agonists, monoamine oxidase B [MAO-B] inhibitors, safinamide, amantadine, 
istradefylline), although allowed, must remain unchanged until study completion, unless specific 
safety conditions dictate their modification.  The new therapeutic regimen will consist of only 
CD/LD IR plus allowed non-LD-containing PD medications, if needed, and it should aim to 
achieve the best control of subjects' PD symptoms.  After a brief clinical examination, subjects 
will be given their newly established therapeutic regimen of CD/LD IR tablets that subjects will 
initiate the morning of the following day.  The CD/LD 25/100 mg IR tablets must be used whole; 
no split, crushed, or partial tablets may be used.  Enrollment in the Oral CD/LD Stabilization 
Period and dispensing open-label CD/LD IR should be the last procedure of V3.

Optional V4:  Seven days after V3, the investigator will assess the subjects' PD symptoms and 
may adjust their CD/LD IR regimen, if needed.  Concomitant PD medications must remain 
unchanged.  If no adjustments to the CD/LD IR therapeutic regimen are needed for a full week 
after V3, subjects may skip the V4 assessments and proceed directly to the V5 assessments.  If
before or at V4, more adjustments are needed, then subjects will complete V4 assessments and 
return a week later for V5.

V5 (Baseline Visit):  Subjects will return to the clinic a week before randomization and complete 
V5 study activities.  No further adjustments to the oral CD/LD IR may be made during V5.  
Subjects will be asked to keep their oral CD/LD IR therapeutic regimen unchanged until Visit 6
(V6, Day 1, Randomization Visit).  Subjects (and caregivers, if applicable) will continue to be 
trained on the correct use of the PM-PDSC Pump Delivery System leading up to V5 and must 
again demonstrate at V5 the understanding and correct use of the delivery system, including the 
insertion of the cannula into the subject's abdomen, as assessed by the investigator or designee
using the PM-PDSC Knowledge and Skills Checklist. Subjects who fail this requirement must be 
prematurely discontinued.  V5 will be the Baseline Visit, unless otherwise indicated.
During the Oral CD/LD Stabilization Period, the CD/LD IR therapeutic regimen may be adjusted over the 
phone or in the office, both will be recorded as unscheduled visits if changes to the CD/LD IR therapeutic 
regimen occur between scheduled visits; however, no changes to the oral CD/LD IR therapeutic regimen 
should be made for at least 7 days before Day 1 (Randomization Visit, V6), unless for medical necessity 
(safety).  Concomitant PD medications must remain unchanged.
Open-label CD/LD 25 mg/100 mg (25/100) IR tablets will be dispensed to subjects for use during the Oral 
CD/LD Stabilization Period.
Page 14 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Double-Blind Treatment Period (Duration:  85 Days)
The Double-Blind Treatment Period includes 8 study visits and has a duration of 12 weeks.  All 
Double-Blind Treatment Period visits will have a window of ± 3 days with the exception of V6, which has 
a window of + 2 days, and V7, which has no window.  Subjects should remain on the double-blind study 
drug as much as possible through D85/Premature Discontinuation Visit (V13) even if a visit is not 
occurring on the designated study day.
Randomization (Day 1 [V6]):
Subjects will arrive in the morning for their Randomization Visit in a practically defined "Off" state.  No 
medications to treat PD symptoms should be taken for at least 12 hours before V6 to provide a clear 
picture of the untreated symptomatology of the disease.
After a clinical examination, continued study eligibility will be validated, which includes confirming the 
presence of at least 2 hours of "Off" time each day for 3 consecutive days on the PD Diary (PD Diaries 
must be completed prior to Day –1). The PD Diaries used for this evaluation must have at least 44 of the 
48 daily entries completed.  Subjects who do not meet this requirement must be prematurely 
discontinued from the study.
Subjects who meet all the eligibility criteria and continue to be suitable to participate in the study, per 
investigator's or designee's adjudication, will be randomized 1:1 into one of the 2 treatment arms:

24-hour/day CSCI of ABBV-951 plus oral placebo capsules for CD/LD IR
OR

24-hour/day CSCI of placebo solution for ABBV-951 plus oral encapsulated CD/LD IR tablets
CSCI Optimization Phase (Day 1 [V6] through Day 29 [V11]):
Immediately following randomization on Day 1 (V6), subjects will begin the Double-Blind Treatment 
Period.  In a blinded fashion, subjects will receive a dual loading dose on Day 1 with both oral study drug 
and study drug solution (see Table 1).

For the oral loading dose, the number of study drug capsules will be identical to the number of 
CD/LD IR tablets taken as the first dose of the day at the end of the Oral CD/LD Stabilization 
Period.

For the loading dose solution, the volume of study drug solution will be calculated based on the 
volume of ABBV-951 delivering an amount of LD equivalent to the number of CD/LD IR tablets 
taken as the first dose of the day at the end of the Oral CD/LD Stabilization Period.  The loading 
dose solution will be delivered subcutaneously via the pump.
After the loading dose, subjects will start their infusion of blinded study drug solution and will 
concurrently receive blinded oral study drug.
Page 15 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Note: a loading dose is needed only on Day 1. This feature is then disabled on the PM-PDSC Pump for 
the duration of the study by setting the loading dose volume to 0.00 mL.  The study design requires that 
every subject be switched to open-label LD/CD if the infusion has been interrupted for more than 1 hour
in order to maintain subjects in the "On" state before restarting the continuous infusion and prevent 
unblinding.
During the CSCI Optimization Phase, only changes to the CSCI will be permitted; oral study drug and 
allowed concomitant PD medications must be maintained at the already optimal and stabilized pre-
randomization dose and schedule.  Changes to the concomitant PD medications are not allowed, unless 
necessary for safety reasons.
During the CSCI Optimization Phase, subjects will be evaluated on Day 2 (V7), Day 8 (V8), Day 15 (V9), 
Day 22 (V10) (optional), Day 29 (V11), and any intervening days as needed (recorded as unscheduled 
visits).  During each visit, the investigator will assess the subject's PD symptoms and may adjust the 
subject's CSCI infusion rate based on the subject's clinical response.  Optimal clinical response is defined 
by maximizing the functional "On" time and minimizing the number of "Off" episodes during the day.  
This optimization also minimizes "On" time with troublesome dyskinesia.
Subjects will be instructed to record, in the Subject Dosing Diary, all oral CD/LD IR tablets taken as 
rescue medication during the Double-Blind Treatment Period (i.e., not only 3 consecutive days prior to 
study visits). Subjects will also track infusion sites in the Infusion Site Rotation Tool to help guide their 
rotation pattern and prevent overuse of an infusion site area throughout the Double-Blind Treatment 
Period.
During the CSCI Optimization Phase, study visits will occur as follows:

Day 1 (V6) Randomization

Day 2 (V7)

Day 8 (V8)

Day 15 (V9)

Optional Day 22 (V10) – If the investigator determines no adjustments to the infusion rate are 
needed through phone contact, subjects may skip V10.

Day 29 (V11)
Maintenance Phase (After Day 29 [V11] through Day 85 [V13]):
After Day 29 (V11), subjects will begin the Maintenance Phase and should maintain stable treatment
regimens of blinded study drug solution and blinded oral study drug as well as other concomitant 
medications, including any PD medications that are still being administered.  Dose adjustments of 
non-study-drug medications may be made only if considered medically necessary (e.g., management of 
dyskinesia), in the investigator's opinion.  In case of sudden deterioration of clinical condition, rescue 
tablets of CD/LD IR may be taken.
Subjects will be instructed to record, in the Subject Dosing Diary, all oral CD/LD IR tablets taken as 
rescue medication during the Double-Blind Treatment Period (i.e., not only 3 consecutive days prior to 
Page 16 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
study visits).  Any changes to medications, including the optimized randomized regimens, should be 
recorded in the electronic case report form (eCRF).
During the Maintenance Phase, study visits will occur as follows:

Day 57 (V12)

Day 85 (V13) or premature discontinuation
Dermatologic Assessments
Subcutaneous delivery of study drug calls for attention during the procedures related to administration 
(general hygiene, skin disinfection, maintenance of a dirt-free environment while manipulating the 
system components, etc.) and subject and/or caregiver training and adherence to proper techniques is 
critical.  Manipulation at the level of the cannula pad due to disconnection and reconnection of the 
tubing might also lead to skin irritation, abrasion, and other lesions which could evolve to infection and 
cellulitis because of bacterial contamination.  Infusion site reactions including erythema, pain, or any 
other inflammation signs, have been observed.1  Most are mild or moderate in severity and generally 
self-resolving, with or without therapy.  Some cases might require further management and clinical 
correlation is recommended.  Investigators should obtain dermatologic consult if needed.
Absorption of study drug by the subcutaneous tissue may vary depending on the volume of drug 
solution infused/day, skin characteristics, hydration, etc.  Accumulation of study drug under the skin, 
manifesting as an elevated area of the skin, with or without induration and/or seepage of study drug 
from the infusion site after removal of the cannula or during infusion, might be a sign of reduced 
absorption, which could lead to irritation of the area and increased risk of bacterial contamination.  In 
these cases, more frequent rotation of the infusion site (using a new cannula/infusion set) is 
recommended in order to minimize the risk of infections.
If any moderate to severe infusion site-related AE, such as cellulitis/abscess formation, ecchymoses, 
subcutaneous nodules, or scarring occurs, or if any infusion site-related reaction is assessed with an 
irritation numeric grade equal to 7 on the Infusion Site Evaluation scale (see Section 3.7 of the 
Operations Manual in Appendix F), the investigator, or designee, is instructed to do the following:
1.
Photograph the skin reaction and follow the appropriate procedure for submission of the 
photographs.  In rare situations where an assessment or visit cannot be completed onsite due to 
an extenuating event (e.g., genuine emergency, natural disaster, COVID-19-related conditions), 
the subject may be asked to obtain and submit a self-captured photograph of the skin reaction.
2.
Refer the subject to a dermatologist for comprehensive evaluation (including skin biopsy, if 
applicable), treatment, and follow-up per standard practice.  The subject should be referred to a 
dermatologist within 2 business days after the photographs are taken.  The dermatologic visit 
should be completed within 2 weeks after identification of the AE or skin reaction that meets 
the above criteria.  While an in-person dermatology evaluation is preferred, this assessment 
may be performed as a telemedicine visit per the dermatologist's standard practice.
Page 17 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Study Drug Regimens during the Double-Blind Treatment Period
Subjects will receive both a 24-hour/day CSCI of the blinded study drug solution and blinded oral study 
drug.  The starting continuous infusion rate will be calculated based on the total amount of LD that the 
subject receives during the waking time at the end of the Oral CD/LD Stabilization Period and a 
conversion algorithm based on the pharmacokinetic characteristics of ABBV-951.  Subjects will receive 
the blinded oral study drug that will match, in number of tablets and dosing frequency, the therapeutic 
schedule that was achieved during the Oral CD/LD Stabilization Period.
The investigator may adjust the prescribed infusion rate only during the CSCI Optimization Phase.  Oral 
study drug must remain unchanged for the entire Double-Blind Treatment Period.
Rescue Medication
All subjects will receive open-label CD/LD IR tablets for use as rescue medication.  Once the 
Double-Blind Treatment Period has been initiated, rescue tablets should only be used in the case of a 
serious medical need, such as rapid deterioration of motor symptoms.  Rescue doses during the 
Double-Blind Treatment Period are the only doses taken during the study that allow the administration 
of half tablets of CD/LD IR.  Subjects will be instructed to record, in the Subject Dosing Diary, all oral 
CD/LD IR tablets taken as rescue medication during the Double-Blind Treatment Period (i.e., not only 
3 consecutive days prior to study visits).
Post-Treatment Activities
Subjects who complete the study may be eligible for the open-label extension Study M20-098 in which 
all subjects will receive a 24-hour/day CSCI of ABBV-951 at individually optimized therapeutic dose 
levels.
There are no post-treatment activities except for subjects who prematurely discontinue study 
participation.  See Section 5.7 for additional information:
Study Completion
Once all randomized subjects complete the study, or prematurely discontinue, the database will be 
locked.  The blind will be broken and the data will be analyzed by the sponsor according to a 
prespecified statistical analysis plan (SAP).
4.2 Discussion of Study Design
Choice of Control Group
Carbidopa/levodopa remains the standard of care for PD.
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be used in this study.  All efficacy 
measurements are qualified for assessing disease activity in subjects with PD.
Page 18 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Suitability of Subject Population
The subject population will consist of subjects with aPD who report motor fluctuations that are 
inadequately controlled by their current PD treatment and who experience a daily average of at least 
2.5 hours of "Off" time (with a minimum of 2 hours each day) as assessed by PD diaries completed in 
3 consecutive days prior to V2.
Rationale for Selection of Therapeutic Dose Range
It is recognized that the treatment of PD is highly individualized; both the treatments administered and 
their doses are often customized, based on the patients' signs and symptoms and their response to
medication.  This results in a wide distribution of therapeutic doses, in clinical practice and in clinical 
trials.
Previous data from LCIG suggest that LD doses could range from less than 700 mg/day to approximately 
4260 mg/day, over a 24-hour daily treatment period.  This is equivalent to approximately 1000 to
6000 mg LDP per day, which was selected as the range of possible ABBV-951 daily doses for the study.
Loading Dose for Study Drug Solution
The volume of the loading dose for study drug solution will be calculated based on the volume of 
ABBV-951 delivering an amount of LD equivalent to the number of CD/LD 25/100 IR tablets taken as the 
first dose of the day at the end of the Oral CD/LD Stabilization Period, as presented in Table 1.  The 
loading dose solution will be delivered subcutaneously via the pump on Day 1 only.  After delivery of the 
loading dose on Day 1, this function will be disabled by the investigator or designee for the remainder of 
the study by adjusting the loading dose volume to 0.00 mL.
Table 1.
Infusion Loading Dose Determination
LD from First Morning Dose of CD/LD IR 
at End of Stabilization Period (mg)
Infusion Loading Dosea (mL)
Approximate Duration of 
Loading Dose (minutes)
100
0.6
6 
200
1.1
12 
300
1.6
18
≥ 400
2.2
24 
CD/LD = carbidopa/levodopa; IR = immediate release; LD = levodopa; LDP = levodopa phosphate
a.
Based on the ABBV-951 concentration of LDP 240 mg/mL and molecular weight conversion factor 100 mg LD = 141 mg 
LDP.
Continuous Infusion Rates
ABBV-951 or placebo solution will be delivered continuously (24 hours/day) via an infusion set 
connected to a pump designed for ambulatory use.  Each subject's starting continuous infusion rate will 
be calculated based on the subject's stabilized oral CD/LD IR therapy at the end of the Oral CD/LD 
Stabilization Period and an algorithm developed following a combination of pharmacokinetic and clinical 
considerations from ABBV-951 Phase 1 studies.
Page 19 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Based on the total amount of oral LD that the subject receives during the 16-hour typical waking time at 
the end of the Oral CD/LD Stabilization Period, the starting infusion rate for ABBV-951 or placebo 
solution should be selected from Table 2, using the rates under the column heading "Starting Infusion 
Rate."  These starting continuous infusion rates are estimated for the mid-point of the LD intervals 
provided.
Table 2.
Starting Infusion Rates Determination and Limits on Continuous Infusion Rate 
During Study
Daily LD from CD/LD IR at End of Stabilization Period (mg/16 hr)a
Starting Infusion Rateb (mL/hr)
< 500
0.16
500 
0.18
600 
0.20
700 
0.24
800 
0.27
900 
0.30
1000 
0.34
1100 
0.37
1200 
0.40
1300 
0.44
1400 
0.47
1500 
0.50
1600 
0.54
1700 
0.57
1800 
0.60
1900 
0.64
2000 
0.67
2100 
0.70
2200 
0.74
Page 20 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Daily LD from CD/LD IR at End of Stabilization Period (mg/16 hr)a
Starting Infusion Rateb (mL/hr)
2300 
0.78
2400 
0.81
2500 
0.84
2600 
0.88
2700 
0.91
2800 
0.94
2900 
0.98
3000 
1.00
≥ 3100
1.04c
CD/LD = carbidopa/levodopa; hr = hour; IR = immediate release; LD = levodopa; LDP = levodopa phosphate
a.
Do not subtract the first morning dose.
b.
Based on the ABBV-951 concentration of LDP 240 mg/mL and molecular weight conversion factor 100 mg LD = 141 mg 
LDP.
c.
AbbVie Therapeutic Area Medical Director (TA MD) to be contacted; see bolded text at the end of Section 4.2.
CSCI Optimization
The ABBV-951 or placebo solution infusion rate may be adjusted at the investigator's discretion only 
during the CSCI Optimization Phase.
Achieving and maintaining an optimal therapeutic response for the individual subject means maximizing 
the functional "On" time during the day by minimizing the number and duration of "Off" episodes 
(bradykinesia) and minimizing "On" time with troublesome dyskinesia.  The infusion pump allows the 
infusion rate to be increased or decreased by multiples of 0.01 mL/hour which, for the ABBV-951 
solution, correspond to approximately 1.7 mg LD/hour.  The minimum infusion rate must be at least 
0.15 mL/hour, and the maximum infusion rate cannot exceed 1.04 mL/hour.  Under no circumstances 
can infusion rates be set below 0.15 mL/hour or above 1.04 mL/hour.
Conversion Algorithm
The conversion algorithm was created taking into consideration the molecular weight of LDP, drug 
product concentration, pharmacokinetic data, and clinical considerations from ABBV-951 Phase 1 
studies.
Assumptions Used to Generate the Algorithm
From pharmacokinetic studies, a conversion factor of oral levodopa to LDP was determined to be 1.41 
based on differences in molecular weight.  One milliliter of the ABBV-951 drug product used in this study 
contains 240 mg of LDP and 12 mg of CDP.
Most PD patients are treated with oral PD medications during their waking time (typically 16-hour/day 
treatment period).  Once the amount of LDP needed over the 16-hour period has been calculated, it is 
divided by 240 mg to determine the number of milliliters needed over the 16-hour period, and then 
Page 21 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
divided over 16 hours to establish the hourly infusion rate.  ABBV-951 is meant to be administered over 
24 hours daily, so once the hourly infusion rate is established, the treatment period is extended for the 
additional 8 hours to account for nighttime treatment.
Note:  Should the daily LD from CD/LD IR at the end of the Oral CD/LD Stabilization Period for a 
subject be estimated to be ≥ 3100 mg, which is equivalent to > 6000 mg LDP/day (i.e., requiring an 
infusion rate > 1.04 mL/hour), the investigator should contact the AbbVie TA MD to discuss the 
subject's levodopa responsiveness, clinical status, and subsequent study drug dosing. Under no 
circumstances are infusion rates > 1.04 mL/hour allowed.
5 STUDY ACTIVITIES
5.1 Eligibility Criteria
All subjects will be evaluated to ensure they meet the eligibility criteria during the Screening Period, 
prior to entering the Oral CD/LD Stabilization Period, and prior to randomization on Day 1 (V6).  Subjects 
must meet all eligibility criteria prior to the Oral CD/LD Stabilization Period and the administration of 
open-label CD/LD IR tablets at V3.  Subjects must continue to meet these eligibility criteria prior to 
randomization (V6) and administration of blinded study drug.
Consent
1. Subject must be able to understand the nature of the study and have had the opportunity to 
have any questions answered by the investigator.
2. Subject, if judged by the investigator to have decision-making capacity, must voluntarily sign 
and date an informed consent form approved by an independent ethics committee 
(IEC)/institutional review board (IRB) prior to initiation of any study-specific procedures.
Demographic and Laboratory Assessments
3. Subject must be male or female, 30 years of age or older at Screening (V1).
4. Subject is willing and able to comply with procedures required in this protocol.
5. Subject does not have a low vitamin B12 level (< 200 pg/mL); or does not have low-normal 
vitamin B12 level (< 300 pg/mL) with elevated methylmalonic acid (MMA > 0.41 µmol/L) at V1.a
6. Subject has normal cognitive function (Mini-Mental State Examination [MMSE] score of 24 or 
greater).
7. Subject is considered to be a suitable candidate to receive ABBV-951 and subject (or
caregiver, if applicable) demonstrates the understanding and correct use of the delivery system, 
including the insertion of the cannula into the subject's abdomen, as assessed by the 
investigator or designee during the Screening Periodb and at V5.c
Page 22 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Disease Activity
8. Subject must have a diagnosis of levodopa-responsive idiopathic PD and the total daily dose 
of LD equivalents from LD-containing medication and COMT inhibitors must be ≥400 mg.
9. Subject must have recognizable/identifiable "Off" and "On" states (motor fluctuations) as 
established through investigator observation and confirmed by PD Diary entries recorded during 
the concordance test performed during the Screening Period.
10. Subject must be judged to be inadequately controlled by current therapy in the 
investigator's opinion and experience a minimum daily average of 2.5 hours of "Off" time (with a 
minimum of 2 hours of "Off" time each day) as assessed by PD Diary for 3 consecutive days prior 
to V2d and maintain at least 2 hours of "Off" time each day for 3 consecutive days before V6
(Randomization Visit).e
11. Subject 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.
Subject History
12. Subject does not have a history of significant skin conditions or disorders (e.g., psoriasis, 
atopic dermatitis) or evidence of recent sunburn, acne, scar tissue, tattoo, open wound, 
branding, or colorations that in the investigator's opinion would interfere with the infusion of 
study drug or could interfere with study assessments.f
13. Subject does not have a recent (within 6 months prior to screening [V1]) history of drug or 
alcohol abuse that could preclude adherence to the protocol in the investigator's opinion.
14. Subject does not have significant suicidal ideation currently or within 1 year prior to 
screening (V1) as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation 
portion of the C-SSRS, or any history of suicide attempts within the last 2 years.
15. Subject does not have a history or presence of psychotic episodes that in the investigator's 
judgment are not adequately controlled by second-generation (atypical) antipsychotics and that 
could preclude adherence to the protocol.
16. Subject does not have other clinically significant unstable medical conditions or any other 
reason that the investigator determines would interfere with the subject's participation in this 
study or would make the subject an unsuitable candidate to receive study drug.
17. Subject does not have a history of allergic reaction or significant sensitivity to levodopa or 
constituents of the study drug (and its excipients) and/or other products in the same class.
18. Subject agrees to receive CD/LD IR and has no known medical condition for which levodopa 
is contraindicated (e.g., suspicious undiagnosed melanoma, narrow-angle glaucoma, severe 
heart failure, severe cardiac arrhythmia, pheochromocytoma, untreated hyperthyroidism, or 
Cushing's syndrome and other circumstances where adrenergics are contraindicated).
19. Subject has not donated or lost 550 mL or more blood volume (including plasmapheresis) or 
received a transfusion of any blood product within 8 weeks prior to Screening (V1).
Page 23 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
20. Subject has no known active COVID-19 infection.  Subject must not have signs/symptoms 
associated with COVID-19 infection or known exposure to a confirmed case of COVID-19 
infection during 14 days prior to Screening.

Subjects who do not meet COVID-19 eligibility criteria must be screen failed and may only 
rescreen after they meet the following COVID-19 viral clearance criteria:

Symptomatic subjects:  At least 2 negative viral tests in a row, ≥ 24 hours apart after at 
least 10 days have passed since recovery, defined as resolution of fever without use of 
antipyretics and improvement in respiratory symptoms (e.g., cough, shortness of 
breath)

Asymptomatic subjects:  At least 2 negative viral tests in a row, ≥ 24 hours apart after at 
least 10 days have passed since prior positive result (Note:  subjects who develop 
symptoms will follow guidance above for symptomatic subjects)

Frequency or timing of COVID-19 testing and interval between testing for the above viral 
clearance criteria may be adjusted to account for epidemiological trends, updated 
information regarding infectivity and local/institutional guidelines.
Contraception
21. If female of childbearing potential, subject must have a negative serum pregnancy test at V1, 
and a negative urine pregnancy test at V3 prior to start of the Oral CD/LD Stabilization Period 
and a negative urine pregnancy test on Day 1 (V6) prior to randomization.  Female subjects of 
non-childbearing potential (either postmenopausal or permanently surgically sterile as defined 
in Section 5.2) at V1 do not require pregnancy testing.
22. If female, subject must be either postmenopausal, OR permanently surgically sterile OR for 
women of childbearing potential practicing at least 1 protocol-specified method of birth control
that is effective from V3 through at least 30 days after the end of study drug administration (end 
of Double-Blind Treatment Period).
23. If male and sexually active with female partner(s) of childbearing potential, subject must 
agree to practice protocol-specified contraception from V3 through 30 days after the end of 
study drug administration.
24. If female, subject is not pregnant, breastfeeding, or considering becoming pregnant or 
donating eggs during the study or within 30 days after the end of study drug administration.
25. If male, subject is not considering fathering a child or donating sperm during the study or 
within 30 days after the end of study drug administration.
Concomitant Medications
26. Subject has not received an investigational product within a time period equal to 5 half-lives, 
if known, or within 6 weeks, whichever is longer, prior to randomization.
a.
Subjects with a low vitamin B12 or low-normal vitamin B12 and high MMA plasma level may undergo supplemental vitamin 
therapy.  A retest for vitamin B12 is allowed during the Screening Period without repeating other screening procedures.
Page 24 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
b.
Subjects who do not meet the demonstration of understanding and correct use of the delivery system criterion at V2 may 
repeat the assessment once (without repeating other screening procedures) at an unscheduled visit prior to the start of the 
Oral CD/LD Stabilization Period (V3). If the criterion is still not met, subjects must be screen failed.
c.
Subjects who do not meet the demonstration of understanding and correct use of the delivery system criterion at V5 must 
be prematurely discontinued from the study.
d.
Subjects must experience an average daily "Off" time of at least 2.5 hours over 3 consecutive PD Diary days and a minimum 
of 2 hours each day prior to V2 to remain eligible for the study.  The PD Diaries used for this evaluation must have at least 
44 of the 48 daily entries completed. Subjects who fail to meet this requirement prior to Visit 2 may repeat the PD Diary for 
3 additional consecutive days prior to V3. If the "Off" time criterion is still not met, subjects must be screen failed.
e.
Subjects who do not meet the required minimum of at least 2 hours of "Off" time each day for 3 consecutive days before V6 
(Randomization Visit) must be prematurely discontinued from the study.  The PD Diaries used for this evaluation must have 
at least 44 of the 48 daily entries completed.
f.
Subjects with evidence of transient skin conditions such as recent sunburn or open wound that resolved prior to V6 are 
eligible for randomization.
5.2 Contraception Recommendations
Contraception Requirements for Females
Subjects must follow the following contraceptive guidelines as specified:

Females, Non-Childbearing Potential
Females of non-childbearing potential do not need to use birth control during or following study 
drug treatment if considered to be of non-childbearing potential due to meeting any of the 
following criteria:

Postmenopausal, age > 55 years with no menses for 12 or more months without an 
alternative medical cause.

Postmenopausal, age ≤ 55 years with no menses for 12 or more months without an 
alternative medical cause AND a follicle-stimulating hormone (FSH) level > 40 IU/L.

Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or 
hysterectomy).
Females, of Childbearing Potential

Females of childbearing potential must avoid pregnancy during the study and for at least 
30 days after the end of study drug administration.  Females of childbearing potential must 
commit to one of the following methods of birth control:

Combined (estrogen and progestogen containing) hormonal birth control (oral, 
intravaginal, transdermal, injectable) associated with inhibition of ovulation initiated at 
least 30 days prior to V6.

Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 30 Days prior to V6.

Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a 
hysterosalpingogram confirms success of the procedure).

Intrauterine device (IUD).
Page 25 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Intrauterine hormone-releasing system (IUS).

Vasectomized partner (provided the partner has received medical confirmation of the 
surgical success of the vasectomy and is the sole sexual partner of the trial subject).

Practice true abstinence, defined as:  Refraining from heterosexual intercourse when 
this is in line with the preferred and usual lifestyle of the subject (periodic abstinence 
[e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are 
not acceptable).
Contraception recommendations related to use of concomitant therapies prescribed should be based on 
the local label.
Contraception Requirements for Males
Male subjects, including those who have undergone a successful vasectomy, who are sexually active 
with a female partner of childbearing potential must agree to the following from V3 through at least 
30 days after the end of study drug administration:

Use condoms.
AND

His female partner(s) must also use at least 1 of the following methods of birth control:

Combined (estrogen and progestogen containing) hormonal birth control (oral, intravaginal, 
transdermal, injectable) associated with inhibition of ovulation initiated at least 30 days 
prior to V6.

Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 30 days prior to V6.

Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a hysterosalpingogram 
confirms success of the procedure).

IUD.

IUS.
5.3 Prohibited Medications and Therapy
The medications listed in Table 3 are prohibited during the Oral CD/LD Stabilization Period and the 
Double-Blind Treatment Period.
Page 26 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Table 3.
Prohibited Medications
Apomorphinea
Levodopa-carbidopa intestinal gel (LCIG)/carbidopa-levodopa enteral suspension (CLES)
Dopamine-depleting agents (e.g., reserpine, tetrabenazine, amphetamines)
MAO-A inhibitors and non-selective MAO inhibitorsb
Ergot dopamine agonists (e.g., lisuride, bromocriptine, cabergoline)
Dopamine antagonist or partial agonist, first generation antipsychotics, or antiemetic medications that 
interact with brain dopamine receptors (e.g., fluphenazine, loxapine, perphenazine, thiothixene, haloperidol, 
metoclopramide, aripiprazole, asenapine)
Oral and/or inhaled medications containing levodopac
COMT inhibitors (e.g., entacapone, tolcapone, opicapone)d
CD/LD = carbidopa/levodopa; COMT = catechol-O-methyltransferase; IR = immediate release; MAO-A = monoamine oxidase A
a.
Apomorphine injection is allowed as a rescue medication during the Screening Period; it must be discontinued prior to 
starting Oral CD/LD Stabilization Period study drug and is prohibited for the remainder of the study.
b.
Non-selective MAO inhibitors are contraindicated for use with levodopa and should not be taken by study subjects.  MAO
inhibitors with selectivity for MAO type B (e.g., rasagiline, selegiline, safinamide) are allowed.
c.
Allowed during the Screening Period; must be discontinued prior to starting Oral CD/LD Stabilization Period study drug and 
is prohibited for the remainder of the study.  CD/LD IR provided for the study is allowed in case of serious sudden medical 
need as rescue medication.
d.
Allowed during the Screening Period; must be discontinued prior to starting Oral CD/LD Stabilization Period study drug and 
is prohibited for the remainder of the study.
5.4 Prior and Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins and/or herbal 
supplements) that the subject is receiving from 30 days prior to Screening (V1) or receives during the 
study must be recorded through the end of the study.
Any questions regarding concomitant or prior therapy should be raised to the AbbVie sponsor contact or 
emergency medical contact.  Information regarding potential drug interactions with ABBV-951 is located 
in the ABBV-951 Investigator's Brochure.1
With the exception of the Oral CD/LD Stabilization Period and the CSCI Optimization Phase, subjects 
should remain on stable PD medication for the duration of the study, unless medically needed.
All subjects will be provided with oral CD/LD 25/100 IR tablets in case rescue therapy is needed during 
the Double-Blind Treatment Period.  Once blinded study drugs have been initiated, rescue tablets should 
only be used in the case of a serious medical need, such as rapid deterioration of motor symptoms.  The 
subject should be instructed to record, in the Subject Dosing Diary, all oral CD/LD IR tablets taken as 
rescue medication during the Double-Blind Treatment Period (i.e., not only 3 consecutive days prior to 
study visits).
The following concomitant (Table 4) and rescue (Table 5) medications are allowed:
Page 27 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Table 4.
Allowed Concomitant Medications/Therapy
Allowed Concomitant Medications/Therapy
Non-ergolinic dopamine agonistsa (e.g., pramipexole, ropinirole, rotigotine)
Selective MAO-B inhibitors (e.g., rasagiline, selegiline)
Amantadine (IR and ER formulations)
Safinamide
Istradefylline
ER = extended release; IR = immediate release; MAO = monoamine oxidase
a.
Apomorphine and ergot dopamine agonists (e.g., lisuride, bromocriptine, cabergoline) are NOT allowed.
Table 5.
Allowed Rescue Medications/Therapy
Rescue Concomitant Medications/Therapy
Comments/Notes
CD/LD 25/100 IR
Allowed as rescue therapy (e.g., in the event of a serious medical 
need, such as rapid deterioration of motor symptoms).  Half 
tablets are allowed.
25/100 = 25 mg/100 mg; CD/LD = carbidopa/levodopa; IR = immediate release
5.5 Withdrawal of Subjects and Discontinuation of Study
A subject may voluntarily withdraw or be withdrawn from the study at any time for reasons including, 
but not limited to, the following:

Clinically significant abnormal laboratory results or AEs, which rule out continuation of the study 
drug, as determined by the investigator or the AbbVie TA MD.

The investigator believes it is in the best interest of the subject.

The subject requests withdrawal from the study.

Eligibility criteria violation was noted after the subject started study drug and continuation of 
the study drug would place the subject at risk.

Introduction of prohibited medications or dosages and continuation of the study drug would 
place the subject at risk.

The subject becomes pregnant while on study drug.

Subject is significantly noncompliant with study procedures, which would put the subject at risk 
for continued participation in the trial.

Subject answers "yes" to Questions 4 or 5 on the C-SSRS; these subjects should be referred for 
appropriate follow-up care.
Page 28 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the subject's final status.  At a minimum, 2 telephone calls must be made and 1 certified 
letter must be sent and documented in the subject's source documentation.
AbbVie may terminate this study prematurely, either in its entirety or at any site.  The investigator may 
also stop the study at his/her site if he/she has safety concerns.  If AbbVie terminates the study for 
safety reasons, AbbVie will promptly notify the investigator.
The investigator should contact the sponsor emergency medical contact before discontinuing a subject 
from the study for a reason other than "planned per protocol," to ensure all acceptable mitigation steps 
have been explored.
COVID-19 Pandemic-Related Acceptable Protocol Modification
During the COVID 19 pandemic, it has been necessary to employ mitigation strategies to enable the 
investigator to ensure subject safety and continuity of care.  Acceptable mitigation strategies are 
identified and included in the Operations Manual in Appendix F.
Refer to the Operations Manual in Appendix F for details on how to handle study activities/procedures.
5.6 Temporary Suspension of Study Drug Treatment
If a pump malfunction causes blinded study drug infusion to stop, subjects must simultaneously stop 
administration of blinded oral study drug capsules and contact the site.  Subjects should take open-label
CD/LD IR tablets at the regimen established during the Oral CD/LD Stabilization Period until infusion of 
blinded study drug solution can be resumed, at which time oral dosing of blinded study drug capsules 
should also be resumed. Half tablets of CD/LD IR are not allowed in this situation.
A subject's blinded study drug treatment may need to be temporarily suspended for medical reasons 
(e.g., illness, hospitalization).  If such a situation occurs, subjects who experience a suspension up or 
equal to 3 days in duration may be reinitiated on blinded study drug at the investigator's discretion.  If 
blinded study drug is suspended for more than 3 days, approval from the AbbVie TA MD is required prior 
to blinded study drug being restarted.
5.7 Follow-Up After Subject Discontinuation of Study Drug or Study
If a subject prematurely discontinues study drug during the open-label Oral CD/LD Stabilization Period, a 
follow-up visit or phone call will be completed 30 days after the last dose of study drug, if the subject is 
willing, to ensure all treatment-emergent AEs/SAEs have been resolved.
If a subject prematurely discontinues blinded study drug, the procedures outlined for V13 (also the 
Premature Discontinuation Visit for the Double-Blind Treatment Period) should be completed as soon as 
possible, preferably within 2 weeks.  To minimize missing data for efficacy and safety assessments, 
subjects will continue study participation to be followed for all regularly scheduled visits, unless subjects 
have decided to discontinue study participation entirely.  Subjects should be advised on the continued 
scientific importance of their data even if they prematurely discontinue treatment with blinded study 
drug.  If a subject discontinues study participation during the Double-Blind Treatment Period or 
Page 29 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
completes the study but will not participate in the extension Study M20-098 and is willing, a follow-up 
visit or phone call 30 days after the end of study drug administration will be completed to ensure all 
treatment-emergent AEs/SAEs have resolved.  If a subject prematurely discontinues study participation
and withdraws informed consent, no further attempt to contact the subject will be made.
Only subjects who complete the 12-week double-blind study drug and study visits through V13 are 
eligible for the extension Study M20-098.  For subjects who enroll in the extension study, 
Study M15-736 activities end with V13 and there is no follow-up visit or phone call.
5.8 Study Drug and Study Devices
The investigational product in this study consists of ABBV-951 (solution for infusion) and study devices.  
Additional study drug includes placebo for ABBV-951 (solution for infusion), the comparator drug (CD/LD 
IR), placebo for the comparator drug, and open-label CD/LD IR.  Although this is not an investigational 
device trial and some of the devices are approved in some countries in which the study will be 
conducted, they will be labeled for investigational use.
Information for the ABBV-951 formulation and devices to be used in this study is presented in Table 6
and Table 7, respectively.
Table 6.
Identity of Study Drug
Study Period
Study Drug
Dosage Form
Deliverable 
Content
Manufacturer
Oral CD/LD Stabilization 
Period (open-label) and 
rescue during Double-Blind 
Treatment Period
CD/LDa
Tablet/Oral
25/100 mg
Generic 
manufacturer
Double-Blind Treatment 
Period
ABBV-951 
12/240 mg/mL 
(CDP4'/LDP4') 
S.INF. 10 mL vial
Solution for 
infusion/SC
120 mg/2400 mg 
(CDP4'/LDP4')
AbbVie
Placebo solution 
for ABBV-951 
10 mL vial
Solution for 
infusion/SC
NA
AbbVie
CD/LDa
Over-
encapsulated 
tablet/Oral
25/100 mg
Generic 
manufacturer; 
over 
encapsulation by 
AbbVie
Placebo for CD/LD 
IR
Capsule/Oral
NA
AbbVie
CD/LD = carbidopa/levodopa; CDP4’ = carbidopa phosphate four prime; IR = immediate release; LDP4’ = levodopa phosphate 
four prime; S.INF. = solution for infusion; SC = subcutaneous
a.
All CD/LD tablets are immediate release.
Page 30 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Table 7.
Identity of Study Devices
Description
Usage
Manufacturer
Model Number
Infusion Pump
and its 
accessories
Delivery of ABBV-951 or 
placebo solution
Phillips - Medisize 
Corporation
Phillips-Medisize - Parkinson's Disease 
Subcutaneous (PM-PDSC)
Reference # 70000042
Syringe without 
needle
Delivery of ABBV-951 or 
placebo solution
B.Braun Medical Inc.
Omnifix™syringe, luer lock, 10 mL; 
B Braun Medical reference #:
4617100V-02 (US)
Infusion Set
Delivery of ABBV-951 or 
placebo solution
Unomedical 
A ConvaTec Company
Neria™ Guard infusion set, 6 mm 
cannula, 60 cm tubing;
Unomedical reference #:
704060-5226 USA (US)
Neria™Guard infusion set, 9 mm 
cannula, 60 cm tubing;
Unomedical reference#:
704060-5229 USA (US)
Vial adapter
Facilitates transfer of 
ABBV-951 or placebo 
solution to 
syringe/reservoir
West Pharmaceutical 
Services
West Item ID:  36098056; 
Medimop Cat #:  8073005
US = United States
Note:  All devices described above are part of the PM-PDSC Delivery System.
Selection of Doses in the Study
Open-label CD/LD 25/100 IR tablets will be taken orally over 24 hours and each subject's dose will be 
individually optimized for a 24-hour daily treatment during the Oral CD/LD Stabilization Period.

The oral doses of CD/LD IR tablets and other permitted PD medications should be adjusted to 
achieve a stable clinical response for the individual subject, with the goal of maximizing the 
functional "On" time during the day by minimizing the number and duration of "Off" episodes 
(bradykinesia) and minimizing "On" time with troublesome dyskinesia.
A CSCI of ABBV-951 or placebo solution (double-blind) will be administered subcutaneously during the 
Double-Blind Treatment Period, delivered 24-hour/day via an infusion set connected to a pump 
designed for ambulatory use.

Each subject's starting infusion rate will be calculated based on the dose of total LD that the 
subject receives at the end of the Oral CD/LD Stabilization Period, normalized to a 16-hour 
waking time, and an algorithm validated with Phase 1 studies.

Infusion rates will range from 0.15 to 1.04 mL/hour.

The infusion rate may be adjusted to an optimal clinical response for the individual subject,
which means maximizing the functional "On" time during the day by minimizing the number and 
Page 31 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
duration of "Off" episodes (bradykinesia) and minimizing "On" time with troublesome 
dyskinesia.
Encapsulated CD/LD 25/100 IR tablets or placebo capsules (double-blind) will be taken orally 
24-hour/day and will follow the same administration schedule used for the oral CD/LD 25/100 IR at the 
end of the Oral CD/LD Stabilization Period.
Subject dosing will be recorded in a Subject Dosing Diary for 3 consecutive days prior to any study visit 
as specified in the study activity schedule in Appendix D.  In case of sudden deterioration of clinical 
condition, rescue tablet(s) of CD/LD IR may be taken.  Subjects will be instructed to record, in the 
Subject Dosing Diary, all oral CD/LD IR tablets taken as rescue medication during the Double-Blind 
Treatment Period (i.e., not only 3 consecutive days prior to study visits).
If a subject is unable to come to the study site to pick up study drug due to COVID-19, a direct-to-patient 
(DTP) study drug shipment can be made from study site to the subject if allowed by local regulations.  
AbbVie will submit any required notifications to the regulatory authority as applicable.  Refer to the 
Operations Manual in Appendix F for details on DTP shipment of study drug.
Device
The Phillips-Medisize Parkinson's Disease Subcutaneous (PM-PDSC) pump comes in a package that 
includes the pump, a pump carrying accessory, rechargeable batteries, and charging station. Detailed 
instructions for use (IFUs) will be provided to clinical study personnel for programming the pump, to 
subjects for using the PM-PDSC Pump Delivery System to administer the solution for infusion, and to 
subjects for preparing study drug.  Detailed IFUs will also be provided to subjects for using carrying 
accessories, the infusion set, the vial adapter, and the battery charging station.
The investigator or designee is required to disable the alternative infusion rates (Low and High infusion 
rates) and extra dose functionalities available on the PM-PDSC pump for Study M15-736.  These 
functionalities are disabled by programming the Low and High rates to be the same as the Base rate and 
setting the extra dose volume as "0.00."  After delivery of the loading dose on Day 1, this pump function 
will also be disabled by the investigator or designee for the remainder of the study by adjusting the 
loading dose volume to 0.00 mL.
The site is required to hand write the expiry date generated by the IRT system on the pump label when
the pump is dispensed to a subject.
Treatments Administered
Oral CD/LD Stabilization Period (V3, optional V4, V5)
Beginning the morning after V3, subjects will take their regimen of CD/LD 25/100 IR tablets, converted 
from all LD-containing oral medications and COMT inhibitors, as specified in Table 8, in order to 
standardize their dosing regimen and be compatible with the oral study drug to be taken during the 
Double-Blind Treatment Period.
Page 32 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Table 8.
Guidance for Conversion from LD-Containing Medications to CD/LD IR
Medication
Multiplying Factors to Calculate LD Equivalents
Immediate-release levodopa 
(e.g., Sinemet IR)
No adjustment needed (e.g., multiply by 1).
Sustained-release levodopa 
(e.g., Sinemet CR)
For subjects taking sustained-release levodopa, multiply their daily dose of 
sustained-release levodopa by 0.75 to obtain their LD IR equivalent.
Extended-release levodopa 
(Rytary)
For subjects taking extended-release levodopa, multiply their total daily dose 
of Rytary by the appropriate conversion ratio in the following table to obtain 
their LD IR equivalent.
Rytary Dose Range (mg)
Conversion Ratio (Rytary to LD Equivalent)
0 – 855
0.42
856 – 1755
0.48
1756 – 2340
0.56
≥ 2341
0.67
  
Medication
Correction Factor for COMT inhibitors
COMT inhibitors: entacapone 
(e.g., Comtan or Stalevo) or 
tolcapone (Tasmar) or 
opicapone (Ongentys)
If subjects are taking tolcapone, entacapone, or opicapone concomitantly, the 
sum of all LD equivalents calculated thus far must be multiplied by 1.33.
Note:  The levodopa dose contained in Stalevo counts as IR.
CD = carbidopa; CR = sustained release; COMT = catechol-O-methyltransferase; IR = immediate release; LD = levodopa
Note:  The conversion factors provided are based on data from the literature.2,3
The correction factor must be applied to the sum of LD equivalents calculated from all levodopa-
containing formulations.  The levodopa contained in combined CD/LD/entacapone formulations counts 
as immediate-release and needs to be added to the LD equivalents from all other sources of levodopa 
before the sum is multiplied for the COMT inhibitors corrective factor.
The levodopa amount from all levodopa-containing formulations taken during the 16-hour waking time 
of the day should be converted to LD equivalents (i.e., equivalent amount of CD/LD IR) using the 
appropriate multiplying factor and summed. Do not consider nighttime dosing or additional 
supplemental levodopa, rescue or herbal therapies for this calculation. If COMT inhibitors are taken 
concomitantly, a correction factor should be applied to the sum of LD equivalents.
Subjects will continue to take their other allowed concomitant PD medications (e.g., dopamine agonists,
MAO-B inhibitors), which must remain unchanged. At this time, COMT inhibitors will be suspended.  
During this 14- to 21-day period, the CD/LD IR regimen will be optimized to achieve the best control of 
the subject's motor symptoms as possible.
The oral CD/LD 25/100 mg IR tablet medication schedule may accommodate nighttime treatment.  The 
CD/LD 25/100 mg IR tablets must be used whole; no split, crushed, or partial tablets may be used.
Page 33 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Randomization (Day 1 [V6])
The morning of randomization, subject will arrive in a practically defined "Off" state (i.e., no PD 
medications including CD/LD IR, dopamine agonists, MAO-B inhibitors, etc., for at least 12 hours before 
V6).  At the beginning of the visit, after the study personnel verifies that the subjects continue to meet 
the study selection criteria, subjects will be randomized 1:1 into one of 2 treatment arms:

24-hour/day CSCI of ABBV-951 plus oral placebo capsules for CD/LD IR
OR

24-hour/day CSCI of placebo solution for ABBV-951 plus oral encapsulated CD/LD IR tablets
Subjects will receive their study drugs, pump, infusion system, and ancillary devices, and immediately 
begin the CSCI Optimization Phase after completion of the pre-dose assessments, as indicated in 
Appendix D.
CSCI Optimization Phase (V6, V7, V8, V9, Optional V10, V11)

In a blinded fashion, subjects will receive a dual loading dose with both oral study drug and
study drug solution.

For the oral loading dose, the number of study drug capsules will be identical to the number of 
CD/LD IR tablets taken as the first dose of the day at the end of the Oral CD/LD Stabilization 
Period.

For the loading dose solution, the volume of study drug solution will be calculated based on the 
volume of ABBV-951 delivering an amount of LD equivalent to the number of CD/LD IR tablets 
taken as the first dose of the day at the end of the Oral CD/LD Stabilization Period, and will be 
delivered subcutaneously via the pump (Table 1).

After the dual loading doses, subjects will start the continuous infusion of blinded study drug 
solution.  The infusion rate of ABBV-951/placebo solution will be calculated based on the 
subject's LD dose over the 16-hour/day waking treatment period at the end of the Oral CD/LD 
Stabilization Period and selected from Table 2.

Concurrently, subjects will receive blinded oral study drug.  Their CD/LD IR tablets will be 
replaced with study-provided capsules, which could contain active CD/LD 25/100 mg IR or 
placebo.  The oral capsules will be taken at the same schedule as determined at the end of the 
Oral CD/L.

After delivery of the loading dose on Day 1, this pump function will be disabled by the 
investigator or designee for the remainder of the study by adjusting the loading dose volume to 
0.00 mL.

The CSCI Optimization Phase will allow for modification of the infusion rates for study drug 
solution for both treatment arms, if needed. The minimum infusion rate must be at least 
0.15 mL/hour, and the maximum infusion rate cannot exceed 1.04 mL/hour.  During this phase, 
modification of the oral study drug or concomitant PD medications will not be allowed.

The pump will be programmed by the site per the pump IFU for clinical study personnel.

After 4 weeks, the subject will enter the Maintenance Phase.
Page 34 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Maintenance Phase (Day after V11 through V13)

Subjects should maintain a stable treatment regimen of their optimized randomized regimens 
and other concomitant medications, including any allowed PD medications that are still being 
administered.

Adjustments of concomitant PD medications will not be allowed unless considered medically 
necessary, for safety reasons.

At any time, subjects may take open-label CD/LD IR tablet(s) as rescue medication to address 
immediate, serious medical needs, such as the rapid deterioration of motor symptoms.  Subjects 
will be instructed to record, in the Subject Dosing Diary, all oral CD/LD IR tablets taken as rescue 
medication during the Double-Blind Treatment Period.
CSCI Optimization Phase and the Maintenance Phase
The ABBV-951/placebo solution will be self-administered by the subject or by a caregiver (if applicable) 
using study devices (i.e., infusion set connected to an infusion pump) indicated for subcutaneous 
delivery.  The PM-PDSC Pump Delivery System will need to be loaded with the study drug solution with 
the same cadence every day (e.g., every morning for subjects who require 1 vial per day; after breakfast 
and before dinner, or every 12 hours, for subjects who require 2 vials per day; before breakfast, after 
lunch and before bedtime, for subjects who require 3 vials per day).  Study drug solution will be loaded 
into a syringe that will then be placed in the pump.  When vials are changed, depending on how long the 
infusion set has already been in use, subjects may need to either change just the syringe (using a new 
vial and vial adapter) or change the syringe and use a new infusion set (i.e., infusion set tubing and 
insertion device/cannula pad, which could be used for up to 3 consecutive days when the drug is infused 
continuously).
The infusion should be administered at least 5 cm (or 2 inches) away from the umbilicus and 2.5 cm (or 
1 inch) from the previous infusion site.  Infusions should also be administered at least 5 cm (2 inches) 
away from areas of scarred or hardened tissue or stretch marks, skin folds or creases where the body 
naturally bends, or areas where clothing might cause irritation (e.g., near the beltline).
The investigator will select the length of the infusion set cannula among those provided, considering
individual subject characteristics such as thickness of the abdominal subcutaneous fat tissue. The 
appropriate cannula will be long enough to deliver study drug solution to the subcutaneous tissue 
without infiltrating the muscle wall, which can cause pain and/or occlusion of the cannula.
The infusion set and the infusion site (area of the skin where the subcutaneous cannula is inserted) may
be left unchanged for up to 3 days when the drug is infused continuously.  This includes maintaining the 
same infusion set when using a new vial; however, a new vial adapter and a new syringe are required 
any time a new vial is used.
Note: Investigators should consider instructing the subject to rotate the infusion site more frequently 
than every 3 days (e.g., every 2 days or every day) if skin irritation and/or drug pooling is observed.  Each 
time the infusion site is rotated, a new infusion set is to be used.
Subjects will track infusion sites in the Infusion Site Rotation Tool to help guide their rotation pattern 
and prevent overuse of an infusion site area throughout the Double-Blind Treatment Period.
Page 35 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Infusion Interruption
If the infusion is interrupted and study drug is not administered for more than 1 hour, subjects should 
replace the infusion set and rotate the infusion site before resuming study drug administration.  No 
action is needed if the infusion pump is disconnected and study drug is not administered for less than 
1 hour (such as when changing syringes).
Under no circumstance can a single syringe be used for longer than 24 hours.
In the event of an infusion pump malfunction or other event that prevents delivery of blinded study 
drug solution for more than 1 hour, the time period during which study drug was not delivered will be 
recorded by the site, in the electronic data capture system.  Subjects should simultaneously stop 
administration of blinded oral study drug capsules and begin taking open-label CD/LD IR tablets at the 
regimen (same number of tablets and frequency of dosing as the oral study drug capsules) established 
during the Oral CD/LD Stabilization Period until infusion of the blinded study drug solution can be 
resumed. Half tablets of CD/LD IR are not allowed in this situation. The subject should call the clinical 
study personnel, so that the subject may attempt to resume the study drug infusion.  The time that the 
infusion stopped and/or malfunction will be recorded to the minute if known (otherwise, an estimated
time will be recorded).  When the infusion is resumed, the restart time will be recorded to the minute; 
no changes to the Base infusion rate are permitted; the subject will stop taking open-label CD/LD IR 
tablets and will resume oral dosing of blinded study drug capsules.
Note: Switching subjects to open label LD/CD if the infusion has been interrupted for more than 1 hour 
maintains subjects in the "On" state before restarting the continuous infusion and minimizes the risk of
unblinding.
If the study drug infusion cannot be resumed or if the investigator is concerned that the subject may not 
be able to successfully complete the study drug infusion requirements, the subject may be discontinued 
from the study.
Blinding
All study drug during the Oral CD/LD Stabilization Period and the CD/LD IR used as rescue medication 
during the Double-Blind Treatment Period will be open-label.
Study drug for the Double-Blind Treatment Period will be blinded.  Since ABBV-951 and placebo solution 
may not appear identical, the following measures are required:

All AbbVie personnel with direct oversight of the conduct and management of the study, with 
the exception of the AbbVie Drug Supply Management Team, will remain blinded to the 
treatments.

Every effort will be made to ensure study personnel, including the treating investigator, remain 
blinded. Study sites will have at least 3 distinct personnel with non-overlapping roles:

Study site personnel who provide the study drug (e.g., pharmacist or study nurse): these 
personnel must be different from the personnel who assess subjects for the safety and 
efficacy endpoints.  This staff member should be the designated contact to address any 
subject questions related to the study drug solution.  IP accountability should also be limited 
to this site staff member.
Page 36 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Treating investigators: the treating investigator or designee should assess AEs, manage the 
device (including dose changes during the CSCI Optimization Phase), perform safety 
assessments, and control the use of rescue medications.

Efficacy raters: study sites will use a separate rater (i.e., other than the site personnel who 
provide study drug or the treating investigator) to perform all in-person efficacy 
assessments (i.e., MDS-UPDRS). The infusion tubing should be completely hidden from view 
and remain hidden while the efficacy rater sees subjects. Subjects (and caregivers, if 
applicable) should be instructed not to discuss other study-related matters with the efficacy 
rater.
Note: after the CSCI Optimization Phase starts, if the treating investigators or efficacy raters
train subjects on the use of the PM-PDSC Pump Delivery System, every effort must be made to 
maintain the blind, including using training pumps for demonstration/training purposes.

Subjects (and caregivers, if applicable) will remain blinded to the subject's treatment throughout 
the study.

CD/LD IR tablets are over-encapsulated and identical in appearance to the placebo capsules.  
The over-encapsulated CD/LD IR tablets and placebo capsules are packaged identically.

ABBV-951 solution for infusion and the placebo solution for infusion will be packaged identically.
All staff may have access to interactive response technology (IRT); however, treating investigators and 
efficacy raters should not be exposed to IP contents within the kits.
To prevent functional unblinding, the following additional measures are required:

The alternative infusion rates (Low and High infusion rates) and extra dose functionalities 
designed for the PM-PDSC pump will be disabled.

Central raters will be used for the administration and assessment of the Parkinson's Disease 
Sleep Scale-2 and the Parkinson's Disease Questionnaire-39.  Central raters will not have access 
to the results of other study assessments or subjects' medical records and will not participate in 
the care or management of subjects.
The interactive response technology (IRT) will provide access to unblinded subject treatment 
information in the event of a medical emergency that requires unblinding.  The investigator is requested 
to contact the AbbVie TA MD prior to breaking the blind.  However, if an urgent therapeutic intervention 
is necessary that warrants breaking the blind prior to contacting the AbbVie TA MD, the investigator can 
directly access the IRT system via the Unblinding transaction that is available only to the investigator, 
sponsor medical monitor, and sponsor pharmacovigilance lead.  If the IRT system is unavailable, 
unblinding may occur by contacting the technical support of the IRT vendor via either phone (preferred) 
or email.  For country-specific phone numbers, please see the following website:  
https://www.endpointclinical.com/contact/.
In the event that the blind is broken before notifying the AbbVie TA MD, the AbbVie TA MD should be 
notified within 24 hours of the blind break.  The date and reason that the blind was broken must be 
conveyed to AbbVie and recorded on the appropriate eCRF.
Page 37 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Packaging and Labeling
CD/LD IR open-label tablets will be supplied in the original packaging of the generic manufacturer and 
labeled with the clinical label.
ABBV-951 and placebo solution for ABBV-951 will be supplied as solution for infusion in vials labeled in a 
blinded fashion and packaged in a carton containing 7 vials per carton.  Each vial and carton will be 
labeled as required per country requirements.  Each label must remain affixed to the vial and carton.
The over-encapsulated CD/LD IR tablets and placebo capsules for CD/LD IR will be supplied in bottles 
and labeled with the clinical label.
AbbVie will supply blinded study drug solution, blinded oral study drug, open-label CD/LD IR tablets for 
the Oral CD/LD Stabilization Period and as rescue therapy, the study pump and its accessories, 
syringe/drug reservoir, infusion sets, and vial adapters.
Storage and Disposition of Study Drug
Study drug solution must be stored under refrigeration at 2°C to 8°C (36°F to 46°F).  Study drug solution 
must be allowed to warm to room temperature in the sealed vial for 30 minutes prior to transfer to the 
drug reservoir/syringe.  Oral study drug must be stored at room temperature 15°C to 25°C (59°F to 77°F) 
and protected from light.  The investigational products are for investigational use only and are to be 
used only within the context of this study.  The study drug and devices supplied for this study must be 
maintained under adequate security and stored under the conditions specified on the label until the 
time of use or until returned to AbbVie.
Tote bags, cold packs, cooler bags, and disposal containers may be provided to study subjects.
The PM-PDSC Pump Delivery System, including the infusion pump, infusion set, vial, vial adapter, and 
syringes, must be used as indicated and training will be provided to clinical study personnel and/or a
sponsor-provided home care nurse.  See Section 3.18 of the Operations Manual (Appendix F) for 
additional information regarding PM-PDSC Pump Delivery System training.
Detailed IFUs will be provided to clinical study personnel for programming the pump, to subjects for 
using the PM-PDSC Pump Delivery System to administer the solution for infusion, and to subjects for 
preparing study drug.  Detailed IFUs will also be provided to subjects for using carrying accessories, the 
infusion set, the vial adapter, and the battery charging station.
The site is required to hand write the expiry date generated by the IRT system on the pump label when 
the pump is dispensed to a subject.
Study Drug/Study Devices Accountability
The investigator or his/her representative will verify that study drug and study devices are received 
intact and in the correct amounts.  This will be documented by signing and dating a proof of receipt or 
similar document.  A current (running) and accurate inventory of study drug and study devices will be 
maintained in the IRT system.
Subjects will be instructed to return all vials within the original vial carton at each visit; used drug vials 
will be returned with vial adapters attached. Subjects will also be instructed to return unused tablets 
Page 38 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
and capsules in the original containers at each visit.  Used syringes and used infusion sets (inserter and 
infusion set tubing) will be collected into a disposal container and returned to the study site for proper 
disposal or an alternate sponsor-approved method of disposal shall be used.  The subject will return any 
remaining unused syringes, infusion sets (inserter and infusion set tubing), and vial adapters to the site 
at the end of the study.  At the end of the study, subjects will be instructed to return the pumps, and the
sites will reconcile the pump in the IRT system.
Site personnel will review returned study drug kits, empty study drug packaging, devices, and ancillaries 
to verify compliance at each visit.  Returned study drug kits will be reconciled in IRT at each visit.  Each 
site will be responsible for maintaining drug accountability records including product description, 
manufacturer, and lot numbers for all non-investigational products (e.g., rescue therapy) dispensed by 
the site.  Returned study drug should not be re-dispensed to the subject.
See Section 3.19 of the Operations Manual (Appendix F) for additional information regarding 
dispensation and return of the PM-PDSC Pump Delivery System.
Upon completion or termination of the study, all original containers (containing unused investigational 
product) will be returned to AbbVie or destroyed on site, according to instructions from AbbVie and 
according to local regulations.
5.9 Randomization/Drug Assignment
Subject Identifier Assignment
An IRT system will assign a unique identification number to each subject at V1.  For subjects who do not 
meet the study selection criteria to be enrolled in the Oral CD/LD Stabilization Period, clinical study 
personnel must register the subject as a screen failure in the IRT system.
Treatment of study drug solution and oral study drug will be administered in a blinded manner during 
the Double-Blind Treatment Period.
Subjects who are enrolled will retain the subject number assigned to them at V1 throughout the study.  
Contact information and user guidelines for the IRT use will be provided to each site.
Selection and Timing of Dose for Each Subject
At Day 1/Randomization Visit (V6), after confirming that the subject continues to meet study selection 
criteria, the IRT will randomize the subject to receive one of the following double-blind treatments for 
12 weeks, using a 1:1 randomization ratio:

24-hour/day CSCI of ABBV-951 plus oral placebo capsules for CD/LD IR
OR

24-hour/day CSCI of placebo solution for ABBV-951 plus encapsulated CD/LD IR tablets.
A CSCI of ABBV-951 study drug or placebo solution will be delivered over 24 hours daily for up to 
12 weeks via an infusion set connected to a pump.  Each subject's starting continuous infusion rate will 
be calculated based on the subject's daily LD intake during the waking time at the end of the Oral CD/LD 
Page 39 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Stabilization Period and an algorithm developed following the analysis of pharmacokinetic data from 
Phase 1 studies.  The infusion rates might be adjusted only during the CSCI Optimization Phase.
5.10 Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol except when necessary to 
eliminate an immediate hazard to study subjects.  The investigator is responsible for complying with all
protocol requirements, written instructions, and applicable laws regarding protocol deviations.  If a 
protocol deviation occurs (or is identified, including those that may be due to the COVID-19 pandemic),
the investigator is responsible for notifying IEC/IRB, regulatory authorities (as applicable), and AbbVie.
6 SAFETY CONSIDERATIONS
6.1 Complaints and Adverse Events
Complaints
A complaint is any written, electronic, or oral communication that alleges deficiencies related to the 
physical characteristics, identity, quality, purity, potency, durability, reliability, safety, effectiveness, or 
performance of a product/device.  Complaints associated with any component of this investigational 
product must be reported to AbbVie.
Product Complaint
A product complaint is any complaint related to the biologic or drug component of the product or to the 
medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (e.g., printing illegible), missing components/product, device not working properly, 
or packaging issues.
For medical devices, a product complaint also includes:

All deaths of a subject using the device

Any illness, injury, or AE in the proximity of the device

An AE that could be a result of using the device

Any event needing medical or surgical intervention including hospitalization while using the 
device

Malfunctions, use errors, or inadequacy in the information supplied by the manufacturer
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 24 hours of the study site's knowledge of the event.  Product complaints occurring during the 
study will be followed up to a satisfactory conclusion.
Page 40 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Medical Complaints/Adverse Events and Serious Adverse Events:  Study Drug
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not the event is considered causally related to the use of the 
product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as well as from 
"special situations," such as accidental or intentional overdose, medication error, occupational or 
accidental exposure, off-label use, drug abuse, drug misuse, or drug withdrawal, all which must be 
reported whether associated with an AE or not.  Any worsening of a pre-existing condition or illness is 
considered an AE.  Worsening in severity of a reported AE should be reported as a new AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in discontinuation 
from the study, necessitate therapeutic medical intervention, and/or if the investigator considers them 
to be AEs.
The investigators will monitor each subject for clinical and laboratory evidence of AEs on a routine basis 
throughout the study.  All AEs will be followed to a satisfactory conclusion.
An elective surgery/procedure scheduled to occur during a study will not be considered an AE if the 
surgery/procedure is being performed for a pre-existing condition and the surgery/procedure has been 
pre planned prior to study entry.  However, if the pre-existing condition deteriorates unexpectedly 
during the study (e.g., surgery performed earlier than planned), then the deterioration of the condition 
for which the elective surgery/procedure is being done will be considered an AE.
If an AE, whether associated with study drug or not, meets any of the following criteria, it is to be 
reported to AbbVie clinical pharmacovigilance or the CRO (as appropriate) as an SAE within 24 hours of 
the site being made aware of the SAE (refer to Section 4.2 of the Operations Manual (Appendix F) for 
reporting details and contact information):
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had not been 
taken.  This does not include an event that would have been fatal if it 
had occurred in a more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any length 
of time or prolongs the subject's hospital stay.  This does not include 
an emergency room visit or admission to an outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that results in 
fetal loss.
Page 41 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Persistent or Significant 
Disability/Incapacity
An event that results in a condition that substantially interferes with 
the activities of daily living of a study subject.  Disability is not 
intended to include experiences of relatively minor medical 
significance such as headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle).
Important Medical Event 
Requiring Medical or Surgical 
Intervention to Prevent 
Serious Outcome
An important medical event that may not be immediately life-
threatening or result in death or hospitalization, but based on 
medical judgment may jeopardize the subject and may require 
medical or surgical intervention to prevent any of the outcomes 
listed above (i.e., death of subject, life threatening, hospitalization, 
prolongation of hospitalization, congenital anomaly, or persistent or 
significant disability/incapacity).  Additionally, any elective or 
spontaneous abortion or stillbirth is considered an important 
medical event. Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or 
drug abuse.
All AEs reported from the time of study drug administration until 30 days after discontinuation of study 
drug administration will be collected, whether solicited or spontaneously reported by the subject.  In 
addition, study procedure-related serious and nonserious AEs will be collected from the time the subject 
signs the study-specific informed consent.
AbbVie will be responsible for Suspected Unexpected Serious Adverse Reactions (SUSAR) reporting for 
the Investigational Medicinal Product (IMP) in accordance with global and local requirements.
Adverse events will be monitored throughout the study to identify any of special interest that may 
indicate a trend or risk to subjects.
Adverse Events of Special Interest
The following AESIs will be monitored during the study:

Polyneuropathy

Weight loss

Somnolence

Hallucinations/psychosis
Hallucinations, especially visual hallucinations, are a common symptom in patients with PD and could be 
associated with disease progression, comorbid pathologies, and/or concomitant medications. Older 
subjects, especially with history of hallucination and psychosis, are more at risk of exacerbating 
psychotic symptoms even if these are well-controlled with antipsychotic medications at Baseline.  
Hallucinations might be prevented by reviewing and managing psychogenic concomitant medications 
(including those for the management of PD, especially dopamine agonist) prior to enrollment in the 
Page 42 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
study.  Should hallucinations appear during the study, standard of care may be applied.  This should 
include a conservative approach of assessing alternate etiologies and addressing them as appropriate 
and if none are found, waiting a few days to see if the phenomenon resolves spontaneously.  However, 
the ultimate decision on how an individual subject is managed during the study is the decision of the 
investigator or designee.
Local tolerability will be assessed.  Infusion site evaluations will be performed at each scheduled clinic 
visit and may be performed at an unscheduled clinic visit.  Any observation of infusion site 
irritation/reaction (> 2 or > C on the infusion site evaluation scale) must be recorded as an AE.  Other 
infusion site–related reactions such as cellulitis/abscess formation, ecchymoses, subcutaneous nodules, 
or scarring should be evaluated and recorded as AEs.  An independent blinded review of moderate and 
severe infusion site–related reactions will be performed.
Adverse Event Severity and Relationship to Study Drug
The investigators will rate the severity of each AE as mild, moderate, or severe.
The investigator will use the following definitions to rate the severity of each AE:
Mild
The AE is transient and easily tolerated by the subject.
Moderate
The AE causes the subject discomfort and interrupts the subject's usual 
activities.
Severe
The AE causes considerable interference with the subject's usual activities 
and may be incapacitating or life threatening.
The investigator will use the following definitions to assess the relationship of the AE to the use of study 
drug:
Reasonable 
Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
sufficient evidence (information) to suggest a causal relationship.
No Reasonable 
Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
insufficient evidence (information) to suggest a causal relationship.
Medical Complaints/Adverse Events and Serious Adverse Events:  Study Medical Device
Adverse Event
An AE is defined as any untoward medical occurrence, unintended disease or injury or any untoward 
clinical signs (including an abnormal laboratory finding) in subjects, users or other persons whether or 
not related to the investigational medical device.
If an AE meets any of the following criteria, it is to be reported to AbbVie as an SAE within 24 hours after 
the site is made aware of the SAE:
Page 43 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Led to death, injury, or permanent impairment to a body structure of body function

Led to a serious deterioration in the health of a subject that either resulted in:

a life-threatening illness or injury, or

a permanent impairment of a body structure or a body function, or

inpatient hospitalization or prolongation of existing hospitalization, or

medical or surgical intervention to prevent life threatening illness

Led to fetal distress, fetal death, or a congenital abnormality or birth defect.
A planned hospitalization for a preexisting condition, or a procedure required by the protocol, without a 
serious deterioration in health, is not considered an SAE.
Adverse Device Effects
Adverse device effects are AEs related to the use of an investigational medical device.  This includes any 
AE resulting from insufficiencies or inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the investigational medical device.  
This includes any event that is a result of a use error or intentional abnormal use of the investigational 
medical device.
Serious Adverse Device Effects
Serious adverse device effects are adverse device effects that have resulted in any of the consequences 
characteristic of an SAE.
Device Deficiency
A device deficiency is an inadequacy of an investigational medical device related to its identity, quality, 
durability, reliability, safety, or performance.  This may include malfunctions, use error, or inadequacy in 
the information supplied by the manufacturer.
If a device deficiency meets any of the following criteria, it is to be reported to AbbVie within 24 hours 
after the site is made aware:

Any SAE

Any device deficiency that may have led to an SAE if:

suitable action had not been taken or

intervention had not been made or

circumstances had been less fortunate will be reported.

New findings/updates in relation to already reported events
Device Causality Assessment
The investigator will use the following definitions to assess the relationship of the reportable device 
event.
Page 44 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Not Related – Relationship to the device can be excluded when:

the event is not a known side effect of the product category the device belongs to or of a similar 
devices and procedures;

the event has not temporal relationship with the use of the investigational device or the 
procedures;

the serious event does not follow a known response pattern to the medical device (if the 
response pattern is previously known) and is biologically implausible;

the discontinuation of medical device application or the reduction of the level of 
activation/exposure – when clinically feasible – and reintroduction of its use (or increase of the 
level of activation/exposure), do not impact on the serious event;

the event involves a body-site or an organ not expected to be affected by the device or 
procedure;

the serious event can be attributed to another cause (e.g., and underlying or concurrent 
illness/clinical condition, an effect of another device, drug, treatment, or other risk factors);

the event does not depend on a false result given by the investigational device use for diagnosis 
when applicable;

harm to the subject are not clearly due to use error.
In order to establish non-relatedness, not all the criteria listed above might be met at the same time, 
depending on the type of device/procedures and the serious event.
Unlikely – the relationship with the use of the device seems not relevant and/or the event can be 
reasonably explained by another cause, but additional information may be obtained.
Possible – the relationship with the use of the investigational device is weak but cannot be ruled out 
completely.  Alternative causes are also possible (e.g., an underlying or concurrent illness/clinical 
condition or/and an effect of another device, drug, or treatment).  Cases were relatedness cannot be 
assessed or no information has been obtained should also be classified as possible.
Probable – the relationship with the use of the investigational device seems relevant and/or the even 
cannot reasonably explained by another cause, but additional information may be obtained.
Causal relationship – the serious event is associated with the investigational device or with procedures 
beyond reasonable doubt when:

the event is a known side effect of the product category the device belongs to or of similar 
devices and procedures;

the event has a temporal relationship with investigational device use/application or procedures;

the event involves a body site or organ that

the investigational device or procedures are applied to;

the investigational device or procedures have an effect on;
Page 45 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

the serious event follows a known response pattern to the medical device (if the response 
pattern is previously known);

the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of level of activation/exposure), 
impact on the serious event (when clinically feasible);

other possible causes (e.g., an underlying or concurrent illness/clinical condition or/and an 
effect of another device, drug or treatment) have been adequately ruled out;

harm to the subject is due to error in use;

the event depends on a false result given by the investigational device used for diagnosis, when 
applicable
In order to establish relatedness, not all the criteria listed above might be met at the same time, 
depending on the type of device/procedures and the serious event.
Pregnancy
While not an AE, pregnancy in a study subject must be reported to AbbVie within 24 hours after the site 
becomes aware of the pregnancy.  Subjects who become pregnant during the study must be 
discontinued (Section 5.5).  If a pregnancy occurs in a study subject or in the partner of a study subject, 
information regarding the pregnancy and the outcome will be collected.
In the event of pregnancy occurring in a subject's partner during the study, written informed consent 
from the partner must be obtained prior to collection of any such information.  AbbVie will provide a 
separate consent form for this purpose.  Pregnancy in a subject's partners will be collected from the 
date of initiation of the infusion through 30 days after the end of the infusion.
The pregnancy outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered an SAE and must be reported to AbbVie within 24 hours after the site becomes aware of the 
event.
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
The statistical methods provided in this protocol are focused on primary and key secondary analyses.  
Complete and specific details of the statistical analysis will be described and fully documented in the 
SAP.
The final analyses will be conducted following database lock after all subjects have completed V13
(Week 12) or prematurely discontinued.  Study sites and subjects will remain blinded to the treatment 
assignment during the Double-Blind Treatment Period for the duration of the study.
Baseline for PD Diary variables will be the average of the 3 valid diaries completed before Day –1. 
Baseline for all efficacy and safety measures, other than the PD Diary, will be defined as the last 
nonmissing observation that is before the day of randomization, with the exception of vital sign 
Page 46 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
variables which will be the average of observations if multiple measurements are obtained on the same 
day.
Postbaseline efficacy and safety measures, other than AE and infusion site evaluation, collected more 
than 1 day after the last dose of double-blind study drug will not be used for efficacy and safety analyses
because data after discontinuation of study drug may be confounded by the various PD treatments that 
the subject may be on after discontinuing study treatment.
7.2 Definition for Analysis Populations
The Oral CD/LD Analysis Set includes all subjects who received at least 1 dose of open-label CD/LD IR 
tablets during the Oral CD/LD Stabilization Period.  The Oral CD/LD Analysis Set will be used to 
summarize premature discontinuations and AEs during the Oral CD/LD Stabilization Period.
The Full Analysis Set (FAS) includes all randomized subjects who received any dose of study drug during 
the Double-Blind Treatment Period and who have baseline and at least 1 postbaseline observation for at 
least 1 efficacy assessment.  The subject will be grouped according to treatment as randomized.  The 
FAS will be used for all efficacy and baseline analyses for the Double-Blind Treatment Period.
The Safety Analysis Set consists of all subjects who received any dose of study drug during the Double-
Blind Treatment Period.  Subjects will be grouped according to treatment received regardless of 
randomization.  The safety analysis set will be used for all safety analyses for the Double-Blind 
Treatment Period.
7.3 Statistical Analyses for Efficacy
Primary Efficacy Analysis
The primary efficacy endpoint is the change from Baseline to Week 12 of the Double-Blind Treatment 
Period in average daily normalized "On" time without troublesome dyskinesia (hours).  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.  A valid diary day is defined as one that 
does not have more than 2 hours of missing data (4 or less missing 30-minute entries) for the entire 
24-hour diary.  The sum of absolute "On" times without dyskinesia and "On" times with 
non-troublesome dyskinesia collected on each valid PD Diary day will be normalized to a typical waking 
day (16 hours) to account for different sleep patterns across subjects:
Normalized "On" time without troublesome dyskinesia = (Absolute "On" time without troublesome 
dyskinesia/Awake time) × 16
and averaged over 3 consecutive diary days to obtain the average daily normalized "On" time without 
troublesome dyskinesia for each visit.
The primary analysis will utilize a mixed model for repeated measures (MMRM) and include data on 
change from baseline to each post-baseline visit in average daily normalized "On" time without 
troublesome dyskinesia obtained from PD diaries.  The model will include fixed categorical effects of 
treatment, country and visit, baseline-by-visit and treatment-by-visit interactions, and baseline as a
Page 47 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
covariate.  An unstructured variance-covariance matrix will be used.  In this analysis, missing data in 
subjects who prematurely discontinue during the Double-Blind Treatment Period will be handled in the 
MMRM model based on the missing at random assumption, and model parameters will be estimated 
using the restricted maximum likelihood method.  The primary comparison will be the contrast between 
the ABBV-951 + placebo capsules and placebo solution + CD/LD IR treatment arms at Week 12 of the 
Double-Blind Treatment Period.
Secondary Efficacy Analysis
The following key secondary and other secondary endpoints will be included in multiplicity adjustment 
of the Type I error to control the familywise error rate (FWER) at 2-side significance level of 0.05 for the 
entire study.
Key secondary endpoints:

Change from Baseline to Week 12 of the Double-Blind Treatment Period in hours of average 
daily normalized "Off" time as assessed by the PD Diary

Change from Baseline to Week 12 of the Double-Blind Treatment Period in MDS-UPDRS 
Part II score

Presence of morning akinesia at Week 12 as assessed by the PD Diary

Other secondary endpoints that are included in the FWER control:

Change from Baseline to Week 12 in hours of average daily normalized "On" time without 
dyskinesia as assessed by the PD Diary

Change from Baseline to Final Visit in PDSS-2 total score

Change from Baseline to Final Visit in PDQ-39 summary index

Change from Baseline to Final Visit in EQ-5D-5L summary index

Change from Baseline to Week 12 in median bradykinesia score (BK50) as assessed by the 
PKG wearable device

Change from Baseline to Week 12 in interquartile range of bradykinesia score (BK75-BK25) 
as assessed by the PKG wearable device

Change from Baseline to Week 12 in median dyskinesia score (DK50) as assessed by the PKG 
wearable device

Change from Baseline to Week 12 in interquartile range of dyskinesia score (DK75-DK25) as 
assessed by the PKG wearable device
Change from Baseline to Week 12 in average normalized "Off" time, MDS-UPDRS Part II score, average 
normalized "On" time without dyskinesia, and PKG variables will be analyzed using the same MMRM 
model as the primary efficacy analysis.
Change from Baseline to Final Visit in PDSS-2 total score, PDQ-39 summary index, and EQ-5D-5L
summary index will be analyzed using an analysis of covariance model with the categorical fixed effects 
of treatment and country, and baseline score as a covariate.
Page 48 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
The first morning status upon awakening at each postbaseline visit will be analyzed using a generalized 
linear mixed model with a logit link function to compare the probability of having morning akinesia
between the treatment groups.  The model will include fixed categorical effects of treatment, country 
and visit, treatment-by-visit interaction, and baseline first morning status upon awakening.  An 
unstructured variance-covariance matrix will be used.  The primary comparison for this analysis will be
the odds ratio between the ABBV-951 + placebo capsules and placebo solution + CD/LD IR groups at 
Week 12.
Sensitivity Analysis of the Primary Efficacy Analysis
A sensitivity analysis on handling missing data due to premature discontinuation will be conducted on 
the primary efficacy endpoint of change from Baseline to Week 12 in average daily normalized "On" 
time without troublesome dyskinesia.  This analysis will employ the "jump-to-reference" analytic 
approach to account for missing data in subjects who prematurely discontinue during the Double-Blind 
Treatment Period.  Details for the implementation of this approach will be described in the SAP.
Additional Efficacy Analyses
Details on other efficacy analyses will be provided in the SAP.
Subgroup Analysis for Efficacy
Subgroup analyses of the primary endpoint of change from Baseline to Week 12 of the Double-Blind 
Treatment Period in average normalized "On" time without troublesome dyskinesia will be conducted 
for the following subgroups:

Age category (< 65 years or ≥ 65 years)

Sex (male or female)

Race (white or other)

Country

Duration of PD since diagnosis (< 10 years or ≥ 10 years)

Concomitant dopamine agonist use (yes or no)

Dose category (low or high levodopa dose).  Details on how to define the dose category will be 
described in the SAP.
A subgroup analysis may not be conducted if one category of the subgroup variable comprises < 20% of 
the FAS Analysis Set.
7.4 Statistical Analyses for Safety
General Considerations
Adverse events during the Oral CD/LD Stabilization Period will be analyzed using the Oral CD/LD Analysis 
Set.  Safety analyses for the Double-Blind Treatment Period will be carried out using the Safety Analysis 
Set.  Safety will be assessed by AEs, laboratory values, vital sign measurements, ECG, C-SSRS and 
QUIP-RS.  For continuous safety outcomes, the change from Baseline will be analyzed in a descriptive 
Page 49 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
manner by treatment group and by visit.  For categorical safety outcomes, the number and percentage 
of each category will be summarized by treatment group and by visit.  Shift of laboratory values from 
Baseline to defined time points will be tabulated. Hypothesis testing will not be performed for safety 
parameters.
Analysis of Adverse Events
All AEs will be coded using the current version of the Medical Dictionary for Regulatory Activities 
(MedDRA).  The number and percentage of subjects with treatment-emergent AEs, treatment-emergent 
SAEs, AESIs, AEs with a reasonable possibility of being related to study drug, AEs leading to study drug 
discontinuation during the Double-Blind Treatment Period will be summarized by treatment group and 
will be tabulated using primary MedDRA system organ class and preferred term.  Treatment emergent 
AEs for the Oral CD/LD Stabilization Period will be defined as all events that begin or worsen on or after 
first dose of open-label CD/LD IR tables during the Oral CD/LD Stabilization Period and prior to first dose 
of blinded study drug during the Double-Blind Treatment Period.  Treatment emergent AEs for the 
Double-Blind Treatment Period will be defined as all events that begin or worsen on or after first dose of 
study drug during the Double-Blind Treatment Period.  AEs with onset on the first day of blinded study 
drug will be considered treatment-emergent for the Double-Blind Treatment Period.
Analysis of Laboratory Data
Changes from Baseline to the final value during the Double-Blind Treatment Period in continuous 
laboratory parameters will be summarized by n, mean, standard deviation, minimum value, median, and 
maximum value for each treatment group and all subjects overall for each continuous hematology, 
chemistry, and urinalysis variable.
Changes in laboratory parameters from Baseline to the final value will be tabulated using shift tables 
either by Common Terminology Criteria for Adverse Events (CTCAE) grades or categorized as low, 
normal, or high based on the normal ranges of the laboratory that performed the assay.
For each hematology, chemistry and urinalysis variable that potentially clinically significant (PCS) criteria 
are defined, a summary of the number and percentage of subjects who have at least one post-baseline 
observation that meets the PCS criterion and is more extreme than their baseline value will be provided 
for each treatment group and all subjects overall.
Analysis of Vital Signs
Change from Baseline to each planned visit and to the minimum, maximum and final value during the 
Double-Blind Treatment Period will be summarized in a descriptive manner for each treatment group 
and all subjects overall for each vital sign and weight variable.  For each variable, a summary of the 
number and percentage of subjects who have at least one post-baseline observation that meets the PCS 
criteria and is more extreme than their baseline value will be provided for each treatment group and all 
subjects overall.
Other Safety Analysis
Further details and additional safety analyses will be specified in the SAP.
Page 50 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
7.5 Interim Analysis
No interim analysis on efficacy or safety data is planned for this study.
7.6 Multiplicity Adjustment and Overall Type I Error Control
In order to control the familywise error rate at 2-side significance level of 0.05 for the entire study, a 
fixed sequence testing procedure will be used for the primary, key secondary and other secondary 
endpoints.  Only if success has been demonstrated for the primary endpoint of change from Baseline to 
Week 12 in average daily normalized "On" time without troublesome dyskinesia, will the testing proceed 
to the key secondary and other secondary endpoints in the following order:

Change from Baseline to Week 12 in hours of average daily normalized "Off" time

Change from Baseline to Week 12 in MDS-UPDRS Part II score

Presence of morning akinesia at Week 12

Change from Baseline to Week 12 in hours of average daily normalized "On" time without 
dyskinesia

Change from Baseline to Final Visit in PDSS-2 total score

Change from Baseline to Final Visit in PDQ-39 summary index

Change from Baseline to Final Visit in EQ-5D-5L summary index

Change from Baseline to Week 12 in median bradykinesia score (BK50) as assessed by the PKG 
wearable device

Change from Baseline to Week 12 in interquartile range of bradykinesia score (BK75-BK25) as 
assessed by the PKG wearable device

Change from Baseline to Week 12 in median dyskinesia score (DK50) as assessed by the PKG 
wearable device

Change from Baseline to Week 12 in interquartile range of dyskinesia score (DK75-DK25) as 
assessed by the PKG wearable device
7.7 Sample Size Determination
Assuming that the difference in change from Baseline to Week 12 in average daily normalized "On" time 
without troublesome dyskinesia is 1.86 hours between ABBV-951 + placebo capsules and placebo 
solution + CD/LD IR treatment arms, and the common standard deviation is 2.9 hours, a sample size of 
52 subjects per arm will have a 90% power to detect a statistically significant difference between the 
2 treatment arms with a 2-sided significance level of 0.05.  Approximately 130 subjects will be 
randomized assuming that approximately 20% of subjects will prematurely discontinue during the 
Double-Blind Treatment Period.  This sample size also has approximately 90% power for key secondary 
endpoints of change from Baseline in normalized "Off" time, MDS-UPDRS Part II score, and presence of 
morning akinesia.
Page 51 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
An adequate number of subjects will be enrolled in the Oral CD/LD Stabilization Period to meet the 
randomization goal of the study.
8 ETHICS
8.1 Independent Ethics Committee/Institutional Review Board 
(IEC/IRB)
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IEC/IRB for review and approval.  Approval of both the protocol and the informed 
consent form(s) must be obtained before any subject is enrolled.  Any amendment to the protocol will 
require review and approval by the IEC/IRB before the changes are implemented to the study.  In 
addition, all changes to the consent form(s) will be IEC/IRB approved.
8.2 Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, Operations Manual (Appendix F), 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(ICH) guidelines, applicable regulations, and guidelines governing clinical study conduct and the ethical 
principles that have their origin in the Declaration of Helsinki.  Responsibilities of the investigator are 
specified in 0.
In the event of a state of emergency due to the COVID-19 pandemic leading to difficulties in performing 
protocol-specified procedures, AbbVie will engage with study site personnel in an effort to ensure the 
safety of subjects, maintain protocol compliance, and minimize risks to the integrity of the study while 
trying to best manage subject continuity of care.  This may include alternative methods for assessments 
(e.g., phone contacts or virtual site visits), alternative locations for data collection (e.g., use of a local lab 
instead of a central lab), and shipping investigational product and/or supplies direct to subjects to 
ensure continuity of treatment where allowed.  Refer to the Operations Manual in Appendix F for 
additional details.  In all cases, these alternative measures must be allowed by local regulations and 
permitted by IRB/IEC.  Investigators should notify AbbVie if any urgent safety measures are taken to 
protect the subjects against any immediate hazard.
8.3 Subject Confidentiality
To protect subjects' confidentiality, all subjects and their associated samples will be assigned numerical 
study identifiers or "codes."  No identifiable information will be provided to AbbVie.
9 SOURCE DOCUMENTS AND CASE REPORT FORM 
COMPLETION
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be attributable, legible, contemporaneous, original, 
Page 52 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
accurate, and complete to ensure accurate interpretation of data.  Clinical site monitoring is conducted 
to ensure that the rights and well-being of human subjects are protected, that the reported trial data 
are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with the 
currently approved protocol, ICH Good Clinical Practice (GCP), and applicable local regulatory 
requirement(s).  During the COVID-19 pandemic, remote monitoring of data may be employed if allowed 
by the local regulatory authority, IRB/IEC, and the study site.
10
DATA QUALITY ASSURANCE
AbbVie will ensure that the clinical trial is conducted with a quality management system that will define 
quality tolerance limits in order to ensure human subject protection and reliability of study results.  Data 
will be generated, documented, and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements.
11
COMPLETION OF THE STUDY
The end-of-study is defined as the date of the last subject's last visit or date of the last follow-up 
contact, whichever is later.
12
REFERENCES
1.
AbbVie. ABBV-951 Investigator's Brochure.
2.
Tomlinson CL, Stowe R, Patel S, et al. Systematic review of levodopa dose equivalency reporting in Parkinson's 
disease. Mov Disord. 2010;25(15):2649-53.
3.
Espay AJ, Pagan FL, Walter BL, et al. Optimizing extended-release carbidopa/levodopa in Parkinson disease: 
Consensus on conversion from standard therapy. Neurol Clin Pract. 2017;7(1):86-93.
Page 53 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX A. STUDY SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
25/100
25 mg/100 mg
AE
adverse event
AESI
adverse event of special interest
aPD
advanced Parkinson's Disease
CD
carbidopa
CD/LD
carbidopa/levodopa
CDP/LDP
carbidopa phosphate/levodopa phosphate
CDP
carbidopa phosphate
CLES
carbidopa-levodopa enteral suspension
COMT
catechol-O-methyltransferase
COVID-19
coronavirus disease - 2019
CSCI
continuous subcutaneous infusion
C-SSRS
Columbia-Suicide Severity Rating Scale
DO
Doctor of Osteopathic Medicine
DTP
direct-to-patient
ECG
electrocardiogram
eCRF
electronic case report form
FAS
Full Analysis Set
FWER
familywise error rate
GCP
Good Clinical Practice
ICD
impulse control disorder
ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use
IEC
independent ethics committee
IFU
instructions for use
IMP
investigational medicinal product
IR
immediate release
IRB
institutional review board
IRT
interactive response technology
Page 54 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
ISE
Infusion Site Evaluation
IUD
intrauterine device
IUS
Intrauterine hormone-releasing system
LCIG
levodopa-carbidopa intestinal gel
LD
levodopa
LDP
levodopa phosphate
MAO
monoamine oxidase
MD
Doctor of Medicine
MDS-UPDRS
Movement Disorder Society-Unified Parkinson's Disease Rating Scale
MedDRA
Medical Dictionary for Regulatory Activities
M-EDL
Motor Aspects of Experiences of Daily Living
MMA
methylmalonic acid
MMRM
mixed model for repeated measures
MMSE
Mini-Mental State Examination
nM-EDL
Non-Motor Aspects of Experiences of Daily Living
NP
Nurse Practitioner
OUS
outside the United States
PA
Physician's Assistant
PCS
potentially clinically significant
PD
Parkinson's disease
PDQ-39
Parkinson's Disease Questionnaire-39 item
PDSS-2
Parkinson's Disease Sleep Scale-2
PhD
Doctor of Philosophy
PKG
Parkinson's KinetiGraph® or Personal KinetiGraph® (United States)
PM-PDSC
Phillips-Medisize - Parkinson's Disease Subcutaneous
PRO
patient-reported outcome
QTc
QT interval corrected for heart rate
QTcF
QTc using Fridericia's correction formula
QUIP-RS
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale
RLS
restless leg syndrome
RSI
reference safety information
SAE
serious adverse event
SAP
statistical analysis plan
Page 55 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
SSR
sample size re-estimation
SUSAR
Suspected Unexpected Serious Adverse Reaction
TA MD
therapeutic area medical director
US
United States
VAS
visual analogue scale
Page 56 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M15-736:  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
Protocol Date: 10 September 2021
Clinical research studies sponsored by AbbVie are subject to the International Council for Harmonisation
of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practices (GCP) and 
local regulations and guidelines governing the study at the site location.  In signing the Investigator 
Agreement, the investigator is agreeing to the following:
1.
Conducting the study in accordance with ICH GCP, the applicable regulatory requirements, 
current protocol and operations manual, and making changes to a protocol only after notifying 
AbbVie and the appropriate Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC), except when necessary to protect the subject from immediate harm.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed consent and 
ethics committees (e.g., IEC or IRB) review and approval of the protocol and its amendments.
4.
Reporting complaints that occur in the course of the investigation(s) to AbbVie.
5.
Reading the information in the Investigator's Brochure/safety material provided, including the 
instructions for use and the potential risks and side effects of the investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the study about 
their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making those records 
available for inspection by representatives of AbbVie and/or the appropriate regulatory agency, 
and retaining all study-related documents until notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and approved the initial 
clinical protocol and all of its amendments.
9.
Reporting promptly, all changes in the research activity and all unanticipated problems involving 
risks to human subjects or others, to the appropriate individuals (e.g., coordinating investigator, 
institution director) and/or directly to the ethics committees and AbbVie.
10. Providing direct access to source data documents for study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s).
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)
Page 57 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX C. LIST OF PROTOCOL SIGNATORIES
Name
Title
Functional Area
Neuroscience Development
Neuroscience Development
Data and Statistical Sciences
Neuroscience Development
Clinical Program Development
Medical Writing
Page 58 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX D. ACTIVITY SCHEDULE
Required study activities are shown in the following table.  Individual activities are described in detail in 
Section 3 of the Operations Manual (Appendix F).  Allowed modifications due to COVID-19 are detailed 
within the Operations Manual.  Subjects who prematurely discontinue before the Randomization Visit 
(V6) do not need to complete V13 assessments; a follow-up visit or phone call will be completed 30 days 
after the last dose of study drug, if the subject is willing, to ensure all treatment-emergent AEs/SAEs 
have been resolved.  If a subject prematurely discontinues blinded study drug, V13 assessments (also 
the Premature Discontinuation Visit for the Double-Blind Treatment Period) should be completed as 
soon as possible, preferably within 2 weeks.
Page 59 of 115


















STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX E. PROTOCOL SUMMARY OF CHANGES
Previous Protocol Versions
Protocol
Date
Version 1.0
22 October 2019
Version 2.0
23 January 2020
Version 3.0
26 March 2020
Version 4.0
04 September 2020
The purpose of this version is to make minor clerical edits and corrections for clarity and consistency 
throughout the protocol, as well as to change the list and ranking of secondary endpoints included in 
Type I error control prior to database lock and unblinding of Study M15-736.  The changes to secondary 
endpoints are based on results from an interim analysis of open-label Phase 3 Study M15-741 as follows: 

Moved presence of morning akinesia at Week 12 from other secondary endpoints to key 
secondary endpoints.

Added change from Baseline to Week 12 in hours of average daily normalized "On" time without 
dyskinesia to the list of other secondary endpoints.

Moved PDSS-2 total score up in the list of other secondary endpoints so that it is ranked before 
the PDQ-39 summary index and EQ-5D-5L summary index.
Page 68 of 115


STUDY M15-736  |  Version 5.0  |  EudraCT 2019-003930-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX F. OPERATIONS MANUAL
Page 69 of 115




p. 2 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 CONTACTS
Sponsor/
Emergency 
Medical Contact
Sponsor Contact:
AbbVie Inc.
1 North Waukegan Road 
North Chicago, IL 60064
Emergency Medical Contact:
AbbVie Inc.
1 North Waukegan Road
North Chicago, IL 60064
Office:
Mobile:
Fax:
Email:
Office:
Mobile:
Fax:
Email:
EMERGENCY 24-hour Number:  
+1 973-784-6402
Safety Concerns
Neuroscience Safety Team
AbbVie Inc.
1 North Waukegan Road
North Chicago, IL 60064
Phone:
+1 847-938-4191
Email:  
SafetyManagement_Neuroscience@abbvie.com
SAE Reporting 
outside of RAVE
Clinical Pharmacovigilance
Fax:
+1 847-938-0660
Email:
PPDINDPharmacovigilance@abbvie.com
Protocol 
Deviations
AbbVie Inc
1 North Waukegan Road
North Chicago, IL 60064
Phone:
Email:
Certified Clinical 
Lab
Labcorp Central Laboratory Services SA
8211 Scicor Drive
Indianapolis, IN 46214
Phone:
+1 866-762-6209 (toll free)
+1 317-271-1200 (local calls)
Fax:
+1 317-616-2361
Page 71 of 115


p. 3 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
TABLE OF CONTENTS
1
CONTACTS
2
2
PROTOCOL ACTIVITIES BY VISIT
5
2.1
SCREENING PERIOD ACTIVITIES
6
2.2
ORAL CD/LD STABILIZATION PERIOD ACTIVITIES
8
2.3
DOUBLE-BLIND TREATMENT PERIOD ACTIVITIES
10
2.4
POST-TREATMENT ACTIVITIES
18
3
STUDY PROCEDURES
19
3.1
STUDY SUBJECT INFORMATION AND INFORMED CONSENT
19
3.2
ELIGIBILITY CRITERIA
19
3.3
PM-PDSC PUMP DELIVERY SYSTEM TRAINING (SCREENING THROUGH ENROLLMENT)
20
3.4
MEDICAL/SURGICAL HISTORY
20
3.5
CLINICAL ASSESSMENTS
20
3.6
ADVERSE EVENT ASSESSMENT
21
3.7
INFUSION SITE EVALUATION
21
3.8
PRIOR AND CONCOMITANT MEDICATIONS
22
3.9
PATIENT-REPORTED OUTCOMES
22
3.10 HEIGHT AND WEIGHT
30
3.11 VITAL SIGNS
30
3.12 PHYSICAL EXAMINATION
31
3.13 NEUROLOGICAL EXAMINATION
31
3.14 12-LEAD ELECTROCARDIOGRAM
31
3.15 CLINICAL LABORATORY TESTS
32
3.16 DRUG SCREEN
35
3.17 STUDY DRUG PRESCRIPTION RECORD
36
3.18 PM-PDSC PUMP DELIVERY SYSTEM TRAINING
36
3.19 STUDY DRUG AND PM-PDSC PUMP DELIVERY SYSTEM DISPENSATION AND RETURN
37
3.20 SUBJECT WITHDRAWAL FROM STUDY
37
3.21 HOME HEALTHCARE SERVICE DUE TO COVID-19 PANDEMIC
38
Page 72 of 115


p. 4 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
4
SAFETY MANUAL
38
4.1
METHODS AND TIMING OF SAFETY ASSESSMENT
38
4.2
REPORTING ADVERSE EVENTS AND INTERCURRENT ILLNESSES
39
4.3
PRODUCT COMPLAINT REPORTING
41
5
COUNTRY-SPECIFIC REQUIREMENTS
41
5.1
SUSAR REPORTING
41
5.2
TREATMENT AFTER END OF STUDY
41
6
REFERENCES
41
7
APPENDICES
42
7.1
NEUROLOGY LABORATORY GRADING
42
7.2
CRITERIA FOR POTENTIALLY CLINICALLY SIGNIFICANT VITAL SIGN AND WEIGHT VALUES
46
Page 73 of 115


p. 5 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
2 PROTOCOL ACTIVITIES BY VISIT
Study visits may be impacted due to the COVID-19 pandemic.  This may include changes such as phone 
or virtual visits, visits at alternative locations, or changes in the visit frequency and timing of study 
procedures, among others.  Additional details are provided in the subsequent section.  Every effort 
should be made to ensure the safety of subjects and site staff, while maintaining the integrity of the 
study.  If visits cannot be conducted onsite due to travel restrictions or other pandemic-related reasons, 
follow the updates below on how to proceed.
If a subject has screened, and is unable to complete screening activities on site after Screening Visit 1, it 
is preferable to extend the Screening Period as described below in Section 2.1 rather than perform 
remote Visits 3 and 4 (optional), because Visit 5 must be performed on site.  The guidance that is 
provided for Visit 3 and beyond should be followed if the COVID-19 restrictions at your site have 
changed once your subject is enrolled, or after they have been randomized.
This guidance leverages the home health nurses (HHN) that are provided for the study.  Sites unable to 
use this service due to institutional or IRB policy, or another reason approved by AbbVie should contact 
their primary site monitor.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
During the COVID-19 pandemic, if it is not possible for all study procedures to be performed as specified 
due to travel restrictions or other reasons, the following modifications are allowed:

If permitted by local regulations, the IRB/IEC and the subject, Visits 2, 3, 4, and 7, 8, 9, 10, 11, 
and 12 may be conducted in the subject's home residence.

Some study visits and/or activities may be performed by phone/virtually.  These are indicated by 
a hashtag (#) in the appropriate visit tables below.

Some study visits and/or activities may be performed in person at the subject's home by an
HHN, the site staff or direct-to-patient delivery, depending on the activity.  These are indicated 
by an asterisk (*) in the appropriate visit tables below.

Some study visits and/or activities may be performed by phone/virtually in conjunction with a 
person at the subject's home: health nurse, the site staff or direct-to-patient delivery, 
depending on the activity.  These are indicated by an asterisk and hashtag (*#) in the 
appropriate visit tables below. 

During a virtual visit, activities that do not need to be performed are indicated by a minus 
sign (–).

Scheduled and unscheduled labs may be drawn by a local clinic/hospital/laboratory if COVD-19 
restrictions prevent a subject to visit the site.  All procedures performed at local facilities must 
be performed by appropriately qualified personnel.

Study visits and/or activities should be performed as scheduled whenever possible.  If it is not 
possible to do so due to the pandemic, the following modifications are allowed:

For Visit 5, Visit 6, and Visit 13, if the visit cannot be rescheduled within the visit window, 
contact the sponsor. Subjects should remain on the prescribed oral CD/LD IR regimen and 
Page 74 of 115


p. 6 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
concomitant PD medication until starting blinded study drug at V6, and remain on the 
double-blind study drug as much as possible through D85/Premature Discontinuation Visit 
(V13) even if a visit is not occurring on the designated study day.
If an activity is missed during a virtual visit, perform the activity at the earliest feasible opportunity.  
Laboratory draws must be obtained as soon as feasible.
2.1 Screening Period Activities
This section presents a list of activities performed at Screening Visit 1 (V1) and Screening Visit 2 (V2).  
Activities are grouped by category (Interview, Exam, etc.).  Details about each activity are provided in 
Section 3.
Page 75 of 115


























p. 19 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
3 STUDY PROCEDURES
3.1 Study Subject Information and Informed Consent
The investigator or his/her representative will explain the nature of the study to the subject (and 
caregiver, if applicable) and answer all questions regarding this study.  Prior to any study-related 
screening procedures being performed on the subject or any medications being discontinued by the 
subject in order to participate in this study, the informed consent statement(s) will be reviewed, signed, 
and dated by the subject, the person who administered the informed consent, and any other signatories 
according to local requirements.  A copy of the signed informed consent will be given to the subject and 
the original will be placed in the subject's medical record.  An entry must also be made in the subject's 
dated source documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy.  If a caregiver will be trained on the PM-PDSC 
Pump and/or will be participating in the Exit Interview, the caregiver will also be required to provide 
consent.
Information regarding benefits for subjects and information regarding provisions for treating and/or 
compensating participants who are harmed as a consequence of participation in the study can be found 
in the informed consent form.
Due to the COVID-19 pandemic, it is possible that additional protocol modifications not outlined in this 
protocol may become necessary.  If this situation arises, in addition to the study informed consent, 
additional verbal consent may be obtained prior to these adaptations or substantial changes in study 
conduct in accordance with local regulations.
Informed consent will be obtained at Screening Visit 1 (V1) as shown in Section 2.1.
3.2 Eligibility Criteria
All subjects will be evaluated to ensure they meet the eligibility criteria during the Screening Period.  
Subjects must meet all eligibility criteria prior to the Oral CD/LD Stabilization Period and the 
administration of open-label oral study drug at V3.  Subjects must continue to meet these eligibility 
criteria prior to randomization (V6) and administration of double-blind study drug.
Note: At V2 and prior to a subject's enrollment (V3), the investigator or designee must confirm eligibility 
criteria in EDC.  The TA MD or designee [contact information on cover page] are readily available to 
discuss any questions the Investigator or designee may have regarding appropriateness of study 
participation for a specific subject or the eligibility criteria.  The decision to enroll the subject is 
ultimately the investigator's responsibility.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
If the Screening Period cannot be completed within 60 days due to an extenuating event (e.g., genuine 
emergency, natural disaster), contact the TAMD for a case-by-case review and approval of potential 
rescreens (e.g., due to COVID-19-related disruptions) that prevent screening within 60 days.
Page 88 of 115


p. 20 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Rescreened subjects will need to repeat all screening visits and screening procedures (except for the 
concordance testing) and demonstrate that they still qualify prior to enrollment (V3).
3.3 PM-PDSC Pump Delivery System Training (Screening Through 
Enrollment)
Leading up to V2, subjects (and caregivers, if applicable) will continue to be trained on the correct use of 
the PM-PDSC Pump Delivery System at the study site or the subject's home.  At V2, the subject (or 
caregiver) must demonstrate the understanding and correct use of the delivery system, including the 
insertion of the cannula into the subject's abdomen, as assessed by the investigator or designee using 
the PM-PDSC Knowledge and Skills Checklist. Subjects who fail this requirement may repeat it once (at 
an unscheduled visit prior to V3) but must be screen failed if the criterion is still not met.  Additionally, 
during the Screening Period, subjects may become familiar with and simulate the experience of wearing 
a delivery system via a mock infusion delivery system where available. The mock system will 
approximate the dimensions, weight, tubing and other general physical features of the PM-PDSC 
Delivery System, but it will not be functional and subjects will not insert a cannula in their abdomen nor 
infuse any solution.
Subjects (and caregivers, if applicable) will continue to be trained on the correct use of the PM-PDSC 
Pump Delivery System leading up to V5 and must again demonstrate at V5 the understanding and 
correct use of the delivery system, including the insertion of the cannula into the subject's abdomen, as 
assessed by the investigator or designee using the PM-PDSC Knowledge and Skills Checklist. Subjects 
who fail this requirement must be prematurely discontinued.  V5 will be the Baseline Visit, unless 
otherwise indicated.
3.4 Medical/Surgical History
A complete medical and surgical history, including demographics, nicotine use, and histories of alcohol 
or drug abuse, that in the investigator's judgment might impact compliance with study execution, will be 
taken at the Screening Visit 1 (V1), as shown in Section 2.1.  Additionally, chronic disorders 
(e.g., diabetes, hypertension, hay fever, polyneuropathy) diagnosed prior to V1 and still present at V1 
should be recorded on the Medical History Form.  The medical history obtained at V1 will serve as the 
Baseline for clinical assessment.  All psychiatric, neurological, and/or cognitive diagnoses should be 
reported.  Updates should be made to the medical/neurological/PD history with any findings from 
laboratories, dermatologists, etc. related to the period before initiation of blinded study drug.  
Medication (prescription or over-the-counter, including vitamins and herbal supplements) use from 
30 days prior to informed consent form signature through the end of the study will also be recorded.
3.5 Clinical Assessments
A clinical assessment will be conducted on all subjects at V1, as shown in Section 2.1.  This will include 
an assessment of the subject's PD treatment history.  To qualify for enrollment in the study, the subject 
should provide the investigator with a comprehensive history of their current and past (possibly up to 
5 years) PD medication.  This should be done according to the subject's and/or caregiver's (if applicable)
recollection, as well as available history in a subject's chart.
Page 89 of 115


p. 21 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
3.6 Adverse Event Assessment
Adverse events will be assessed at every visit throughout the study as shown in Section 2.  The 
investigator will routinely monitor each subject for clinical and laboratory evidence of AEs throughout 
the study.  The investigator will assess and record any AE in detail including the date of onset, event 
diagnosis (if known) or sign/symptom, severity, time course (end date, ongoing, intermittent), 
relationship of the AE to study drug, and any action(s) taken.
For SAEs considered as having no reasonable possibility of being associated with study drug or the study 
device components, the investigator will provide an "other" cause of the event.  For AEs to be 
considered intermittent, the events must be of similar nature and severity.  Adverse events, whether in 
response to a query, observed by clinical study personnel, or reported spontaneously by the subject will 
be recorded.
All AEs will be followed to a satisfactory conclusion.
See also Section 4.2.
3.7 Infusion Site Evaluation
The investigator or qualified designee will evaluate the infusion site area (abdomen) from Day 2 (V7)
through the end of the study, at each study visit, as shown in Section 2.3.  A 2-part (numeric and letter 
grading) evaluation scale will be used to assess irritation:1
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
Any observation of infusion site reaction with irritation criteria > 2 or > C must be recorded as an 
adverse event (AE).
Page 90 of 115


p. 22 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Dermatologic Assessments
If any moderate to severe infusion site-related AE, such as cellulitis/abscess formation, ecchymoses, 
subcutaneous nodules, or scarring occurs, or if any infusion site-related reaction is assessed with an 
irritation numeric grade equal to 7 on the Infusion Site Evaluation scale, the investigator or designee is 
instructed to do the following, which will be documented in the eCRF:
1.
Photograph the skin reaction and follow the appropriate procedure for submission of the 
photographs.  In rare situations where an assessment or visit cannot be completed onsite due to 
an extenuating event (e.g., genuine emergency, natural disaster, COVID-19-related conditions),
the subject may be asked to obtain and submit a self-captured photograph of the skin reaction.
2.
Refer the subject to a dermatologist for comprehensive evaluation (including skin biopsy, if 
applicable), treatment, and follow-up per standard practice.  The subject should be referred to a 
dermatologist within 2 business days after the photographs are taken.  The dermatologic visit 
should be completed within 2 weeks after identification of the AE or skin reaction that meets 
the above criteria.  While an in-person dermatology evaluation is preferred, this assessment 
may be performed as a telemedicine visit per the dermatologist's standard practice.
Photography data will be considered source documentation. Dermatologic assessments may be
performed during clinic visits (scheduled or unscheduled).
Sites will request medical records from the dermatologic visit. Upon receipt of records or reports 
generated from the dermatologic visit, sites will promptly submit them to AbbVie or designee consistent
with typical study data reporting requirements.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
Due to the COVID-19 pandemic, subject visits may be conducted via phone or video conference.  The 
Infusion Site Evaluation (ISE) is eligible for completion by interview at V7, V8, V9, V10, V11, and V12.  In 
this situation, the ISE: may be completed via video if the picture is of sufficient quality; report AEs per 
protocol, request subject/caregiver to describe the reaction (redness, swelling, etc.); if ISE meets criteria 
for dermatologic assessment, request that a photo of the reaction be provided to the site.
3.8 Prior and Concomitant Medications
Investigators and/or trained site staff will review and record all prior and concomitant medications at 
every visit throughout the study as shown in Section 2.
3.9 Patient-Reported Outcomes
Patient-reported outcomes (PRO) instruments include the following:

Self-Administered PRO Instruments:  Subjects will complete the PD Diary Concordance, Subject 
Dosing Diary, PD Diary, and EQ-5D-5L.  Subjects should be instructed to follow the instructions 
provided with the PRO instrument and to provide the best possible response to each item.  
Clinical study personnel shall not provide interpretation or assistance to subjects other than 
Page 91 of 115


p. 23 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
encouragement to complete the tasks.  Clinical study personnel will encourage completion of 
the PRO instrument at all specified visits and will make every effort to ensure that a response is 
entered for all items.  Subjects will also wear the PKG watch (based on local country 
regulations).

Rater-Administered PRO Instruments:  Subjects will complete the following rater-administered 
instruments: Mini-Mental State Examination (MMSE), Movement Disorder Society-Unified 
Parkinson's Disease Rating Scale (MDS-UPDRS), Columbia-Suicide Severity Rating Scale (C-SSRS), 
and Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale 
(QUIP-RS).

Central Rater Required:  The Parkinson's Disease Sleep Scale-2 (PDSS-2) and Parkinson's 
Disease Questionnaire-39 item (PDQ-39) will be administered by a qualified blinded central 
rater.
All applicable clinical, safety, and health-outcome assessments will be administered only by 
individuals qualified by the sponsor.
Note:  Every effort must be made by the investigative sites to ensure that each subject is rated 
by the same rater throughout the subject's participation in the study to minimize sources of 
variability.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
Due to the COVID-19 pandemic, subject visits may be conducted via phone or video conference.  PROs 
eligible for completion by interview at such visits are V2, V3, V4, and V7, V8, V9, V10, V11, and V12.  In 
this situation, sites will read the PRO questions and response options to the subject and record the 
subject's responses.  The subject's ability to view the PRO to understand the questions and response 
options should be preserved.  Sites may share the questionnaire by videoconference or send the 
questionnaires (email or hard copy) to the subjects to allow them to read/understand the questions and 
responses when the subject is providing responses over the phone.  The date and time of PRO data 
collection should be recorded along with who collected the information.

SLATE Device PRO (i.e., rater tablet): Preferred method is to collect data using direct entry into 
the SLATE device, even when collected remotely.  Paper PROs can be utilized as a backup plan.  
Specifications are outlined below.

Site Rater administered scales: This includes C-SSRS, MDS-UPDRS, and QUIP-RS, as applicable 
for each visit. The qualified rater at your site will conduct those assessments remotely except 
for the MDS-UPDRS Part III (Motor Examination). As default, the system does not allow raters to 
jump to the MDS-UPDRS Part IV without having completed Part III which, in this case, should be 
completed with all zeros (0's) before launching a data clarification form in TrialMax to get this 
documented.

Paper PROs can be used as a backup plan.

The PRO scales or screenshots have been provided to IRB/EC according to local 
regulations, and your site should use the version provided to the IRB/EC for paper 
collection in your local language.  If your site is not able to pull up IRB/EC portal to obtain 
scale, contact your primary monitor for assistance.
Page 92 of 115


p. 24 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Your source documentation should clearly indicate how each scale was obtained (e.g., in-
person, phone, video) with time/date noted for each scale.  More information will be 
forthcoming on how to transfer paper documentation to SLATE device and/or EDC.
The PRO assessments are described below after the Rater Training Requirements.
Rater Training Requirements
Prior to administration of respective scale(s), designated site and central raters will be trained on and 
certified (if appropriate) in the use of the scales they will administer in this study.  The objective of this 
certification/training is to ensure uniformity within and across raters and across sites in the 
administration and scoring of these assessments, thereby reducing variability.
The sponsor, in conjunction with the selected rater training vendor, will determine the minimum rater 
qualifications for each of the rating scales.  All raters must meet these qualifications prior to 
participation in the training process.  The names and qualifications of all clinical study personnel to be 
involved in rating scale administration will be submitted for approval upon site selection.
The qualifications of the raters will be verified through the training vendor.  Qualified raters will be 
trained and tested and, if they meet established requirements, certified accordingly.  Individual 
exceptions to these requirements may only be approved by the sponsor via the rater training vendor.
Only those persons who have been trained as raters for this study may rate subjects.  Raters who cannot 
participate in the initial pre-study training or who become involved in the study at a later time will not 
be permitted to perform study ratings until they have satisfactorily completed an individualized training 
program designed by the rater training vendor if applicable, approved by AbbVie, and supervised by the 
investigator or his/her designee.  Raters may be reassessed periodically throughout the study.
The efficacy raters will not have access to the results of other study assessments or medical records for 
the subject, will not participate in the care, or management of the subject, in order to maintain the 
study blinding.  Therefore, study sites will identify and submit appropriate personnel for rater 
qualification and training, taking into account their site roles and the blinding considerations described 
in Protocol Section 5.8.
Subject Dosing Diary
Subjects will complete a dosing diary.  The time a new syringe is started (with or without a loading dose), 
stoppage in therapy (e.g., vial change-out, shower), pump alarms (e.g., occlusion alarm), blinded oral 
study drug times and doses, and CD/LD IR tablets self-administered by the subject during the study as 
possible rescue therapy should be recorded for 3 consecutive days prior to any study visits (as specified 
in Section 2).  Additionally, all instances during the Treatment Period of the administration of oral CD/LD 
IR tablets as rescue therapy should be documented in the dosing diary (i.e., not only the 3 days prior to 
study visits).  Rescue therapy can be administered in half or whole tablets of CD/LD IR, as needed 
(e.g., ½ tablet, 1 tablet, 1 ½ tablet, 2 tablets).  Completed dosing diaries should be reviewed by the 
investigators at every study visit.  Half tablets are not allowed in the case of pump malfunction when the 
blinded study drug infusion and blinded study drug capsules should be stopped.
Page 93 of 115


p. 25 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Note:  Subjects should be reminded with a phone call at least 4 days prior to each visit to complete the 
dosing diary and to reinforce the importance of dosing diary completion.  If during the study, the subject 
incorrectly completes the dosing diary, they should receive re-training on dosing diary completion.
Parkinson's Disease Diary
PD Diary Subject Training and Requirements
The subject will be required to have PD Diary training that will include how to understand their PD 
symptomatology and how to complete the PD Diary.  Training will occur during V1.
PD Diary Concordance Assessment
Following the initial PD Diary training during V1, the subject will complete a PD Diary on the touch 
(handheld) device over a minimum of 3 hours for a concordance evaluation while he/she is in the clinic 
at V1 as shown in Section 2.1.  During this period, the subject must experience at least 1 transition from 
"Off" to "On" or from "On" to "Off," which must be observed by the investigator or a qualified rater.  
The investigator or an experienced and medically qualified study site designee (e.g., NP, PA, DO, MD, or 
PhD) assigned by the investigator will also complete a separate PD Diary on the Slate (tablet) device for 
this period indicating their assessment of the subject's motor state.  There must be at least 75% 
concordance between the subject's PD Diary and the PD Diary completed by the investigator or qualified 
designee.  If no transition from "Off" to "On" or from "On" to "Off" occurs during the time of 
concordance evaluation and/or the concordance is lower than 75%, the concordance testing may be 
prolonged at the investigator or designee's discretion.  If the concordance is less than 75%, the subject 
will undergo re-training of PD Diary completion and may repeat the concordance evaluation one more 
time before completing the PD Diary at home.
Completion of the PD Diary
The core of the PD Diary is the questionnaire that the subject will use to record Parkinsonian symptoms.  
The subject will be prompted to record in the PD Diary whether he/she has been "On," "Off," or 
"Asleep" and what the severity of his/her dyskinesia (troublesome or not troublesome) was.  The PD 
Diary is to be completed for a full 24-hour period of each day, reflecting both time awake and time 
asleep.  On PD Diary recording days, the subject will be instructed to make an entry upon waking and 
every 30 minutes during their normal waking time and upon awakening from time asleep.
The PD Diary will be completed on 3 consecutive days prior to V2, and prior to each study visit specified 
in Section 2.  Subjects who do not meet the required minimum 2.5 hours of "Off" time on average (with 
a minimum of 2 hours of "Off" time per day) across the 3 consecutive days prior to V2, may repeat the 
PD Diary for 3 additional consecutive days during the Screening Period.  If the criterion is still not met 
after this, subjects must screen fail.
The PD Diary will also be completed for 3 consecutive days (which should be started at least 4 days prior 
to V6, i.e., PD Diaries need to be completed prior to Day –1) to confirm eligibility before randomization.  
Subjects who do not meet the required minimum of at least 2 hours of "Off" time each day for 
3 consecutive days before V6 (Randomization) must be prematurely discontinued from the study.
Note:  Subjects should be reminded with a phone call at least 4 days prior to each visit (at least 5 days 
prior to V6) to complete the PD Diary and to reinforce the importance of PD Diary completion.  A 
Page 94 of 115


p. 26 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
minimum of 44 out of 48 entries are required for each 24-hour period for a valid entry. If during the 
study, the subject incorrectly completes the PD Diary, they should receive re-training on PD Diary
completion.
EQ-5D-5L
The EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of 
health-related quality of life that can be used in a wide range of health conditions and treatments.  The 
EQ-5D-5L consists of 2 parts:  the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).
The descriptive system comprises 5 dimensions:  mobility, self-care, usual activities, pain/discomfort, 
and anxiety/depression.  Impairment in each of the 5 dimensions is measured on a 5-level scale, where 
1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, and 5 = extreme 
problems.  The patient is asked to rate his/her current health by ticking the box next to the statement 
that most appropriately describes their health status in each of the 5 dimensions.  The patient's overall 
health can be described as a single number (formed by the combination of the levels of impairment 
across each of the 5 dimensions) that ranges from 11111 (full health/no problems) to 55555 (extreme 
impairment in all dimensions).  The health status is converted to an index value using the country-
specific weighted scoring algorithm for the United States (US).  The index value for the US ranges from a 
worst score of –0.109 to a best score of 1.
In addition, the patient is also asked to self-rate their current health on a vertical visual analogue scale 
(VAS).  The scale ranges from 0 (labelled as "the worst health you can imagine") to 100 (labelled as "the 
best health you can imagine").  The VAS provides a complementary approach to the descriptive system 
for quantifying the patient's health based on their own judgment.
Subjects will complete the EQ-5D-5L at the study visits specified in Section 2.
Parkinson's KinetiGraph
Developed by Global Kinetics Corporation, the Parkinson's KinetiGraph® system (PKG or Personal 
KinetiGraph® as it is known in the US), is an innovative mobile health technology.  The PKG provides 
continuous, objective, ambulatory assessment of the symptoms of PD including tremor, bradykinesia, 
and dyskinesia.  The PKG also provides an assessment of daytime somnolence.  The PKG system consists 
of a wrist-worn movement recording device known as the PKG Watch, proprietary algorithms, and a 
data-driven report known as the PKG.  Data are collected continuously by the PKG Watch during 
activities of daily living in the home environment.  The PKG Watch should be worn by the subject 
continuously except for recharging once a week (e.g., the night of the 7th day every week).  The data are 
uploaded to a proprietary cloud system for processing at the time of recharging.
Subjects will be required to wear the PKG watch (reference the currently approved manufacturer's 
directions) from V1 to Day 85 (V13) in the countries where allowed.  In the US only, the PKG watch is 
approved by the US Food and Drug Administration for use by PD subjects from 46 – 83 years of age.  The 
AbbVie TA MD should be consulted if, in the investigator's opinion, there are circumstances that might 
interfere with the use of the PKG device (e.g., religious reasons, atopic dermatitis).
During the Screening Period (i.e., 6 - 8 days before V3), subjects should be active (engaged in usual 
activities of daily living and not sitting or resting on a couch or chair or lying in bed) for at least 
30 minutes before taking their habitual first dose of oral PD medications.
Page 95 of 115


p. 27 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Mini-Mental State Examination
The MMSE is a brief 30-point questionnaire administered by a qualified rater, that provides a 
quantitative measure of cognitive status in adults and is used widely to screen for cognitive impairment 
and to estimate the severity of cognitive impairment at a given point in time, to follow the course of 
cognitive changes in a patient over time, and to document response to treatment.
The MMSE will be used in this study to screen for cognitive impairment.  The MMSE score ranges from 
0 to 30 with lower scores indicating greater impairment.  The subject must have a total score ≥ 24 at V1 
to be eligible for study participation.  A qualified rater will administer the MMSE.
Movement Disorder Society-Unified Parkinson's Disease Rating Scale
The MDS-UPDRS is an investigator-used rating tool to follow the longitudinal course of PD.  Study sites 
should make every effort to ensure that each subject is rated by the same rater throughout the subject's 
participation in the study.  The MDS-UPDRS assessment will be performed by a qualified rater.  To be 
qualified by the sponsor and the rater vendor, all raters must have participated in the rater training and 
have a current valid rater certificate.
The MDS-UPDRS consists of the following sections:
Part I:
Non-Motor Aspects of Experiences of Daily Living (nM-EDL)
Part II:
Motor Aspects of Experiences of Daily Living (M-EDL)
Part III:
Motor Examination (including Hoehn and Yahr stage)
Part IV:
Motor Complications
Some sections require that multiple grades be assigned to each extremity.  The MDS-UPDRS total score 
(Parts I - III) ranges from 0 to 236 with 236 representing the worst (total) disability, and 0 representing 
no disability.
At all indicated visits specified in Section 2, a complete MDS-UPDRS (Parts I - IV) should be administered 
in the subject's best "On" time and, if possible, at the same time of day at each visit throughout the 
study.
Columbia-Suicide Severity Rating Scale
The C-SSRS is a systematically administered instrument designed to assess suicidal behavior and 
ideation, track and assess all suicidal events, and assess the lethality of attempts.  Additional features 
assessed include frequency, duration, controllability, reason for ideation, and deterrents.
Any subject who has suicidal ideation with plan within the last year, either via answering "yes" to 
Question 4 and/or Question 5 to the suicidal ideation portion of the C-SSRS, or via clinical interview, will 
be evaluated immediately by the investigator.  The AbbVie TA MD must also be notified.  In addition, if 
the subject expresses suicidal ideation at any time during the study, the investigator and the AbbVie TA 
MD should be notified immediately.
Page 96 of 115


p. 28 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Under no circumstances should a subject who has positively endorsed or expressed suicidal ideation be 
left alone, be allowed to exit the site, or go home before a qualified medical professional has evaluated 
the subject's risk.
A qualified rater will administer the C-SSRS at the visits as shown in Section 2.  The Baseline/Screen 
version will be administered at V1, while the Since Last Visit version will be administered at all 
subsequent visits.
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale
The QUIP-RS is a brief, self-completed or rater-administered rating scale to assess the severity of 
symptoms of impulse control disorders (ICDs) and related behaviors reported to occur in PD.  In this 
study, QUIP-RS will be rater-administered.  The QUIP-RS can also aid in supporting a diagnosis of ICDs 
and related disorders in PD.  The QUIP-RS uses a 5-point Likert scale that requires individuals to rate the 
severity of each symptom based on its frequency.  The potential advantages to using a rating scale 
include detection of subsyndromal behaviors, establishment of clear cutoff points with a good balance 
between sensitivity and specificity, and the ability to monitor changes in symptoms over time.
The QUIP-RS has 4 primary questions (pertaining to commonly reported thoughts, urges/desires, and 
behaviors associated with ICDs), each applied to the 4 ICDs (compulsive gambling, buying, eating, and 
sexual behavior) and 3 related disorders (medication use, punding, and hobbyism).  It uses a 5-point 
Likert scale (score 0 – 4 for each question) to gauge the frequency of behaviors and instructs patients to 
answer questions based on behaviors that occurred in the preceding 4 weeks (or any 4-week period in a 
designated time frame).  The QUIP-RS is administered with an instruction sheet that provides examples 
of the behaviors being assessed and a brief description of the Likert scale categories for frequency 
(i.e., never [0] = not at all, rarely [1] = infrequently or 1 day/week, etc.).  Scores for each ICD and related 
disorder range from 0 to 16, with a higher score indicating greater severity (i.e., frequency) of 
symptoms.  Due to overlap, hobbyism and punding were combined in the validation process to form a 
single diagnosis (hobbyism-punding), with a total score ranging from 0 to 32 for the combined disorder.  
The total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112.
The behaviors can be described as:
(i)
Gambling (casinos, internet gambling, lotteries, scratch tickets, betting, or slot or poker 
machines);
(ii)
Sex (making sexual demands on others, promiscuity, prostitution, change in sexual 
orientation, masturbation, internet or telephone sexual activities, or pornography);
(iii)
Buying (too much of the same thing or things that you don't need or use);
(iv)
Eating (eating larger amounts or different types of food than in the past, more rapidly 
than normal, until feeling uncomfortably full, or when not hungry);
(v)
Hobbyism (specific tasks, hobbies or other organized activities, such as writing, painting, 
gardening, repairing or dismantling things, collecting, computer use, working on 
projects, etc.);
(vi)
Punding (repeating certain simple motor activities, such as cleaning, tidying, handling, 
examining, sorting, ordering, collecting, hoarding, or arranging objects, etc.);
Page 97 of 115


p. 29 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
(vii)
Medication use (consistently taking too much of your Parkinson's medications, or 
increasing on your own, without medical advice, your overall intake of Parkinson's 
medications)
The frequency of behaviors is described as never (0) = not at all, rarely; (1) = infrequently or 1 day/week; 
sometimes (2) = at times or 2 to 3 days/week; often (3) = most of the time or 4 – 5 days/week; very 
often (4) = nearly always or 6 - 7 days/week.
A qualified rater will administer the QUIP-RS at the times described in Section 2.
Parkinson's Disease Sleep Scale-2
Although several scales exist to evaluate sleep disturbances, only 3 are endorsed and recommended by 
the Movement Disorders Society.  One such scale is the PD Sleep Scale (PDSS), which has been modified 
to PDSS-2).  The purpose of the PDSS-2 is to characterize the various aspects of nocturnal sleep 
problems in patients with PD.  The PDSS-2 instrument has been shown to be reliable, valid, precise, and 
a potentially treatment-responsive tool for measuring nocturnal disabilities and sleep disorders in PD.  
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), PD 
symptoms at night (5 items), and disturbed sleep (5 items).  Specifically, the questions assess overall 
sleep quality, insomnia, sleep fragmentation, restless leg syndrome (RLS) and periodic leg movements of 
sleep, rapid eye movement behavior disorder, hallucinations, nocturia, nocturnal immobility, pain and 
cramps, morning akinesia, tremor, and sleep apnea.  The PDSS-2 was developed from the PDSS based 
upon the need for a treatment measuring tool containing PD-specific sleep disorders; the instrument 
was extended to address specific sleep disturbances such as RLS, akinesia, pain, and sleep apnea.  
Daytime sleepiness was removed from the PDSS-2, as it is a more complex PD symptom.
To increase ease of use, the visual analogue scale of the PDSS was transformed into a frequency 
measure in the PDSS-2.  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 domain as well as a total score.  The 
recall period is for the past week.
The PDSS-2 will be administered via telephonic interview by a qualified blinded central rater at the visits 
specified in Section 2.
Parkinson's Disease Questionnaire-39 item
The PDQ-39 is a disease-specific instrument designed to measure aspects of health that are relevant to 
subjects with 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 are presented as 8 discrete domain scores and as a summary index.  The 
PDQ-39 domain scores and summary index range from 0 to 100, where lower scores indicate a better 
perceived health status.
Page 98 of 115


p. 30 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
The PDQ-39 will be administered via telephonic interview by a qualified blinded central rater at the visits 
specified in Section 2.
Infusion Site Rotation Tool
To help guide their infusion site rotation pattern and help prevent overuse of an infusion site area,
subjects will use an Infusion Site Rotation Tool. Subjects will track each infusion site by recording the 
date corresponding to the abdomen location used. Site personnel will train subjects on this tool on or 
prior to Day 1.  Subjects should receive re-training on using the tool as needed (e.g., if they are not 
correctly recording or forgetting to record infusion sites used).
Exit Interview
Subjects (and caregivers, if applicable) will be asked to provide answers to brief questions about their 
study participation and experience, including their estimate of whether they were assigned to ABBV-951 
solution or placebo solution and the reason for their choice. Study sites should ensure that subjects and 
caregivers independently provide the responses and that this interview is the last activity of the last 
study visit to minimize bias. The site will record the responses into EDC.
3.10 Height and Weight
Height will be measured at V1 only; weight will be measured at the visits specified in Section 2.  The 
subject should not wear shoes during either measurement.
See Section 7.2 for criteria for PCS weight values.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
Due to the COVID-19 pandemic, subject visits may be conducted via phone or video conference.  In
these situations, height and weight measurements may be performed by the subject or caregiver as 
needed and recorded in the source. These data should not be recorded in EDC, as data are not obtained 
on calibrated devices and may not be obtained by medically trained individuals.
3.11 Vital Signs
Vital signs will be collected both supine and standing for orthostatic assessments.  For supine vital signs,
blood pressure and pulse rate will be measured after the subject has been supine for at least 5 minutes.  
For standing vital signs, blood pressure and pulse rate will be measured after the subject has been 
supine for at least 5 minutes and then after the subject has been standing for 2 minutes.  When vital 
sign measurements are scheduled at the same time as a blood collection, vital sign measurements 
should be obtained prior to blood collection.
Vital signs will be measured at the visits specified in Section 2.  Three sets of orthostatic vital sign 
assessments will be collected approximately 20 minutes apart at Visit 5.  Vital signs on Day 1 (V6) will be 
measured before randomization and also approximately 2 hours after initiation of blinded study drug 
administration prior to the end of the visit.
See Section 7.2 for criteria for PCS vital sign values.
Page 99 of 115


p. 31 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
Due to the COVID-19 pandemic, subject visits may be conducted via phone or video conference.  In 
these situations, vital signs may be obtained by the subject or caregiver as needed and recorded in the 
source. These data should not be recorded in EDC, as data are not obtained on calibrated devices and 
may not be obtained by medically trained individuals.
3.12 Physical Examination
A complete physical examination will be performed at the visits shown in Section 2.  The physical 
examination performed at V1 will serve as the baseline physical examination for clinical assessment.  A 
symptom-directed physical examination will be performed at each following visit when necessary.  Any 
significant physical examination findings after V3 will be recorded as AEs.
3.13 Neurological Examination
A neurological examination will be performed at the visits shown in Section 2.  Neurological findings 
beyond those related to PD should be reported in the eCRF.  The neurological examination performed at 
V5 will serve as the Baseline for clinical assessment.  After randomization, any significant neurological
findings will be recorded as AEs.
The neurological examination will consist of the following:

Mental Status – assessment of orientation, speech, and memory.

Cranial Nerves – assessment of cranial nerves II – XII, including a funduscopic examination.

Motor system – assessment of tone and strength.

Sensory system – brief survey for light touch and temperature.

Reflexes – assessment of deep tendon reflexes and plantar responses (Babinski sign).

Coordination – assessment of upper and lower extremities.

Gait and station
3.14 12-Lead Electrocardiogram
Single electrocardiograms (ECGs) will be recorded at the visits specified in Section 2 after the subject has 
been supine for at least 5 minutes.  Subjects will be instructed to remain stationary (no talking, laughing, 
deep breathing, sleeping, or swallowing) for approximately 10 seconds during the ECG recording.  When 
an ECG is recorded at a time near that of a blood collection, the ECG should be obtained prior to the 
blood collection.  ECGs on Day 1 (V6) will be recorded approximately 2 hours after initiation of the 
blinded study drug administration.
Clinical study personnel will transmit ECG data to an ECG central laboratory for processing and reading 
by a qualified cardiologist (central reader) who will independently review each ECG.  The central reader 
will evaluate a single ECG lead (Lead II, with V6 or V3 [in that order] evaluated if Lead II cannot be 
Page 100 of 115


p. 32 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
evaluated).  Heart rate, RR interval, PR interval, QRS duration, and QT interval will be measured for each 
ECG with 3 to 5 beats.  The QT interval corrected for heart rate (QTc) will be determined using 
Fridericia's correction method (QTcF).
The central reader will also provide the interpretation of the ECG (i.e., "normal" or "abnormal").  The 
central ECG laboratory will send the ECG report to the site within 3 business days.  The investigator (or 
physician designee) will review the central reader's report/assessment and document his/her review by 
signing and dating the central ECG laboratory report.  Only the central ECG laboratory's data will be 
collected into the database.  The investigator should review and reconcile, if necessary, his/her 
interpretation of the ECG (normal/abnormal) with the central ECG laboratory in case of relevant 
divergent assessments and reconcile as he/she determines is appropriate.
The original ECG tracing and the central reader's interpretation, each with the investigator's signature 
and date, will be retained in the subject's records at the study site as source documents.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
In the event this may not be performed due to study modifications related to the COVID-19 pandemic, 
perform the 12-lead ECG at the next earliest feasible visit or arrange to have an alternative acceptable 
local facility perform the ECG for the subject.
3.15 Clinical Laboratory Tests
Samples for clinical laboratory tests will be collected at the visits specified in Section 2.  A certified 
central laboratory will be used to process and provide results for the clinical laboratory tests.  
Laboratory reference ranges will be obtained prior to the initiation of the study.  Follow-up safety 
laboratory tests may be performed by a certified laboratory other than the site's local laboratory.
Instructions regarding the collection, processing, and shipping of these samples will be provided by the 
central laboratory via the laboratory manual.
Page 101 of 115


p. 33 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Hematology
Clinical Chemistry
Urinalysis
Hematocrit
Hemoglobin
Red blood cell (RBC) count
White blood cell (WBC) count
Neutrophils
Bands (if detected)
Lymphocytes
Monocytes
Basophils (if detected)
Eosinophils (if detected)
Absolute platelet count 
Mean corpuscular hemoglobin
Mean corpuscular volume 
concentration (MCHC)
Prothrombin time (PT)
Activated partial thromboplastin 
time
Blood urea nitrogen (BUN)
Creatininea
Creatine phosphokinase
Total bilirubin
Serum glutamic pyruvic transaminase
Serum glutamic-oxaloacetic transaminase
Lactate dehydrogenase (LDH)
Gamma-glutamyl transpeptidase
Alkaline phosphatase
Sodium
Potassium
Calcium
Inorganic phosphorus
Uric acid
Total protein
Albumin
Glucose
Sodium bicarbonate/CO2
Chloride
Triglycerides
Cholesterol
Magnesium
Special Laboratory Testsb
Vitamin B6
Vitamin B12
Folic acid
Methylmalonic acid (MMA)
Homocysteine
Specific gravity
Ketones
pH
Protein
Glucose
Blood
Bilirubin
Microscopic examination, 
if indicated
eGFR = estimated glomerular filtration rate
a.
eGFR (i.e., estimated glomerular filtration rate) will be calculated one time at Screening Visit 1 (V1) according to the 
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
b.
Special laboratory tests to detect vitamin deficiencies, i.e., vitamin B12, vitamin B6, folic acid, homocysteine, and MMA 
levels will be performed at V1, prior to randomization, and Day 85 (V13).  An abnormal vitamin B12 level of questionable 
clinical significance (indeterminate or low normal results at V1), require MMA and homocysteine laboratory assessments 
to be reviewed for determination of vitamin B12 deficiency prior to entry into the study.  If, at any time during the study, a 
subject displays symptoms of polyneuropathy, the investigator must perform this laboratory panel and any other 
assessment that the investigator feels is appropriate for further evaluation of polyneuropathy symptoms.
If a laboratory test value is outside the reference range and the investigator considers the laboratory 
result to be clinically significant, the investigator will:

repeat the test to verify the out-of-range value;

follow the out-of-range value to a satisfactory clinical resolution; or

discontinue the subject from the study or require the subject to receive treatment; in this case, 
the laboratory result will be recorded as an AE.
Page 102 of 115


p. 34 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
The investigator must evaluate all laboratory abnormalities that occur during the study to determine 
whether they indicate a new disease process, or an exacerbation or worsening of an existing condition, 
or require further action and therefore may need to be reported as AEs.  Accordingly, for any values 
outside of the reference range, the investigator will indicate on the report if the result is clinically 
significant or not clinically significant.  If a laboratory abnormality meets criteria for a potentially 
clinically significant (PCS) laboratory value, the investigator must either report an associated AE or 
document in source the reason(s) the finding was not considered an AE.  See Section 7.1.
Any laboratory value that remains abnormal at premature discontinuation/end of study and was judged 
to be clinically significant will be followed according to accepted medical standards until resolution of 
the abnormality.
Serum and Urine Pregnancy Tests
A pregnant or breastfeeding female subject will not be eligible for participation or continuation in this 
study.
Pregnancy testing is not required for females of non-childbearing potential.  Determination of 
post-menopausal status will be made during the Screening Period based on the subject's history.
A serum pregnancy test will be performed at V1 and a urine pregnancy test will be performed as shown 
in Section 2 for all women of childbearing potential.  The urine sample for the Day 1 (V6) urine 
pregnancy test will be collected prior to randomization and initiation of blinded study drug 
administration.
The serum pregnancy test will be performed by the central laboratory.  Urine pregnancy tests will be 
performed and analyzed at the site during the study visit specified in Section 2.  If a urine pregnancy test 
is positive, the results should be confirmed with a serum human chorionic gonadotropin (hCG) test that 
will be performed by the central laboratory.
If the serum pregnancy test at V1 is positive the subject is considered a screen failure.  If the result of 
the serum pregnancy test is borderline, it should be repeated to determine eligibility.
If the pregnancy test is:

Positive after serum pregnancy confirmation, the subject is considered a screen failure.

Negative, the subject can be enrolled into the study.

Still borderline, the AbbVie TA MD should be consulted.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
The urine pregnancy test may be dispensed via direct-to-patient (DTP) courier, or a family member may 
pick the test up from the site, if locally allowed and authorized.  Negative urine pregnancy test must be 
recorded by the site prior to a subject's next dose of study drug (open label CD/LC IR or blinded study 
drug).  If a urine pregnancy test is positive, the results should be confirmed with a serum hCG test. This 
may be performed by a local laboratory.
Page 103 of 115


p. 35 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Clinical Chemistry
An 8-hour fast is recommended for blood samples to be drawn for clinical chemistry.  If a subject is not 
able to fast when necessary due to unforeseen circumstances, the non-fasting status will be recorded in 
study source documentation.
Urinalysis
Urinalysis will be completed at all required visits.  Specified abnormal macroscopic urinalyses defined as 
leukocytes, nitrite, protein, ketones, or blood greater than negative, or glucose greater than normal will 
be followed up with a microscopic analysis at the central laboratory.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
If travel restrictions or other changes in local regulations in light of the COVID-19 pandemic prevent the 
subject from having blood drawn for laboratory testing at the study site, if possible, arrange for subjects 
to have laboratory work done at a local laboratory, hospital, or other facility.  Local laboratory results 
should be obtained along with reference ranges and kept within the subjects' source documentation.  
The investigator should review local laboratory results as soon as possible.
If laboratory samples cannot be obtained, study drug administration may be continued provided the 
investigator has reviewed all prior laboratory results and confirms and discusses with the subject that 
there is no safety concern for the subject to continue use of the study drug in the absence of current 
labs.  The subject should be scheduled for laboratory draws as soon as feasible.
3.16 Drug Screen
Subjects should have no history of clinically significant drug abuse within the last 6 months prior to 
screening that can preclude adherence to the protocol, in the opinion of the investigator.
Urine specimens will be tested at V1, as shown in Section 2.1, for the presence of drugs of abuse.  The 
panel for drugs of abuse will minimally include the drugs listed below.  These analyses will be performed 
by the site or by the certified central laboratory.  If the screen is performed by the site, test kits and the 
confirmation of positive results will be provided by the central laboratory.  A positive confirmation will 
result in the subject's exclusion from the study only if, in the investigator's opinion, the subject's history 
of drug abuse could preclude adherence to the protocol.  Similarly, if there is documented proof that the 
detected drug is appropriately prescribed by a physician, the subject might be enrolled in the study.

Cannabinoids

Opiates

Barbiturates

Amphetamines*

Cocaine

Benzodiazepines
Page 104 of 115


p. 36 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
*
A positive confirmation of amphetamine use, even if appropriately prescribed by a physician, will 
result in the subject's exclusion from enrollment in the study, as amphetamines are dopamine 
depleting agents and therefore prohibited in this study.
3.17 Study Drug Prescription Record
Starting at V2, with the Oral CD/LD Stabilization Period, through the end of the study as shown in 
Section 2, the subject's CD/LD IR regimen (number of tablets at each administration and dosing 
frequency) reached at the end of the Oral CD/LD Stabilization Period, pump settings (continuous 
infusion rate in mL/hour and loading dose in mL) and blinded oral study drug regimen should be 
recorded at the conclusion of each visit on the study drug prescription record.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
Due to the COVID-19 pandemic, this study activity may be performed in the subject's home by the HHN
or site staff.  The Study Drug Prescription Record is eligible for completion by interview at V3, V4, and 
V7, V8, V9, V10, V11, and V12.  In this situation, the DTP courier will confirm IP is delivered in good 
condition, and the HHN or site staff will review dosing and review the dosing regimen. During the 
Randomization Period, there is potential for the site staff or HHN to update pump settings in subject's 
home under investigator direction and delegation. Pump setting changes cannot be performed by the 
subject or caregiver.
3.18 PM-PDSC Pump Delivery System Training
AbbVie personnel, or its delegate, will train the staff at each site how to calculate each subject's LD
equivalent, to program the pump to administer the continuous dose and to titrate the dose for each 
subject as needed.  In addition, the site will be trained to prepare the Phillips-Medisize - Parkinson's 
Disease Subcutaneous (PM-PDSC) Pump Delivery System by (i) loading the study drug solution into the 
syringe, (ii) placing it into the pump, (iii) attaching the infusion set to the subject and syringe, (iv) 
priming the syringe and infusion set, and (v) operating the pump.  Clinical study personnel will receive 
the pump instructions for use for patients and the pump instructions for use for clinical study personnel.
As part of study eligibility, subjects and caregivers (if applicable) will receive training at Screening Visit 1 
(V1) on the PM-PDSC Pump Delivery System (e.g., infusion pump, infusion set, syringe, vial, vial adapter, 
and the insertion of the cannula).  In addition to training, subjects will receive training materials for 
reference. To remain eligible for study participation, the investigator or designee must assess that the 
subject and caregiver, if applicable, have demonstrated understanding and correct use of the delivery 
system, including insertion of the cannula into the subject's abdomen.
Subjects and caregivers (if applicable) may continue to be trained by site staff or nurses contracted by 
the sponsor on use of the PM-PDSC Pump Delivery System.  These nurses must be trained on how to use 
the PM-PDSC Pump Delivery System prior to training study subjects.  In addition, subjects may receive 
in-home visits from nurses to provide additional training and support with the PM-PDSC Pump Delivery 
System.  During these in-home visits, the home health care nurse may ask questions about any problems 
or concerns the subject is having using the PM-PDSC Pump Delivery System.  The home health care 
Page 105 of 115


p. 37 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
nurse will record the subject's answers and provide these to the study site for review.  Subjects may also 
have access to an after-hours call center for additional PM-PDSC Pump Delivery System support.
3.19 Study Drug and PM-PDSC Pump Delivery System Dispensation and 
Return
Open-label CD/LD IR tablets and blinded study drug (solution for infusion and capsules) will be 
dispensed throughout the study.  Subjects and/or caregivers may visit the site for CSCI solution 
dispensation and return outside of the scheduled visits.  The PM-PDSC Pump Delivery System, including 
the infusion set and other accessories, will be dispensed as needed.  AbbVie personnel or its delegates 
will train clinical study personnel on the distribution and reconciliation details.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
Study drug may be shipped from the study site directly to the study subject's home if all the following 
criteria are met:

Direct-to-patient (DTP) shipment of study drug is allowed by local regulations and the relevant 
ethics committee

Study drug can be administered by the subject (or subject's caregiver) at home

Subject agrees to have the study drug shipped directly to their home

Shipments may also include other study supplies (e.g., drug dosing diaries, paper copies of 
PROs, urine pregnancy tests, PD-PMSC ancillary supplies).  Instructions will be provided by 
AbbVie as to how a study site can initiate a DTP shipment using Marken, a global vendor 
selected by AbbVie to provide this service when necessary.  Shipments of study drugs from 
the study site to a subject's home will be appropriately temperature controlled (qualified 
shipper or temperature monitoring) within the labeled storage conditions.  Signature is 
required upon delivery; due to COVID-19-related social distancing, this may be provided by 
the courier after delivery.  Documentation of the shipment is to be retained by the clinical 
site.

AbbVie will not receive subject identifying information related to these shipments, as the 
site will work directly with the courier.
The study site is responsible for meeting IRB/IEC reporting requirements related to DTP shipments of 
study drug and for obtaining consent to provide delivery information to the courier and documenting 
this consent in source documents.
The subject and/or caregiver will be instructed on how to return all study drug, devices, and ancillaries.  
Clinical study personnel will document compliance.
3.20 Subject Withdrawal from Study
All attempts must be made to determine the last day of study drug and the reason(s) for discontinuation 
of study drug or study participation.  The information will be recorded on the appropriate eCRF page; 
Page 106 of 115


p. 38 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
however, these procedures should not interfere with the initiation of any new treatments or therapeutic 
modalities that the investigator feels are necessary to treat the subject's condition.  Following 
discontinuation of study drug, the subject will be treated in accordance with the investigator's best 
clinical judgment, irrespective of whether the subject decides to continue participation in the study.
3.21 Home Healthcare Service Due to COVID-19 Pandemic
In addition to the HHN service to support PM-PDSC system training for the study, subjects may be 
offered the option for the HHN to perform delegated study activities.  Study procedures conducted in 
the home setting may include those indicated in Sections 2 and 3.  These activities may include, but are 
not limited to, programming the study pump to adjust the flow rate under the delegation of the 
investigator, verifying the supply of study drug, PM-PDSC Pump Delivery System, and ancillaries.
This option can only be offered in countries and sites that comply with local regulatory and IRB/IEC 
requirements for homecare.  Any pre-requisite submissions or notifications to the site IRB/IEC and local 
competent health authority should be made and approvals must be obtained prior to implementation of 
home infusions.
For Studies with IP Infusions:
Finally, it is recommended that medical personnel entering a subject's home adhere to local health 
regulations during the COVID-19 pandemic, such as the use of personal protective equipment (PPE), as 
required.
Protocol deviations must be recorded per AbbVie's standard process.
If the home visits will not be performed by site personnel or the sponsor-provided HHN, the site may be 
responsible for selecting a vendor, contracting with a vendor, and for ensuring continued compliance 
with the terms of the Clinical Study Agreement.
Individuals performing home visits need to be added to the delegation log.  If utilizing a vendor, the 
delegation of authority log provided by the vendor may be required to be used for the nurses supplied 
by the vendor.  The principal investigator must ensure that any staff performing drug infusions are 
qualified and trained to do so per local regulations.
4 SAFETY MANUAL
4.1 Methods and Timing of Safety Assessment
All SAEs and nonserious adverse events (AEs) that could be related to study procedures will be collected 
from the time the subject signed the study-specific informed consent until study drug administration.  
From the time of study drug administration (V3) until 30 days after discontinuation of study drug 
treatment, all AEs and SAEs will be collected whether solicited or spontaneously reported by the subject.  
After 30 days following completion of study treatment, all spontaneously reported SAEs will be collected 
(nonserious AEs will not be collected).
Page 107 of 115






p. 41 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
If a subject has a confirmed or suspected COVID-19 infection and study drug was interrupted, the 
investigator should contact the sponsor emergency medical contact listed above before reintroducing 
study drug.
4.3 Product Complaint Reporting
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 24 hours of the study site's knowledge of the event.  Product complaints occurring during the 
study will be followed to a satisfactory conclusion.
All follow-up information is to be reported to the sponsor (or an authorized representative) and 
documented in source as required by the sponsor.  Product complaints associated with AEs will be 
reported in the study summary.  All other complaints will be monitored on an ongoing basis.
Product complaints may require return of the product with the alleged complaint condition (infusion 
pump, infusion set, etc.).  In instances where a return is requested, every effort should be made by the 
investigator to return the product within 30 days.  If returns cannot be accommodated within 30 days, 
the site will need to provide justification and an estimated date of return.
The description of the complaint is important for AbbVie in order to enable AbbVie to investigate and 
determine if any corrective actions are required (refer to Protocol Section 6.1, Complaints and Adverse 
Events for details).
5 COUNTRY-SPECIFIC REQUIREMENTS
5.1 SUSAR Reporting
AbbVie will be responsible for Suspected Unexpected Serious Adverse Reactions (SUSAR) reporting for 
the Investigational Medicinal Product (IMP) in accordance with global and local guidelines and 
Appendix A of the Investigator Brochure will serve as the Reference Safety Information (RSI).  The RSI in
effect at the start of a Development Safety Update Report reporting period serves as the RSI during the 
reporting period.  For follow-up reports, the RSI in place at the time of occurrence of the "suspected" 
Serious Adverse Reaction will be used to assess expectedness.
5.2 Treatment After End of Study
At the end of the study, subjects may continue on study treatment as part of an open-label extension 
study.  At the subject's last study visit, the investigator will discuss appropriate subsequent treatment 
with the subject.
6 References
1.
US Dept of Health and Human Services Food and Drug Administration Center for Drug 
Evaluation and Research (CDER).  Guidance for Industry:  Skin Irritation and Sensitization Testing 
of Generic Transdermal Drug Products.  December 1999.
Page 110 of 115










p. 46 of 46
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M15-736 Version 5.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
7.2 CRITERIA FOR POTENTIALLY CLINICALLY SIGNIFICANT VITAL SIGN 
AND WEIGHT VALUES
Variable Measured
Potentially Clinically Significant (PCS) Value
Systolic blood pressure decreased
≤ 80 mmHg and ≤ 45 mmHg below baseline value
Systolic blood pressure increased
≥ 160 mmHg and ≥ 45 mmHg above baseline value
Orthostatic systolic blood pressure
≥ 30 mmHg decrease from supine to standing
Diastolic blood pressure decreased
≤ 50 mmHg and ≤ 40 mmHg below baseline value
Diastolic blood pressure increased
≥ 95 mmHg and ≥ 40 mmHg above baseline value
Orthostatic diastolic blood pressure
≥ 20 mmHg decrease from supine to standing
Pulse rate decreased
≤ 45 bpm and ≤ 35 bpm below baseline value
Pulse rate increased
≥ 120 bpm and ≥ 35 bpm above baseline value
Temperature increased
≥ 38.3°C and ≥ 1.1°C above baseline value
Weight decreased
≥ 7% decrease from baseline value
Weight increased
≥ 7% increase from baseline value
bpm = beats per minute
Page 115 of 115

SAP_001.pdf: 
ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
1
Statistical Analysis Plan for Study M15-736
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
Date:  19 October 2021
Version 3.0
NCT04380142


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
2
Table of Contents
1.0
Introduction .............................................................................5
2.0
Study Design and Objectives..................................................5
2.1
Objectives and Hypotheses ........................................................................5
2.2
Study Design Overview .............................................................................6
2.3
Treatment Assignment and Blinding .........................................................8
2.4
Sample Size Determination........................................................................9
3.0
Endpoints..................................................................................9
3.1
Primary Endpoint.......................................................................................9
3.2
Secondary Endpoints ...............................................................................10
3.3
Other Efficacy Endpoints.........................................................................11
3.4
Safety Endpoints ......................................................................................11
3.5
Endpoints During the Oral CD/LD Stabilization Period .........................12
4.0
Analysis Populations .............................................................12
5.0
Subject Disposition................................................................13
6.0
Study Drug Duration and Compliance................................15
7.0
Demographic and Baseline Clinical Characteristics, 
Medical History, Prior/Concomitant Medications 
and Dosing..............................................................................16
7.1
Demographic and Baseline Clinical Characteristics................................16
7.2
Medical History .......................................................................................17
7.3
Prior and Concomitant Medications ........................................................17
7.4
Analysis of Dosing...................................................................................18
7.4.1
Analysis of Daily Prescribed Dose ..........................................................18
7.4.2
Analysis of Initial Optimization...............................................................19
7.4.3
Analysis of Daily Levodopa Dose ...........................................................19
7.4.4
Other Dosing Analysis.............................................................................20
7.5
Other Descriptive Analyses .....................................................................20
8.0
Efficacy Analyses...................................................................20
8.1
General Considerations............................................................................20
8.2
Handling of Missing Data........................................................................22
8.2.1
Handling of Missing Items in Efficacy Instruments................................22


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
3
8.2.2
Handling of Intercurrent Events and Missing Visit Values in 
Efficacy Endpoints...................................................................................23
8.3
Primary Efficacy Endpoint and Analyses ................................................25
8.3.1
Primary Efficacy Endpoint ......................................................................25
8.3.2
Primary Efficacy Analysis .......................................................................25
8.3.3
Additional Analyses of the Primary Efficacy Endpoints.........................27
8.4
Secondary Efficacy Analyses...................................................................28
8.4.1
Key Secondary and Other Secondary Efficacy Analyses ........................28
8.4.2
Other Efficacy Analyses ..........................................................................29
8.5
Efficacy Analyses During the Oral CD/LD Stabilization Period ............30
8.6
Efficacy Subgroup Analyses....................................................................30
9.0
Safety Analyses ......................................................................31
9.1
General Considerations............................................................................31
9.2
Adverse Events ........................................................................................32
9.2.1
Treatment-Emergent Adverse Events ......................................................32
9.2.2
Adverse Event Overview .........................................................................33
9.2.3
Treatment-Emergent Adverse Events by SOC and/or PT .......................35
9.2.4
Adverse Event by Maximum Severity.....................................................35
9.2.5
Adverse Event by Relationship to Study Drug ........................................36
9.2.6
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure ..................................................................................................36
9.2.7
Adverse Events of Special Interest ..........................................................36
9.2.8
Adverse Event by Relationship to Product Quality Complaints..............37
9.2.9
Adverse Event Leading to Study Drug Discontinuation, 
Interruption, and Dose Reduction............................................................38
9.2.10
Adverse Event Associated with Rescue Medication................................38
9.2.11
Serious Adverse Events ...........................................................................38
9.2.12
TEAE identified by Abuse Liability Company MedDRA Query............38
9.2.13
COVID-19 related Adverse Events..........................................................39
9.2.14
Listings of Adverse Events ......................................................................39
9.3
Safety Subgroup Analyses .......................................................................39
9.4
Analysis of Laboratory Data....................................................................40
9.5
Analysis of Vital Signs ............................................................................41


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
4
9.6
Other Safety Analyses..............................................................................43
9.6.1
Analysis of ECG Parameters....................................................................43
9.6.2
Infusion Site Evaluation Scale.................................................................44
9.6.3
Analysis of Questionnaire for Impulsive-Compulsive Disorders in 
PD-Rating Scale (QUIP-RS)....................................................................44
9.6.4
Analysis of Columbia-Suicide Severity Rating Scale (C-SSRS) ............45
10.0
Interim Analyses....................................................................45
11.0
Overall Type I Error Control...............................................45
12.0
Version History......................................................................47
13.0
References...............................................................................49
List of Tables
Table 1.
Summary of Primary and Sensitivity Analysis for the Primary 
Efficacy Endpoint of Change from Baseline to Week 12 in 
Average Daily Normalized "On" Time Without Troublesome 
Dyskinesia and other "On" times as well as "Off" time derived 
from the PD Diary....................................................................................28
Table 2.
SAP Version History Summary...............................................................47
List of Figures
Figure 1.
Study Design Schematic ............................................................................7
List of Appendices
Appendix A.
Protocol Deviations..................................................................................50
Appendix B.
Definition of Adverse Events of Special Interest ....................................51
Appendix C.
Potentially Clinically Significant Criteria for Safety Endpoints..............52


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
5
1.0
Introduction
This Statistical Analysis Plan (SAP) describes the statistical analyses for ABBV-951 
Study M15-736 "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."
The SAP will not be updated in case of administrative changes or amendments to the 
protocol unless the changes impact the analysis.
Unless stated otherwise, all analyses will be performed using SAS Version 9.2 (SAS 
Institute Inc., Cary, NC  27513) or later under the UNIX operating system.
This SAP includes changes to analyses described in the protocol.  Details are outlined in 
Section 12.0.
2.0
Study Design and Objectives
2.1
Objectives and Hypotheses
The primary objective of the study is to demonstrate the superiority of continuous 
subcutaneous infusion (CSCI) of ABBV-951 over oral carbidopa/levodopa (CD/LD) 
immediate release (IR) tablets for the treatment of motor fluctuations in subjects with 
advanced Parkinson's disease (aPD) after 12 weeks of therapy.
Clinical Hypothesis:  The 24-hour/day CSCI of ABBV-951 will increase "On" time 
without troublesome dyskinesia ("On" time without dyskinesia plus "On" time with non-
troublesome dyskinesia), reduce "Off" time, and improve the Motor Aspects of 
Experiences of Daily Living compared to CD/LD IR tablets in patients with aPD whose 
motor fluctuations are inadequately controlled by their current PD medications.
The secondary objective of the study is to assess the local and systemic safety and 
tolerability of ABBV-951 delivered as a CSCI for 24 hours daily for 12 weeks.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
6
Subject must be judged to be inadequately controlled by current therapy in the
investigator's opinion and 
●
experience a minimum daily average of 2.5 hours of "Off" time (with a
minimum of 2 hours of "Off" time each day) as assessed by PD Diary for 3 
consecutive days prior to V3 (Enrollment Visit)
AND
●
maintain at least 2 hours of "Off" time each day for 3 consecutive days before 
V6 (Randomization Visit).
2.2
Study Design Overview
The schematic of the study is shown in Figure 1.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
7
Figure 1.
Study Design Schematic
CD/LD = carbidopa/levodopa; CSCI = continuous subcutaneous infusion; D = Day; IR = immediate release; 
PD = Parkinson's disease; V = Visit 
a.
V3 can occur at least 6 days after V1 to allow for V1 results to be fully available for review and for adequate 
infusion delivery system training and familiarity.
b.
Screening Period activities will last at least 6 days; PD Diaries will be collected for at least 3 consecutive days 
during the Screening Period prior to V3; collection of PD Diaries may be repeated only once for 3 additional 
consecutive days leading up to V3 prior to the start of the Oral CD/LD Stabilization Period.
c.
The activities of the Oral CD/LD Stabilization Period are expected to take 14 to 21 days to accommodate 
scheduling, additional unscheduled visits, and, when allowed, repeated assessments.  PD Diaries will be collected 
for at least 3 consecutive days before Day -1.
d.
If a subject prematurely discontinues study participation or completes the study and does not enter the open-label 
extension Study M20-098, a follow-up visit or follow-up phone call will be completed 30 days after the last day of 
study drug, if the subject is willing, to ensure all treatment-emergent AEs/SAEs have resolved.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
8
Screening Period
This 6- to 60-day period consists of 2 screening visits (V1 and V2).
Oral CD/LD Stabilization Period
This 14-to 21-day period consists of 3 visits (V3, V4, and V5).  V4 is an optional visit.  
V5 is the Baseline Visit for the majority of assessments.
Double-Blind Treatment Period
This 12-week period starts with initiation of blinded study drug solution and blinded oral 
capsule and consists of 2 parts: a 4-week CSCI Optimization Phase and an 8-week 
Maintenance Phase.
Post-treatment Period Activities
There are no post-treatment activities except for subjects who prematurely discontinue 
study participation.  See Protocol Section 5.7 for additional information.
2.3
Treatment Assignment and Blinding
At the end of the Oral CD/LD Stabilization Period, eligible subjects will be randomized in 
a 1:1 ratio to one of the two treatment arms for the 12-week Double-Blind Treatment 
Period:
●
24-hour/day CSCI of ABBV-951 plus oral placebo capsules for CD/LD IR 
(also referred to as investigational group or ABBV-951 group in this document)
OR
●
24-hour/day CSCI of placebo solution for ABBV-951 plus oral encapsulated 
CD/LD IR tablets (also referred to as active control group or Oral CD/LD 
group in this document)
Randomization will be stratified by study site with a block size of 2.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
9
The first day of the blinded study drug administration is defined as Day 1.
To help evaluate maintenance of the blind, an exit interview will be conducted when 
subjects prematurely discontinue from the study or when subjects complete the study. 
The data collected during the exit interview will be summarized. 
2.4
Sample Size Determination
Assuming that the difference in change from Baseline to Week 12 in average daily 
normalized "On" time without troublesome dyskinesia is 1.86 hours between the 
investigational group and the active control group, and the common standard deviation is 
2.9 hours, a sample size of 52 subjects per arm will have 90% power to detect a 
statistically significant difference between the 2 treatment arms with a 2-sided 
significance level of 0.05 (using nQuery Version 8.4.0.0).  Approximately 130 subjects 
will be randomized assuming that approximately 20% of subjects will prematurely 
discontinue blinded study drug during the Double-Blind Treatment Period.  This sample 
size also has approximately 90% power for key secondary endpoints of change from 
baseline in average daily normalized "Off" time, Movement Disorder Society-Unified 
Parkinson's Disease Rating Scale (MDS-UPDRS) Part II score and presence of morning 
akinesia at Week 12 ("Off" status as the first morning symptom upon awakening).
An adequate number of subjects will be enrolled in the Oral CD/LD Stabilization Period 
to meet the randomization goal of the study.
3.0
Endpoints
3.1
Primary Endpoint
The primary efficacy endpoint is the change from Baseline to Week 12 of the Double-
Blind Treatment Period in average daily normalized "On" time without troublesome 
dyskinesia (hours) as assessed by the PD Diary.  Baseline value definition details are 
provided in Section 8.1 and Section 8.2.1.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
10
3.2
Secondary Endpoints
The following key secondary and other secondary endpoints of the Double-Blind 
Treatment Period will be included in multiplicity adjustment of the Type I error to control 
the familywise error rate (FWER) at 2-side significance level of 0.05 for the entire study.  
These variables will be tested in the following fixed sequence as a gatekeeping procedure.
●
Key secondary endpoints:
○
Change from Baseline to Week 12 in hours of average daily normalized 
"Off" time as assessed by the PD diary.
○
Change from Baseline to Week 12 in Motor Aspects of Experiences of 
Daily Living as assessed by the MDS-UPDRS Part II score. 
○
Presence of morning akinesia at Week 12 (defined as reporting "Off" status 
as the first morning symptom upon awakening) as assessed by the PD 
Diary.
●
Other secondary endpoints included in FWER control:
○
Change from Baseline to Week 12 in hours of average daily normalized 
"On" time without dyskinesia as assessed by the PD Diary.
○
Change from Baseline to Final Visit in sleep symptoms as assessed by 
Parkinson's Disease Sleep Scale-2 (PDSS-2) total score
○
Change from Baseline to Final Visit in PD-related quality of life as 
assessed by the Parkinson's Disease Questionnarie-39 Item (PDQ-39) 
summary index
○
Change from Baseline to Final Visit in health-related quality of life as 
assessed by the EQ-5D-5L summary index
○
Change from Baseline to Week 12 in median bradykinesia score (BK50) as 
assessed by the Parkinson's KinetiGraph™/Personal KinetiGraph™ (PKG) 
wearable device 
○
Change from Baseline to Week 12 in interquartile range of bradykinesia 
score (BK75-BK25) as assessed by the PKG wearable device
○
Change from Baseline to Week 12 in median dyskinesia score (DK50) as 
assessed by the PKG wearable device


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
11
○
Change from Baseline to Week 12 in interquartile range of dyskinesia 
score (DK75-DK25) as assessed by the PKG wearable device
3.3
Other Efficacy Endpoints
The primary and secondary efficacy endpoints included in multiplicity adjustment of the 
FWER are listed in Section 3.1 and Section 3.2, respectively.  The additional efficacy 
endpoints during the Double-Blind Treatment Period are:
●
Percent change from Baseline to Week 12 in time of tremor and daytime 
somnolence as assessed by the PKG wearable device
●
Change from Baseline to Week 12 in MDS-UPDRS Part I score, Part III score, 
Part IV score, and total score of Parts I - III
●
Change from Baseline to Week 12 in average daily normalized "On" time with 
non-troublesome dyskinesia, and "On" time with troublesome dyskinesia as 
assessed by the PD Diary
●
Percent change from Baseline to Week 12 in average daily normalized "Off"
time, "On" time without troublesome dyskinesia, "On" time without dyskinesia, 
"On" time with non-troublesome dyskinesia, and "On" time with troublesome 
dyskinesia as assessed by the PD Diary
●
Change from Baseline to Week 12 in average daily absolute "Off" time, "On"
time without troublesome dyskinesia, "On" time without dyskinesia, "On" time 
with non-troublesome dyskinesia, "On" time with troublesome dyskinesia, and 
"Asleep" time as assessed by the PD Diary without normalizing
●
Change from Baseline to Final Visit in PDSS-2 domain scores
●
Change from Baseline to Final Visit in PDQ-39 domain scores
●
Change from Baseline to Final Visit in EQ-5D-5L visual analogue scale (VAS) 
score
3.4
Safety Endpoints
Safety endpoints are:


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
12
●
Adverse events (AEs), serious AEs (SAEs) and AEs of special interest (AESIs)
●
Local tolerability as measured by the Infusion Site Evaluation scale
●
Clinical laboratory values
●
Vital signs
●
Electrocardiograms (ECG) 
●
The Columbia-Suicide Severity Rating Scale (C-SSRS) 
●
The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-
Rating Scale (QUIP-RS)
3.5
Endpoints During the Oral CD/LD Stabilization Period
The following variables for the Oral CD/LD Stabilization Period will be summarized:
●
Change from Screening value to study Baseline (prior to randomization) in 
average daily normalized "Off" time, "On" time without troublesome 
dyskinesia, "On" time without dyskinesia, "On" time with non-troublesome 
dyskinesia, and "On" time with troublesome dyskinesia as assessed by the PD 
Diary
●
Change from Screening value to study Baseline (prior to randomization) in PD 
symptoms (including tremor, bradykinesia, dyskinesia, and daytime 
somnolence) as assessed by the PKG wearable device
4.0
Analysis Populations
The following analysis sets will be used for analyses.
The Oral CD/LD Analysis Set includes all subjects who received at least 1 dose of open-
label CD/LD IR tablets during the Oral CD/LD Stabilization Period.  The Oral CD/LD 
Analysis Set will be used to summarize premature discontinuations, and adverse events 
during the Oral CD/LD Stabilization Period.
The Full Analysis Set (FAS) includes all randomized subjects who received any dose of 
study drug during the Double-Blind Treatment Period and who have baseline and at least 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
13
1 post-baseline observation for at least 1 efficacy assessment.  The FAS will be used for 
all efficacy analyses unless stated otherwise.  Subjects will be included in the analysis 
according to the treatment group to which they were randomized.
The Safety Analysis Set consists of all subjects who received any dose of study drug 
during the Double-Blind Treatment Period.  The Safety Analysis Set will be used for all
demographic, baseline, and safety analyses unless stated otherwise.  Subjects will be 
included in the analysis according to the study drug that they actually received regardless 
of randomization.  It is unlikely that a subject will receive a wrong study drug kit due to 
dispensing errors.  If that happens, the various scenarios that could occur are following:
●
Double placebo (placebo solution + placebo capsule): The subject will be 
included in the active treatment group that they received regardless of 
randomization or duration on placebo.
●
Double active (ABBV-951 + CD/LD capsule): The subject will be included in 
the active treatment group that they received for >50% of the time regardless of 
randomization.
●
Wrong kits resulting in the exact opposite of assigned treatment, i.e.,
○
Oral CD/LD group (placebo solution + CD/LD capsule) subject was 
dispensed ABBV-951 solution and placebo capsule
OR
○
ABBV-951 group (ABBV-951 solution + placebo capsule) subject was 
dispensed placebo solution and CD/LD capsule
●
The subject will be included in the active treatment group that they received for 
>50% of the time regardless of randomization.
5.0
Subject Disposition
The total number of subjects who were screened, entered Oral CD/LD Stabilization 
Period, randomized, and received blinded study drug will be summarized.  Reasons for 
exclusion, including screen failure, will be summarized.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
14
A summary of subject accountability will be provided where the number of subjects in 
each of the following categories will be summarized by dose subgroup (low dose or high 
dose) within each treatment group:
●
Subjects enrolled in the Oral CD/LD Stabilization Period;
●
Subjects who prematurely discontinued during the Oral CD/LD Stabilization 
Period (all reasons and primary reason);
●
Subjects randomized;
●
Subjects who took any dose of blinded study drug;
●
Subjects who completed the Double-Blind Treatment Period;
●
Subjects who prematurely discontinued blinded study drug during the Double-
Blind Treatment Period (all reasons and primary reason);
●
Subjects who prematurely discontinued study participation during the Double-
Blind Treatment Period (all reasons and primary reason);
●
Subjects in each analysis set.
Each subject will be categorized to a dose subgroup based on the modal total daily dose 
over the treatment period.  The calculation of modal total daily dose is defined in 
Section 7.4.3.
A listing of all subjects affected by the COVID-19 related study disruption by subject 
number and by site ID, and a description of how the subject's participation was altered 
because of Covid-19:
●
Subjects prematurely discontinued study drug
●
Subjects prematurely discontinued from study
●
Study drug interrupted
●
Subjects missed a visit
●
Subjects conducted virtual visit


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
15
6.0
Study Drug Duration and Compliance
For the Safety Analysis Set, duration of treatment will be summarized by dose subgroup 
(low dose or high dose) within each treatment group and for both treatment groups 
combined.  Duration (days) of the double-blind treatment is defined for each subject as 
last dose date minus first dose date plus 1.  Duration of treatment will be summarized 
using the number of subjects treated, mean, standard deviation, median, minimum, and 
maximum.  In addition, the number and percentage of subjects in each treatment duration 
interval (1 to 7, 8 to 14, 15 to 28, 29 to 56, and > 56 days) will be summarized.
For each subject, percent treatment compliance for both study drug solution and study 
drug capsules will be calculated and is defined as
●
Study drug solution (ABBV-951 CSCI or placebo solution CSCI):  calculated 
as the number of hours the pump is infusing relative to the 24-hour/day goal 
and averaged over valid dosing diary days.
●
Study drug capsules (placebo capsules or encapsulated CD/LD 25/100 mg IR 
tablets):  calculated as the actual study drug capsules taken relative to the 
number prescribed and averaged over valid dosing diary days.
A valid dosing diary day is defined as one in which the pump infuses (ABBV-951 or 
placebo solution) ≥ 80% of the entire 24-hour period (i.e., ≥ 19.2 hours).
Percent treatment compliance will be summarized for the entire Double-Blind Treatment 
Period by treatment group and for both groups combined for the Safety Analysis Set using 
the number of subjects with non-missing observations, mean, standard deviation, median, 
minimum, and maximum.
Rescue medication is defined as the use of open-label CD/LD IR tablets while the subjects 
are on blinded study drug during the Double-Blind Treatment Period.  The average daily 
levodopa dose from blinded study drug, from rescue medication, and the total of blinded 
study drug and rescue medication will be calculated for each visit that the dosing diary is 
collected.  The average daily levodopa equivalent dose (LED) from all PD medications 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
16
(blinded study drug, loading dose, rescue medication, and concomitant PD medications) 
will also be calculated using conversion factors for each PD medication (Tomlinson et al 
20101) for each visit that the dosing diary is collected.  The average daily levodopa dose 
and average daily LED will be summarized by treatment group and for both groups 
combined for the Safety Analysis Set using the number of subjects with non-missing 
dosing diaries, mean, standard deviation, median, minimum, and maximum.
7.0
Demographic and Baseline Clinical Characteristics, 
Medical History, Prior/Concomitant Medications 
and Dosing
Demographic and baseline clinical characteristics, medical history, and prior and 
concomitant medications will be summarized by dose subgroup (low dose or high dose) 
within each treatment group and the Safety Analysis Set overall.  Each subject will be 
categorized to a dose subgroup based on the modal total daily dose over the treatment 
period.  The calculation of modal total daily dose is defined in Section 7.4.3.
Categorical variables will be summarized with the number and percentage of subjects; 
percentages will be calculated based on the number of non-missing observations.  
Continuous variables will be summarized with descriptive statistics (number of non-
missing observations, mean and standard deviation, median, minimum, and maximum).
7.1
Demographic and Baseline Clinical Characteristics
Continuous demographic and clinical variables are age, weight, height, body mass index 
(BMI), Mini-Mental State Examination (MMSE) score, baseline levodopa dose, and 
baseline LED.  Categorical demographic and clinical variables are sex, ethnicity, race, age 
category (< 50, 50 to < 65, 65 to < 75, or ≥ 75 years), BMI (< 18.5, 18.5 - < 25.0, 25.0 -
< 30.0, ≥ 30.0), country, tobacco user (current, former, never, unknown), alcohol user 
(current, former, never, unknown), and all Brief Neurological Examination variables.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
17
7.2
Medical History
Medical history data will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).  The actual version of the MedDRA used will be specified in the statistical 
tables and clinical study report.  The number and percentage of subjects in each medical 
history category (by MedDRA system organ class [SOC] and preferred term [PT]) will be 
summarized overall and by treatment group.  The SOC will be presented in alphabetical 
order, and PTs will be presented in alphabetical order within each SOC.  Subjects who 
report more than one condition/diagnosis will be counted only once in each row (SOC or 
PT).
Parkinson's Disease history will be summarized with the following variables:
●
Continuous variables:  age at PD onset (years), duration of PD since symptom 
onset (years), age at PD diagnosis (years), duration of PD since diagnosis 
(years), age at onset of motor fluctuation (years), duration since onset of motor 
fluctuation (years).
●
Categorical variables:  duration of PD since diagnosis (< 10 years, ≥10 years), 
history of levodopa induced dyskinesia (Yes, No), levodopa response for more 
than 5 years (Yes, No), and Hoehn and Yahr Stage.
7.3
Prior and Concomitant Medications
Prior and concomitant PD medications and non-PD medications will be summarized 
separately.  A prior medication is defined as any medication taken prior to the start of the 
Oral CD/LD Stabilization Period.  A concomitant medication during the Double-Blind 
Treatment Period is defined as any medication that started prior to the date of the first 
dose of blinded study drug and continued to be taken after the first dose of study drug or 
any medication that started on or after the date of the first dose of study drug, but not after 
the date of the last dose of study drug.  The number and percentage of subjects taking 
medications will be summarized by ATC level 3, ATC level 4, and by generic drug name 
based on the World Health Organization (WHO) Drug Dictionary for both prior and 
concomitant PD medications.  The number and percentage of subjects taking medications 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
18
will be summarized by ATC level 3 and by generic drug name based on the WHO Drug 
Dictionary for non-PD medications.
PD medications used at Screening (on the day prior to the start of open-label study drug of 
the Oral CD/LD Stabilization Period) and at Baseline (on Day -2) will be summarized 
●
By the number of classes of PD medications taken for all subjects overall and 
by treatment group.
●
In the following categories
○
LD alone
○
LD + only concomitant dopaminergic agonists
○
LD + only concomitant MAO-B inhibitor
○
LD + only istradefylline
○
LD + only any amantadine formulation
○
LD + 2 different classes of Parkinson's disease drugs
○
LD + 3 different classes of Parkinson's disease drugs
7.4
Analysis of Dosing
Based on molecular weight, 100 mg of levodopa phosphate (LDP) is equivalent to 71 mg 
of levodopa. Unless otherwise stated, all study drug doses will be presented as LD 
equivalents.
Unless otherwise stated, all analyses of dosing diary data will be performed on valid 
dosing diary days.
7.4.1
Analysis of Daily Prescribed Dose
Summary statistics (mean, SD, median, minimum, and maximum) will be provided for 
prescribed dose information, including loading dose and continuous infusion rates for the 
investigation group, and oral levodopa dose (from encapsulated CD/LD IR) for the active 
control group.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
19
When available, the summary statistics will be provided at initial prescription, first 
maintenance prescription following the Optimization Phase, final prescription in the 
8-week Maintenance Phase, and final prescription in study.  Change from initial to first 
maintenance, initial to maintenance final, initial to final and maintenance first to final will 
also be summarized.
7.4.2
Analysis of Initial Optimization
Duration of initial optimization of pump infusion rate is defined as the number of days 
from Day 1 to the first day where there is no change to the infusion rate setting on the 
pump for at least 7 days.
Duration of initial optimization will be summarized by the following interval (days):  1, 2, 
3, 4, 5, 6, 7, 8 - 14, 15 - 21, 22 - 28, and > 28.  When applicable, the summary statistics 
will include mean, SD, median, minimum, and maximum.
7.4.3
Analysis of Daily Levodopa Dose
Daily levodopa dose will be summarized for blinded study drug and open-label oral 
CD/LD IR tablet at each protocol defined visit.  Summary statistics are mean, SD, 
median, minimum, and maximum.
The modal total daily levodopa dose during the study will be determined for each subject 
by first assigning the subject's total daily levodopa doses to narrow dose ranges in 100-mg 
increments (e.g., 1000 to < 1100 mg, 1100 to < 1200 mg) and then selecting the most 
frequent narrow dose range for the subject.  If 2 or more dose ranges are of the same 
highest frequency, the highest dose range will be selected.
The modal continuous pump infusion rate for the ABBV-951 treatment group will be 
similarly defined for each subject.
The modal total daily dose will be summarized for the Safety Analysis Set.  The modal 
pump infusion rate will be summarized for the ABBV-951 treatment group in the Safety 
Analysis Set.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
20
7.4.4
Other Dosing Analysis
The frequency of subjects taking rescue medication will be summarized by 0 time, 1 time, 
2 times and ≥ 3 times categories and by the following study day intervals:  1 - 7, 8 - 14, 
15 - 21, 22 - 28, 29 - 42, ≥ 43.  In addition, the number of subjects with at least 
one occurrence and the total number of occurrences will be summarized by mean, SD, 
median, minimum, and maximum.
7.5
Other Descriptive Analyses
A summary of protocol deviations will be provided.
8.0
Efficacy Analyses
8.1
General Considerations
All efficacy analyses will be conducted on the FAS.  All tests will be 2-sided at an alpha 
level of 0.05.
The Primary Analysis will be performed after all subjects have completed the Double-
Blind Treatment Period and the database has been locked.
Unless otherwise specified, continuous variables will be analyzed using the Mixed-Effect 
Model Repeat Measurement (MMRM) method.
Baseline for PD Diary variables will be the average of the 3 valid diaries completed 
before Day -1.  Baseline for all efficacy measures, other than the PD Diary, will be 
defined as the last non-missing observation that is before the day of initiation of double-
blinded study drug.
Post-baseline efficacy and safety measures, other than AE and Infusion Site Evaluation, 
collected more than 1 day after the last dose of double-blind study drug will not be used 
for efficacy and safety analyses because data after discontinuation of study drug may be 
confounded by the various PD treatments that the subjects may be on after discontinuing 
study treatment.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
21
Variables Derived from PD Diary
The primary, 2 of the key secondary and several other secondary efficacy variables will be 
obtained from the PD Diary.  On PD Diary recording days, the subject will be instructed 
to make an entry upon awakening from time asleep and every 30 minutes during their 
normal waking time for a full 24-hour period of each day from 12:00am to 11:30pm (48 
entries, with each entry representing 0.5 hours).  Each entry could be in one of 5 
categories:  Asleep, "Off," "On" without dyskinesia, "On" with non-troublesome 
dyskinesia, and "On" with troublesome dyskinesia.  For each diary day, the absolute time 
spent in each category will be summed.  The daily awake time will be the sum of the 
absolute time spent in the 4 non-asleep categories.  Daily "Off" and "On" times will be 
normalized to a typical waking day (16 hours) to account for different sleep patterns 
across subjects, e.g.,
Normalized "On" time without troublesome dyskinesia = (Absolute "On" time without 
troublesome dyskinesia/Awake time) × 16
Daily normalized "Off" and "On" times are averaged over valid PD Diary days for each 
visit to obtain the average daily normalized "Off" and "On" times.  A valid PD Diary day 
is defined in Section 8.2.1.
First morning status upon awakening is determined by examining the PD Diary entries 
between 0:00 am and 12:00 pm on the last valid PD Diary day.  First morning status upon 
awakening is defined as the first non-sleep and non-missing entry on the PD Diary after at 
least 4 consecutive entries of "Asleep" (i.e., at least 2 hours of continuous sleep).


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
22
8.2
Handling of Missing Data
8.2.1
Handling of Missing Items in Efficacy Instruments
PD Diary
A valid PD Diary day is defined as one within 7 days prior to a clinical visit but not on or 
after the day of the visit and with no more than 2 hours of missing data (4 or fewer 
missing 30-minute entries) for the entire 24-hour diary.
For Baseline, a valid PD Diary day also cannot be on the day prior to the Randomization 
Visit (V6) because the subjects are asked not to take any PD medications for at least 12 
hours before V6.
An invalid PD Diary day will not be used in the calculation of the average daily 
normalized or absolute "Off" or "On" times for the visit it is associated with.
If more than 3 valid PD Diary days are available for Baseline or post-baseline visits, the 
3 days closest to the clinical visit will be used.  If only 2 valid PD Diary days are available 
prior to a clinic visit, data from the 2 days will be used to calculate the average daily 
normalized "Off" or "On" times.  If only 1 valid PD Diary day is available, the value from 
the 1 valid PD Diary day will be the visit value.  If no valid PD Diary day is available for 
a visit, the average daily normalized "Off" or "On" times will be missing for that visit.
MDS-UPDRS
The MDS-UPDRS total score and score of each part will be calculated as long as no more 
than 15% of the answers are missing for that assessment.  The missing item will be 
imputed as the average of the non-missing items from the same MDS-UPDRS 
assessment.  Imputation for Part I, Part II, Part III, or Part IV scores will use the non-
missing items within the particular part, but the imputation for the total score of 
Parts I - III will use the non-missing items from all 59 items across the 3 parts.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
23
PDSS-2
There is no imputation of missing responses for the PDSS-2.  If any item score is missing, 
the total score and the corresponding domain score will not be calculated.
PDQ-39
The PDQ-39 summary index will be calculated as long as no more than 15% (i.e., 5) of 
the answers are missing for that assessment.  It will be imputed as the average of the non-
missing items from the same PDQ-39 assessment.  The domain score will only be 
calculated if all the questions are answered.
EQ-5D-5L
The EQ-5D-5L summary index will only be calculated if answers are provided for all 
5 individual questions.  The EQ-5D-5L VAS is a single value collected and there is no 
imputation if the VAS value is missing.
8.2.2
Handling of Intercurrent Events and Missing Visit Values in 
Efficacy Endpoints
The probability of having missed visits and missing data due to COVID-19 infection or 
logistical restrictions can be reasonably assumed to be unrelated to unobserved values.  
For the purpose of the statistical analysis, it is reasonable to assume that these missing 
data are missing at random (MAR) and the statistical models that require MAR 
assumptions are appropriate.
Intercurrent events and missing data will be handled using the following methods for 
efficacy analyses:
●
The primary approach for handling missing data for all efficacy endpoints will 
use Mixed-Effect Model Repeat Measurement (MMRM).  All observations 
during the period from Day 1 to 1 day after the last dose of double-blind study 
drug (regardless of rescue medication use during this time period) will be 
included.  Rescue medication is defined in Section 6.0.  The repeated measures 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
24
analysis will be conducted using a mixed model including observed 
measurements at all visits.  The mixed model includes the categorical fixed 
effects of treatment, country and visit, treatment-by-visit and treatment-by-
baseline interactions, and the continuous fixed covariate of baseline 
measurement.  An unstructured variance covariance matrix will be used.  The 
compound symmetry variance covariance matrix will be used if the model does 
not converge with the unstructured matrix.  The "hypothetical" strategy will be 
used to handle the intercurrent event of discontinuation of study drug in the 
sense that all data collected more than 1 day after the last dose of blinded study 
drug will not be used in analyses.  In addition, the "treatment policy" strategy 
will be used to handle the intercurrent event of rescue medication use in the 
sense that collected data (from Day 1 to 1 day after the last dose of double-
blind study drug) will be used regardless of rescue medication use.  Parameter 
estimation is based on the assumption of data being MAR and using the method 
of restrictive maximum likelihood (REML).  MMRM will be the primary 
approach in the analysis of continuous variables in the Double-Blind Treatment 
Period.
●
The "Jump-to-reference" (J2R) missing not at random (MNAR) analytic 
approach (Liu and Pang 20162) will be used as Sensitivity Analysis  #1 for the 
primary efficacy endpoint and other "On" times as well as "Off" time derived 
from the PD Diary.  All observations during the period from Day 1 to 1 day 
after the last dose of double-blind study drug (regardless of rescue medication 
use during this time period) will be included.
○
In this approach missing data in the active control arm will be assumed to 
be MAR.
○
Non-monotonic missing data in the investigational group will also be 
assumed to be MAR.
○
For subjects in the investigational group with monotonic missing values 
due to reasons other than COVID-19 infection or COVID-19 logistical 
restrictions, the missing values will be assumed to be MNAR and have a 
profile for visits after discontinuation of blinded study drug that equals the 
profile of the active control group.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
25
○
The J2R analytic approach will be implemented to estimate the mean 
treatment group difference and standard error using MMRM estimates 
from the primary analysis model, observed proportions of missing data 
pattern in the investigational group due to reasons other than COVID-19, 
and the variance covariance matrix of the estimates from the MMRM (Liu 
and Pang 20162).
●
The last available value approach will be used as Sensitivity Analysis #2 for the 
primary efficacy endpoint and other "On" times as well as "Off" time derived 
from the PD Diary.  Missing Week 12 data will be imputed based on the 
subject's last available value (regardless of rescue medication use while the 
subject is on blinded study drug) in estimating the change from Baseline to 
Week 12.  An analysis of covariance (ANCOVA) model with the categorical 
fixed effects of treatment and country, and baseline score as a covariate will be 
used for treatment group comparison.
8.3
Primary Efficacy Endpoint and Analyses
8.3.1
Primary Efficacy Endpoint
The primary efficacy endpoint is the change from Baseline to Week 12 of the Double-
Blind Treatment Period in average daily normalized "On" time without troublesome 
dyskinesia (hours) ("On" time without dyskinesia plus "On" time with non-troublesome 
dyskinesia).
The estimand corresponding to the primary objective for the study is: the treatment group 
difference in "On" time without troublesome dyskinesia change from Baseline to Week 12 
between investigational and active control groups without premature discontinuation of 
double-blind study drug but regardless of rescue medication use in the FAS population.
8.3.2
Primary Efficacy Analysis
The primary analysis will use MMRM and include data on change from Baseline to each 
post-baseline visit of the Double-Blind Treatment Period in average daily normalized 
"On" time without troublesome dyskinesia obtained from the PD Diary.  The mixed 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
26
model includes the categorical fixed effects of treatment, country and visit, treatment-by-
visit and treatment-by-baseline interactions, and the continuous fixed covariate of baseline 
measurement.  Although randomization is stratified by study site, the MMRM model will 
not include the "site" effect due to the large number of sites planned compared to the 
number of subjects that will be randomized in the study.  If the final number of sites that 
randomized at least 1 subject is less than or equal to 30, the "site" effect may be added to 
the model.  The primary approach for handling intercurrent events and missing data will 
be based on the MMRM method as specified in Section 8.2.2.
An unstructured variance covariance matrix will be used.  Due to the short half-life (~1.5 
hours) of ABBV-951, the compound symmetry variance covariance matrix will be used if 
the model does not converge with unstructured matrix. Parameter estimation is based on 
the REML method.  The primary comparison will be the contrast on change from Baseline 
between the investigational and active control groups at Week 12.
Change from Baseline in average daily normalized "On" time without troublesome 
dyskinesia conducted on MMRM will be displayed by investigational group and active 
control group in a figure.
The proportion of subjects who met average daily normalized 'On' time without 
troublesome dyskinesia responder criteria at Week 12 will be summarized by 
investigational group and active control group at the thresholds from 0% to 100% with 
10% as an increment.  The P-value for test difference in the distribution between the 2 
groups will be provided by conducting the Monte Carlo exact Kolmogorov-Smirnov test.  
The percentage of subjects who achieved at least one certain percent reduction in average 
daily normalized "On" time without troublesome dyskinesia at endpoint will be displayed 
by investigational group and active control group in a figure.  The same analysis will also 
be conducted for average daily normalized 'Off' time.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
27
8.3.3
Additional Analyses of the Primary Efficacy Endpoints
Two sensitivity analyses will be conducted on the efficacy endpoints to account for 
missing data.
●
Sensitivity analysis #1:  A "jump-to-reference" analytic approach to account for 
missing data due to subjects who prematurely discontinue blinded study drug 
during the Double-Blind Treatment Period will be implemented as described in 
Section 8.2.2.
●
Sensitivity analysis #2:  The change from Baseline to the last available value in 
average daily normalized "On" time without troublesome dyskinesia and other 
"On" times as well as "Off" time derived from the PD Diary will be analyzed 
using an ANCOVA model with the categorical fixed effects of treatment and 
country, and baseline score as a covariate.  If the final number of sites that 
randomized at least 1 subject is less than or equal to 30, the "site" effect may be 
added to the model.  Missing Week 12 data will be handled using the last 
available value approach as specified in Section 8.2.2.
A summary of the primary and 2 sensitivity analyses of the primary efficacy endpoint is 
presented in Table 1.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
28
Table 1.
Summary of Primary and Sensitivity Analysis for the Primary 
Efficacy Endpoint of Change from Baseline to Week 12 in Average 
Daily Normalized "On" Time Without Troublesome Dyskinesia
and other "On" times as well as "Off" time derived from the PD 
Diary
Analysis
Dependent 
Variable
Data Included
Analysis Method
Primary 
Analysis
Change from 
baseline to post-
baseline visits 
through Week 12 
During the period 
from Day 1 to 
1 day after the last 
dose of double-
blind study drug, 
regardless of 
rescue medication 
use during this 
time period.
MMRM with categorical fixed effects of 
treatment, country and visit, treatment-by-visit 
and treatment-by-baseline interactions, and the 
continuous fixed covariate of baseline 
measurement.  Missing data will be handled 
using MMRM as specified in Section 8.2.2.
Sensitivity 
Analysis #1
Jump-to-Reference will be used to handle 
missing data in the investigational arm.  The 
details for this approach are described in 
Section 8.2.2.
Sensitivity 
Analysis #2
Change from 
baseline to the 
Week 12 visit 
ANCOVA model with the categorical fixed 
effects of treatment and country, and baseline 
score as a covariate.  Missing Week 12 data 
will be imputed using last available value.
8.4
Secondary Efficacy Analyses
8.4.1
Key Secondary and Other Secondary Efficacy Analyses
Key secondary efficacy endpoints and other secondary endpoints included in FWER 
control are described in Section 3.2.
Change from Baseline to Week 12 in average daily normalized "Off" time, MDS-UPDRS 
Part II score, average daily normalized "On" time without dyskinesia, and PKG variables 
will be analyzed using the same MMRM model as the primary efficacy analysis.
Change from Baseline to Final Visit in the PDSS-2 total score, PDQ-39 summary index, 
and EQ-5D-5L summary index will be analyzed using an ANCOVA model with 
categorical fixed effects of treatment and country, and baseline score as a covariate.  If the 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
29
final number of sites that randomized at least 1 subject is less than or equal to 30, the 
"site" effect may be added to the model.
The percent of subjects in each category of first morning status upon awakening ("Off,"
"On" without dyskinesia, "On" with non-troublesome dyskinesia, and "On" with 
troublesome dyskinesia) will be presented by visit and treatment group.  The number of 
hours from the last dose of blinded oral study drug to the first morning non-sleep status 
will be summarized.  
The first morning status upon awakening ("Off" or not "Off") on the last valid PD Diary 
day at each post-baseline visit will be analyzed using a generalized linear mixed model 
(GLMM) with a logit link function to compare the probability of having morning akinesia 
between the treatment groups.  The model will include fixed, categorical effects of 
treatment, country, visit, treatment-by-visit interaction, and baseline first morning status 
upon awakening.  An unstructured variance covariance matrix will be used.  The 
compound symmetry variance covariance matrix will be used if the model does not 
converge with unstructured matrix.  The odds ratio for treatment comparison at Week 12 
and their associated 95% CIs will be estimated from the GLMM.
Change from Baseline in average daily normalized "Off" time conducted on MMRM will 
be displayed by investigational group and active control group in a figure.
8.4.2
Other Efficacy Analyses
Other supportive efficacy variables are described in Section 3.3.  Variables derived from 
the PD diary, MDS-UPDRS, and PKG wearable device will be analyzed using the same 
MMRM model as the primary efficacy analysis.  Variables derived from the PDSS-2, 
PDQ-39, and EQ-5D-5L will be analyzed with the same ANCOVA model described in 
Section 8.4.1.
Distribution of time spent in different motor symptoms based on PD Diary data will be 
displayed in pie charts for the Baseline Visit and the Week 12 Visit.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
30
8.5
Efficacy Analyses During the Oral CD/LD Stabilization 
Period
Additional efficacy variables for the Oral CD/LD Stabilization Period are described in 
Section 3.5.  These variables will be summarized by investigational and active control 
groups and for all subjects in the FAS.  No statistical testing will be performed.
8.6
Efficacy Subgroup Analyses
Subgroup analyses of change from Baseline to Final Visit of the Double-Blind Treatment 
Period in average daily normalized "On" and "Off" times will be conducted for the 
following subgroups:
●
Age category (< 65 years or ≥ 65 years)
●
Sex (male or female)
●
Race (white or other)
●
Country (US or Australia)
●
Duration of PD (time since diagnosis to randomization) (< 10 years or ≥ 10 
years)
●
Concomitant dopamine agonist use (yes or no)
●
Dose category (low or high levodopa dose).  Each subject will be categorized to 
a dose subgroup based on the modal total daily dose over the treatment period.  
The calculation of modal total daily dose is defined in Section 7.4.3.
A subgroup analysis will be conducted on dose subgroup for the key secondary and other 
secondary endpoints described in Section 3.2 except for the variables that were derived 
from the PD diaries, which were analyzed by all subgroups described in the above 
paragraph.
A subgroup analysis may not be conducted if one stratum of the subgroup variable 
comprises of < 20% of the FAS Analysis Set.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
31
Subgroup analyses will be performed on the FAS using an ANCOVA model with the 
terms of treatment, subgroup variable, the treatment-by-subgroup variable interaction, and 
Baseline as a covariate.  The hypothesis that consistent response to treatment across strata 
of a subgroup variable will be tested at the significance level of 0.100 by examining the 
P value of the treatment-by-subgroup interaction term in the ANCOVA model specified 
above.  The statistical comparison of the investigational and active control groups within 
each subgroup stratum will be performed when the statistical significance of the 
treatment-by-subgroup interaction term is achieved at 0.100 level.
9.0
Safety Analyses
9.1
General Considerations
Safety data will be summarized for the Double-Blind Treatment Period using the Safety 
Analysis Set unless otherwise specified.  Safety summaries during the Double-Blind 
Treatment Period will be presented by dose subgroup (low dose or high dose) within each 
treatment group unless otherwise specified.  For safety analyses of the Double-Blind 
Treatment Period, subjects are assigned to a treatment group based on the treatment 
actually received, regardless of the treatment randomized.
Baseline for all safety measures will be defined as the last non-missing observation that is 
before the day of randomization, with the exception of vital sign variables, which will be 
the average of observations if multiple measurements are obtained on the same day.
For continuous safety outcomes, the change from Baseline will be analyzed in a 
descriptive manner by visit for each dose category subgroup and overall subjects.  For 
categorical safety outcomes, the number and percentage of each category will be 
summarized by visit for each dose category subgroup and overall subjects.  Hypothesis 
testing will not be performed.
To evaluate the time dependency of effects, select analyses will be prepared for treatment 
intervals:  Optimization Phase, Maintenance Phase, and persistent from Optimization 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
32
Phase to Maintenance Phase for at least 7 days into the Maintenance Phase, which begin 
in the Optimization Phase and continue in the Maintenance Phase.
9.2
Adverse Events
AEs will be summarized and presented using primary MedDRA SOCs and PTs according 
to the version of the MedDRA used for the study at the time of database lock.  The actual 
version of the MedDRA used will be specified in the AE tables and in the clinical study 
report.  Specific AEs will be counted only once for each subject for calculating 
percentages, unless stated otherwise.  In addition, if the same AE occurs multiple times 
within a subject, the highest severity and level of relationship to study drug will be 
reported.  Subjects for whom more than one AE for a given PT was reported will be 
counted only once for that term.  Subjects for whom more than one AE within an SOC 
was reported will be counted only once for the SOC total.  Subjects for whom more than 
one AE was reported will be counted only once in the overall AE total.  For summaries by 
SOC and PT, the SOCs will be presented in alphabetical order and the PTs will be 
presented in alphabetical order within each SOC.
9.2.1
Treatment-Emergent Adverse Events
Treatment emergent AEs (TEAEs) for the Oral CD/LD Stabilization Period will be 
defined as all events that begin or worsen on or after first dose of open-label CD/LD IR 
tables during the Oral CD/LD Stabilization Period and prior to first dose of blinded study 
drug during the Double-Blind Treatment Period.  TEAEs for the Double-Blind Treatment 
Period will be defined as all events that begin or worsen on or after first dose of study 
drug during the Double-Blind Treatment Period and within 30 days after the last dose of 
double-blinded study drug.  AEs with onset on the first day of blinded study drug will be 
considered treatment-emergent for the Double-Blind Treatment Period.  All TEAEs will 
be summarized by treatment intervals and entire Double-Blind Treatment Period, by 
primary MedDRA SOC and PT.  The SOCs will be presented in alphabetical order, and 
the PTs will be presented in alphabetical order within each SOC.  The number of subjects 
who experienced the same TEAE recurrently during the Optimization Phase, the 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
33
Maintenance Phase, and the entire Double-Blind Treatment Period will be presented by 
frequency counts: 1 time, 2-4 times, 5-10 times, and >10 times.
9.2.2
Adverse Event Overview
An overview of AEs during the Oral CD/LD Stabilization Period will be presented for the 
Oral CD/LD Analysis Set, consisting of the number and percentage of subjects 
experiencing at least one event for each of the following AE categories:
●
Any TEAE
●
Any TEAE are considered associated with study drug
●
Any severe TEAE
●
Any serious TEAE
●
Any TEAE considered associated with COVID-19
●
Any TEAE leading to discontinuation of study drug
●
Any TEAE leading to death
●
AESI:  Polyneuropathy
●
AESI:  Weight loss
●
AESI:  Hallucinations/psychosis
●
AESI:  Somnolence
●
AESI: Falls and associated injuries
●
All deaths
●
Death related to COVID-19
An overview of AEs during the Double-Blind Treatment Period will be presented for the 
Safety Analysis Set, consisting of the number and percentage of subjects experiencing at 
least one event for each of the following AE categories:
●
Any TEAE
●
Any TEAE are considered associated with study drug
●
Any severe TEAE
●
Any serious TEAE


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
34
●
Any TEAE associated with any product complaint
●
Any TEAE considered associated with product complaint:  ABBV-951 or 
Placebo solution
●
Any TEAE considered associated with product complaint:  CD/LD IR or 
Placebo capsules
●
Any TEAE considered associated with product complaint:  Open label CD/LD 
IR tablets
●
Any TEAE considered associated with product complaint:  Infusion Pump 
(Phillips-Medisize - Parkinson's Disease subcutaneous pump [PM-PDSC 
pump])
●
Any TEAE considered associated with product complaint:  Vial Adapter
●
Any TEAE considered associated with product complaint:  Syringes
●
Any TEAE considered associated with product complaint:  Neria Guard 
Infusion Set 6 mm Cannula
●
Any TEAE considered associated with product complaint:  Neria Guard 
Infusion Set 9 mm Cannula
●
Any TEAE considered associated with product complaint:  PKG Wearable 
Device
●
Any TEAE considered associated with COVID-19
●
Any serious TEAE considered associated with the PM-PDSC infusion pump
●
Any TEAE leading to discontinuation of study drug
●
Any TEAE leading to death
●
AESI:  Infusion Site Related Non-Infection Reactions
●
AESI:  Infusion Site Related Infections 
●
AESI:  Polyneuropathy
●
AESI:  Weight loss
●
AESI:  Hallucinations/psychosis
●
AESI:  Somnolence
●
AESI: Falls and associated injuries
●
All deaths


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
35
●
Death related to COVID-19
9.2.3
Treatment-Emergent Adverse Events by SOC and/or PT
TEAEs during the Double-Blind Treatment Period will be summarized by SOC and PT; 
by maximum relationship to study drug as assessed by the investigator (i.e., reasonable 
possibility or no reasonable possibility) and SOC and PT; and by maximum severity and 
SOC and PT for the Safety Analysis Set.  Specific AEs will be counted once for each 
subject for calculating percentages, unless stated otherwise.  In addition, if the same AE 
occurs multiple times within a subject, the highest severity and level of relationship to the 
study drug will be reported.
TEAE reported in ≥2% of subjects in the ABBV-951 group and greater than the Oral 
CD/LD group will be summarized. 
In addition, TEAEs will be summarized by PT and sorted by decreasing frequency for the 
ABBV-951 group. The number and percentage of subjects with TEAEs during the 
Double-Blind Treatment Period associated with product complaint, loading dose, and 
rescue medication will be presented by SOC and PT for both the ABBV-951 group and 
oral CD/LD group.
TEAEs during the Oral CD/LD Stabilization Period will be summarized by SOC and PT 
for the Oral CD/LD Analysis Set.
9.2.4
Adverse Event by Maximum Severity
The number and percentage of subjects who experienced one or more TEAEs will also be 
summarized by maximum severity category (mild, moderate, severe, or unknown) and 
primary SOC and PT for the entire study.  Subjects for whom more than one TEAE for a 
given PT was reported will be counted only once for that term in the most severe category 
reported.  If a subject has an AE with unknown severity, then the subject will be counted 
in the severity category of "unknown," even if the subject has another occurrence of the 
same event with a severity present.  The only exception is if the subject has another 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
36
occurrence of the same AE with the most extreme severity – "severe."  In this case, the 
subject will be counted under the "severe" category.
9.2.5
Adverse Event by Relationship to Study Drug
The number and percentage of subjects who experienced one or more TEAEs will also be 
summarized by maximum relationship category (reasonable possibility, no reasonable 
possibility, or unknown), as assessed by the investigator, and primary SOC and PT for the 
entire study.  Subjects for whom more than one TEAE for a given PT was reported will be 
counted only once for that term in the most related category reported.  If a subject has an 
AE with unknown relationship, then the subject will be counted in the relationship 
category of "unknown," even if the subject has another occurrence of the same event with 
a relationship present.  The only exception is if the subject has another occurrence of the 
same AE with a relationship assessment of "reasonable possibility."  In this case, the 
subject will be counted under the "reasonable possibility" category.
9.2.6
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure
Exposure-adjusted AEs per 100 patient-years will be provided, where AEs per 
100 patient-years of exposure are defined as the number of AEs divided by the total 
exposure in 100 patient-years.
9.2.7
Adverse Events of Special Interest
Adverse events of special interest during the Double-Blind Treatment Period in each of 
the following categories will be defined based on the search strategy defined in 
Appendix B:
●
Infusion site related non-infection reactions
●
Infusion site related infections 
●
Polyneuropathy
●
Weight loss
●
Hallucinations/psychosis


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
37
●
Somnolence
●
Falls and associated injuries
An overview of AESIs will be summarized. The number and percentage, difference of 
percentage between the active control group and investigational group and its 95% CI of 
each AESI category will be summarized by treatment intervals and entire Double-Blind 
Treatment Period by descending PT.  AESI that develop into an SAE or that led to study 
drug discontinuation will be summarized by treatment intervals and entire Double-Blind 
Treatment Period by descending PT.
In addition, for each AESI, the time of first onset, number of events and duration of events 
will be summarized given sufficient data. 
9.2.8
Adverse Event by Relationship to Product Quality 
Complaints
The number and percentage of subjects experiencing one or more TEAEs that are 
associated with Product Quality Complaints will also be summarized by SOC and PT for 
the products listed below:
●
ABBV-951 or placebo solution
●
CD/LD IR or placebo capsules
●
Open label CD/LD IR tablets
●
PM-PDSC infusion pump
●
Vial adapter
●
Syringes
●
Neria Guard Infusion Set 6 mm Cannula
●
Neria Guard Infusion Set 9 mm Cannula
●
PKG wearable device  


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
38
9.2.9
Adverse Event Leading to Study Drug Discontinuation, 
Interruption, and Dose Reduction
The number and percentage of subjects who experienced one or more TEAEs that led to 
study drug discontinuation, interruption, and dose reduction will also be summarized by 
primary SOC and PT, respectively.
AEs during the Double-Blind Treatment Period that led to study drug discontinuation will 
be summarized by treatment intervals and entire Double-Blind Treatment Period by SOC 
and PT.  All death subjects will be listed for both the Oral CD/LD Analysis Set and Safety 
Analysis Set.
9.2.10
Adverse Event Associated with Rescue Medication
The number and percentage of subjects who experienced one or more TEAEs associated 
with rescue medication will also be summarized by primary SOC and PT, respectively.
9.2.11
Serious Adverse Events
The number and percentage of subjects who experienced one or more SAEs related to the 
PM-PDSC infusion pump and Neria Guard infusion set will be summarized by primary 
SOC and PT for the entire study and in listing format.  All SAEs will be summarized by 
treatment intervals and entire Double-Blind Treatment Period by SOC and PT.
9.2.12
TEAE identified by Abuse Liability Company MedDRA Query
The number and percentage of subjects with TEAEs, with TESAEs, and with TEAEs 
leading to study drug discontinuation during the Double-Blind Treatment Period 
identified by the Abuse Liability Company MedDRA Query (CMQ) will be summarized 
in descending frequency for ABBV-951 group by PT and will be presented in listing 
format as well. 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
39
9.2.13
COVID-19 related Adverse Events
Subjects with TEAEs related to COVID-19 will be summarized by treatment intervals and 
entire Double-Blind Treatment Period by PT.  Subjects' COVID-19 status, signs, and 
symptoms for all screened subjects will be summarized and listed as well. 
9.2.14
Listings of Adverse Events
The following additional summaries of AEs will be prepared.
●
Listing of all deaths for all subjects screened
●
Listing of all serious TEAEs
●
Listing of all TEAEs that led to discontinuation of study treatment
●
Listing of all AESIs (as defined in Section 9.2.7)
●
Listing of all TEAEs by the Abuse Liability CMQ
●
Listing of all TEAEs related to COVID-19
●
Listing of subjects' COVID-19 status, signs, and symptoms
9.3
Safety Subgroup Analyses
Any TEAE, any SAE, any AE that led to study drug discontinuation, any AESI, any AESI 
that developed to an SAE, and any AESI that led to study drug discontinuation will be 
summarized for dose category (low or high levodopa dose) within each treatment group 
and within each of the following subgroup variables, and treatment intervals and entire 
Double-Blind Treatment Period by SOC and PT.
●
Age category (< 65 years or ≥ 65 years)
●
Sex (male or female)
●
Race (white or other)
●
Country (US or Australia)
●
Duration of PD (time since diagnosis to screening) (< 10 years or ≥ 10 years)
●
BMI (< 25 or ≥ 25)
●
Concomitant dopamine agonist use (yes or no)


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
40
●
Dose category (low or high levodopa dose) defined by the modal total daily 
dose over the treatment period.  The calculation of modal total daily dose is 
defined in Section 7.4.3.  All safety variables will be summarized by dose 
subgroup within each treatment group unless otherwise specified.
Change from Baseline analyses and safety parameter abnormalities that meet Potentially 
Clinically Significant (PCS) criteria analyses of laboratory parameters, vital sign, and 
ECG parameters will also be analyzed by subgroups and by dose category.  Details are 
described in following sections.
9.4
Analysis of Laboratory Data
Data collected from central and local laboratories, including additional laboratory testing 
due to an SAE, will be used in all analyses, except for Baseline where SAE-related 
laboratory assessments on or before the first dose of study drug will be excluded.  The 
clinical laboratory tests defined in the protocol operations manual will be summarized.
Mean change from Baseline to the final value of the Double-Blind Treatment Period will 
be summarized for chemistry, hematology, urinalysis, and special laboratory variables, 
with the number of observations, baseline mean, and visit mean by subgroup variables 
listed in Section 9.3.  The change from baseline mean, standard error, and 95% confidence 
interval will be presented for the mean change from Baseline within each treatment group 
and difference between treatment groups (investigational group vs. active control group).
Changes in laboratory parameters from Baseline to the final value will be tabulated using 
shift tables by Common Terminology Criteria for Adverse Events (CTCAE) grades if 
available, and categorized as low, normal, or high based on the normal ranges of the 
laboratory that performed the assay.
Laboratory abnormalities will be evaluated based on sponsor PCS criteria (Appendix C).  
For each laboratory sponsor PCS criterion (includes the Hy's Law lab criteria), the number 
and percentage of subjects who have a laboratory value that meets the criteria and is more 
extreme than their baseline value will be summarized by the subgroup variables listed in 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
41
Section 9.3.  Listings will be provided to summarize subject-level laboratory data for 
subjects who meet sponsor PCS criteria by subgroups.
Laboratory abnormalities will be evaluated based on FDA PCS criteria (Appendix C).  
For each laboratory FDA PCS criterion, the number and percentage of subjects who have 
a laboratory value meeting the criteria and is more extreme than their baseline value will 
be summarized by subgroup variables listed in Section 9.3.  Listings will be provided to 
summarize subject-level laboratory data for subjects meeting FDA PCS criteria by 
subgroups.
Subjects who meet the criteria for liver-related laboratory elevations will be summarized 
and a listing will be provided for subjects with ALT or AST ≥ 3 × ULN.
●
ALT > 3 × ULN, > 5 × ULN, > 10 × ULN, > 20 × ULN 
●
AST > 3 × ULN, > 5 × ULN, > 10 × ULN, > 20 × ULN
●
TBL > 1.5 × ULN, > 2 × ULN 
●
ALT and/or AST > 3 × ULN and TBL > 1.5 × ULN 
●
ALT and/or AST > 3 × ULN and TBL > 2 × ULN 
●
ALT > 3 × ULN and TBL > 1.5 × ULN 
●
ALT > 3 × ULN and TBL > 2 × ULN 
●
Alkaline phosphatase > 1.5 × ULN 
9.5
Analysis of Vital Signs
Vital sign measurements including blood pressure both supine, standing, orthostatic 
systolic blood pressure (SBP) changes and orthostatic diastolic blood pressure (DBP) 
change, pulse rate both supine, standing and orthostatic pulse rate changes, and body 
temperature will be summarized.  Orthostatic changes are defined as change in values 
from supine to standing (standing value minus supine value) position in SBP, DBP, and 
pulse rate.
Weight variables are weight and BMI.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
42
Each vital sign variable will be summarized for all time points (starting with Baseline) 
with the number of non-missing observations, mean and standard deviation, median, 
minimum, and maximum.  Mean change from Baseline to each applicable post-baseline 
visit of the Double-Blind Treatment Period will be summarized by subgroup variables 
listed in Section 9.3 for each vital sign variable and weight, with the number of 
observations, baseline mean, and visit mean.
An MMRM analysis will be conducted for blood pressure and pulse variables by position 
(supine and standing) and will include data on change from Baseline to each post-baseline 
visit of the Double-Blind Treatment Period.  The mixed model includes the categorical 
fixed effects of treatment and visit, treatment-by-visit and treatment-by-baseline 
interactions, and the continuous fixed covariate of baseline measurement.  The change 
from Baseline mean, standard error, and 95% confidence interval will be presented for the 
mean change from Baseline within each treatment group and difference between treatment 
groups (investigational group vs. active control group).
Vital sign values and change from Baseline by visit will be summarized with dose 
category and with the number of non-missing observations, mean and standard deviation, 
median, minimum and maximum per FDA request for blood pressure and pulse variables.
Vital sign variables will be evaluated based on sponsor PCS criteria (Appendix C).  For 
each vital sign PCS criterion, the number and percentage of subjects who have a vital sign 
value that meets the criteria and is more extreme than their baseline value will be 
summarized for the Optimization Phase, the Maintenance Period, any time in the Double-
Blind Treatment Period and at each planned visit and the final visit.  The summary will 
also be generated by the subgroup variables listed in Section 9.3.  Listings will be 
provided to summarize subject-level vital sign data for subjects who meet PCS criteria by 
subgroups.
Vital sign variables will be evaluated based on PCS criteria recommended by FDA.  For 
each vital sign FDA PCS criterion, the number and percentage of subjects who have a 
vital sign value that meets the criteria and is more extreme than their baseline value will 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
43
be summarized by subgroup variables listed in Section 9.3.  Listings will be provided to 
summarize subject-level vital sign data for subjects who meet FDA PCS criteria by 
subgroups.  For all vital sign analyses described above, Baseline will be the average of the 
3 sets of values collected at V5.  
In addition, each vital sign variable will be summarized for Day 1 pre-dose, post-dose, 
and change from pre-dose to post-dose with the number of non-missing observations, 
mean and standard deviation, median, minimum, and maximum.  
9.6
Other Safety Analyses
9.6.1
Analysis of ECG Parameters
Electrocardiogram (ECG) variables are:  heart rate (HR), PR interval, QRS interval, 
uncorrected QT interval, and QT interval corrected for heart rate using the Fridericia's 
formula (QTcF).
Change from Baseline to each planned visit and to the minimum, maximum, and final 
value will be summarized in a descriptive manner for each ECG variable.
For each change from baseline analysis, the following summary statistics will be 
presented:  sample size, baseline mean, visit mean, and the mean, standard deviation, and 
median of the change from Baseline by subgroup variables listed in Section 9.3 and by 
dose category.  The baseline and visit means will be calculated for each visit for subjects 
who have both a baseline and visit value.
Criteria for PCS values have been predefined for selected ECG variables as outlined in 
Appendix C.  For each variable, a summary of the number and percentage of subjects who 
have at least one post-baseline observation that meets the PCS criteria and is more 
extreme than their baseline value will be provided for the Optimization Phase, the 
Maintenance Period, any time in the Double-Blind Treatment Period and at each planned 
visit and the final visit.  The summary will also be generated by the subgroup variables 
listed in Section 9.3.  A listing will also be prepared that will include, for each variable, all 


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
44
observations for each subject that met the PCS criteria for that variable at any time during 
the study by subgroups. 
9.6.2
Infusion Site Evaluation Scale
The number and percentage of subjects with each category for numeric and letter grade 
will be presented by treatment group and for both treatment groups combined at each 
planned visit during the Double-Blind Treatment Period.  The number and percentage of 
subjects with numeric grade equal to or higher than 5 or letter grade equal to or higher 
than D at any time during the Double-Blind Treatment Period will be presented by 
treatment group and for both treatment groups combined.
A listing will also be prepared that includes all subjects with numeric grade equal to or 
higher than 5 and letter grade equal to or higher than D at any time during the Double-
Blind Treatment Period.
9.6.3
Analysis of Questionnaire for Impulsive-Compulsive 
Disorders in PD-Rating Scale (QUIP-RS)
Change from Baseline to each applicable post-baseline visit of the Double-Blind 
Treatment Period will be summarized in a descriptive manner for the QUIP-RS total score 
and domain scores.
For each change from baseline analysis, the following summary statistics will be 
presented:  sample size, baseline mean, visit mean, and the summary statistics (i.e., mean, 
SD, and median) of the change from Baseline.  Summary statistics for the change from 
Baseline will only be calculated for subjects who have both baseline and visit values.
In addition, a summary of the number and percentage of subjects with a score of at least 6 
on each of the subscales and any one or more of the subscales will be prepared. A listing 
of QUIP-RS scores will also be prepared for any subjects having a score of at least 6 on 
any of the subscales.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
45
9.6.4
Analysis of Columbia-Suicide Severity Rating Scale 
(C-SSRS)
Affirmative responses on the C-SSRS will be summarized for the initial screening and 
each subsequent visit by treatment group.
Each summary will include the number and percentage of subjects within each treatment 
group with one or more affirmative responses to each of the 5 suicidal ideation questions, 
each of the 6 suicidal behavior questions, any of the 5 suicidal ideation questions, any of 
the 6 suicidal behavior questions, any suicidal ideation or behavior question, and the non-
suicidal self-injurious behavior question.
A listing will also be prepared that includes all subjects with 1 or more affirmative 
responses.
10.0
Interim Analyses
No interim analysis on efficacy or safety data is planned for this study.
11.0
Overall Type I Error Control
A multiple testing procedure will be used to provide strong control of the Type I error rate 
at alpha = 0.05 (2-sided) across analyses comparing the investigational group to the active 
control group with respect to the primary efficacy endpoint and ranked secondary 
endpoints.  Specifically, testing will use a sequence of hypothesis testing for the primary 
endpoint followed by the ranked secondary endpoints.  If the primary endpoint achieves 
statistical significance with a P-value ≤ 0.05, continued testing will proceed in the 
following order:
●
Key secondary endpoints:
○
Change from Baseline to Week 12 in hours of average daily normalized 
"Off" time 
○
Change from Baseline to Week 12 in MDS-UPDRS Part II score
○
Presence of morning akinesia at Week 12


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
46
●
Other secondary endpoints included in FWER control:
○
Change from Baseline to Week 12 in hours of average daily normalized  
"On" time without dyskinesia 
○
Change from Baseline to Final Visit in PDSS-2 total score
○
Change from Baseline to Final Visit in PDQ-39 summary index
○
Change from Baseline to Final Visit in EQ-5D-5L summary index
○
Change from Baseline to Week 12 in median bradykinesia score (BK50) as 
assessed by the Parkinson's KinetiGraph™/Personal KinetiGraph™ (PKG) 
wearable device
○
Change from Baseline to Week 12 in interquartile range of bradykinesia 
score (BK75-BK25) as assessed by the PKG wearable device
○
Change from Baseline to Week 12 in median dyskinesia score (DK50) as 
assessed by the PKG wearable device
○
Change from Baseline to Week 12 in interquartile range of dyskinesia 
score (DK75-DK25) as assessed by the PKG wearable device


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
47
12.0
Version History
Table 2.
SAP Version History Summary
Version
Date
Summary
1.0
12 August 2020
Original version
2.0
13 September 2021
1.
Made changes to the list and ranking of secondary endpoints 
included in Type I error control prior to database lock and 
unblinding of Study M15-736.  The changes to secondary 
endpoints are based on results from an interim analysis of open-
label Phase 3 Study M15-741 as follows (Section 3.2 and 
Section 11.0): 

Moved presence of morning akinesia at Week 12 from other 
secondary endpoints to a key secondary endpoint.

Added change from Baseline to Week 12 in hours of average 
daily normalized "On" time without dyskinesia to the list of 
other secondary endpoints included in Type I error control.

Moved PDSS-2 total score up in the list of other secondary 
endpoints included in Type I error control so that it is ranked 
before the PDQ-39 summary index and EQ-5D-5L summary 
index.
2.
Change from Screening to Baseline of data derived from PD 
Diary and PKG wearable device will be analyzed on Full analysis 
set instead of Oral CD/LD analysis set to assign subjects to high 
dose or low dose in analysis table which is evaluated by double-
blind study drug (Section 4.0). 
3.
Updated criteria regarding how to assign subjects who receive 
both placebo or both active treatments to a treatment group in 
analyses (Section 4.0).
4.
Compliance will be assessed based on valid dosing diary days 
rather than all dosing diary days.  This is because unlike all 
dosing information being required on 3 days prior to certain visits, 
all rescue medication use during the Double-Blind Treatment 
Period is required to be recorded.  Therefore, blinded study drug 
information is not required on some dosing diary days.  
Compliance definition is revised such that only valid dosing diary 
days will be used (Section 6.0).
5.
Baseline MDS-UPDRS Part I-IV scores is removed from PD 
history summary because it will be included in Baseline efficacy 
analysis (Section 7.2).
6.
Deleted APD tool as the data is not collected in this study 
(Section 7.2)


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
48
Table 2.
SAP Version History Summary (Continued)
Version
Date
Summary
7.
Changed 'Titration' to 'Optimization' to be consistent with 
protocol term (Section 7.4.2).
8.
Changed definition of Baseline of PD Diary variables from "… 
before the day of randomization" to "… before the day of 
initiation of double-blinded study drug" to be consistent with 
analysis criteria (Section 8.1).
9.
Clarified that responder analysis of both average daily normalized 
"On" time without troublesome dyskinesia and "Off" time will be 
conducted (Section 8.3.2).  
10. Updated that all "On" times and "Off" time from PD Diary will be 
conducted for subgroup analyses (Section 8.6).
11. Clarified that how AEs will be summarized (Section 9.2)
12. Added analysis of AEs overview during Oral CD/LD 
Stabilization Period (Section 9.2.2).
13. Added "PM-PDSC" to infusion pump name (Section 9.2.2).
14. Changed "investigational group" to "ABBV-951 group" and 
changed "active-control group" to "Oral CD/LD group"
(Section 9.2.3).
15. Added "Neria Guard infusion set" in SAE related summary 
analyses (Section 9.2.11).
16. Added "TEAE identified by Abuse Liability Company MedDRA 
Query" analysis (Section 9.2.12).
17. Added detailed description lab variables that will be analyzed 
(Section 9.4).
18. Added "more extreme than their baseline value" condition to lab 
and vital sign PCS criteria definition (Section 9.4 and 
Section 9.5). 
19. Added analysis of subjects meeting criteria for liver-related 
laboratory elevations (Section 9.4). 
20. Added analysis of infusion site evaluation scale (Section 9.6.2).
21. Added other analysis and listing of QUIP-RS (Section 9.6.3).
22. Updated the AESI definition and search criteria in Appendix B.
23. Updated the PCS criteria for Lab, VS, and ECG in Appendix C.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
49
Table 2.
SAP Version History Summary (Continued)
Version
Date
Summary
3.0
19 October 2021
1.
Added inclusion criterion regarding hours of "Off" time at 
Screening and Randomization (Section 2.1).
2.
Clarified how treatment group assignment will be done for Safety 
Analysis Set in the event a subject is dispensed wrong study drug 
kit from randomized (Section 4.0). 
3.
Added additional summary of PD medications at Screening and 
Baseline (Section 7.3).
4.
Added sensitivity analysis for "On" times and "Off" time in 
addition to the primary endpoint (Section 8.2.2).
5.
Added summary of number of hours from the last dose of blinded 
oral study drug to the first morning non-sleep status 
(Section 8.4.1)
6.
Added that lab shift tables will be produced by lab normal range 
in additional to CTCAE criteria (Section 9.4).
7.
Revise the calculation of orthostatic vital sign as standing value 
minus supine value (Section 9.5 and Appendix C-4).
8.
Clarified that vital sign PCS summaries will be done for the 
Optimization Phase, the Maintenance Period, any time in the 
Double-Blind Treatment Period and at the final visit (Section 9.5).
9.
Clarified that ECG PCS summaries will be done for the 
Optimization Phase, the Maintenance Period, any time in the 
Double-Blind Treatment Period and at the final visit 
(Section 9.6.1).
13.0
References
1.
Tomlinson CL, Stowe R, Patel S, et al.  Systematic review of levodopa dose 
equivalency reporting in Parkinson's disease.  Mov Disord.  2010;25(15):2649-53.
2.
Liu GF, Pang L.  On analysis of longitudinal clinical trials with missing data using 
reference-based imputation.  J Biopharm Stat.  2016;26(5):924-36.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
50
Appendix A.
Protocol Deviations
The number and percentage of subjects who reported at least one of the following 
protocol deviation categories will be provided.
●
Subject randomized into the study even though s/he did not satisfy entry 
criteria.
●
Subject developed withdrawal criteria during the study and was not withdrawn.
●
Subject received wrong treatment or incorrect dose of study drug.
●
Subject took prohibited concomitant medication.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
51
Appendix B.
Definition of Adverse Events of Special Interest
Adverse Events of Special Interest (AESI) will be identified using the following search 
Adverse Event of Special 
Interest
Search Criteria
Infusion site related infections
Infusion Site Related Infections (AbbVie ABBV-951 product-specific) 
CMQ (code 10000089) 
Infusion site related non-
infection reactions
Infusion Site Related Non Infection Reactions (AbbVie ABBV-951 
product-specific) CMQ (code 10000178)
Hallucinations/Psychosis
Combined search:

Hallucinations CMQ (code 10000072)

Psychosis and Psychotic Disorders SMQ – narrow search 
(code 20000117).  
Polyneuropathy
Peripheral Neuropathy SMQ – broad and narrow search (code 
20000034)
Somnolence
Any of the following PTs:

Hypersomnia

Microsleep

Sleep attacks

Sleep disorder due to general medical condition, hypersomnia 
type

Somnolence

Sudden onset of sleep
Weight loss
Weight Loss CMQ (code 10000125)
Falls and associated injuries
Separate and combined searches:

Falls and Associated Injuries (AbbVie ABBV-951 product-
specific) CMQ (code 10000056)

Orthostatic Hypotension PT search including any of the 
following PTs: "blood pressure ambulatory decreased,"
"blood pressure orthostatic," "blood pressure orthostatic 
decreased," "dizziness," "dizziness postural," "orthostatic 
hypotension," "syncope"
CMQ = Company MedDRA Query; PT = MedDRA preferred term; SMQ = Standardized MedDRA Query


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
52
Appendix C.
Potentially Clinically Significant Criteria for Safety Endpoints
Appendix C-1.
Potentially Clinically Significant (PCS) Hematology Criteria
Variable
Sponsor Criteria
FDA Criteriaa
Very Low
Very High
Very Low
Very High
Activated partial 
thromboplastin 
time (aPTT) 
prolonged
-----
> ULN
-----
-----
Bands
≥14.0%
Bands, abs
≥ 1.4 × 109/L
Basophils
≥4.0%
Basophils, abs 
-----
-----
-----
≥ 0.25 × 109/L
Eosinophils
≥8.0%
Eosinophils, abs 
-----
-----
-----
≥ 0.7 × 109/L
Erythocytes (red 
blood cells)
-----
-----
≤ 3.0 × 1012/L
-----
Hematocrit
-----
-----
Female ≤ 65:  
≤30%
Female ≤ 65:  
≥54%
Female ≥ 66:  
≤28%
Female ≥ 66:  
≥52%
Male ≤ 65:  ≤ 34%
Male ≤ 65:  ≥ 60%
Male ≥ 66:  ≤ 32%
Male ≥ 66:  ≥ 58%
Hemoglobin
< 100 g/L
> 40 g/L above 
ULN
Female ≤ 65:  
≤99 g/L
Female ≤ 65:  
≥186 g/L
Female ≥ 66:  
≤94 g/L
Female ≥ 66:  
≥186 g/L
Male ≤ 65:  
≤110 g/L
Male ≤ 65:  
≥200 g/L
Male ≥ 66:  
≤107 g/L
Male ≥ 66:  
≥204 g/L
INR
-----
> ULN
-----
-----
Leukocytes (white 
blood cells)
< 2 × 109/L
>100 × 109/L
≤ 3.0 × 109/L
≥ 16.0 × 109/L
Lymphocytes
-----
-----
≤ 13.0%
≥ 54.0%
Lymphocytes, abs
< 0.5 × 109/L
> 20 × 109/L
≤ 0.8 × 109/L
≥ 4.0 × 109/L


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
53
Variable
Sponsor Criteria
FDA Criteriaa
Very Low
Very High
Very Low
Very High
Mean corpuscular 
volume (MCV)
-----
-----
≤ 65fL
≥ 115 fL
Mean corpuscular 
hemoglobin 
(MCH)
-----
-----
≤ 22 pg/cell
≥ 40 pg/cell
MCHC
-----
-----
≤ 264 gHb/L
≥ 426 gHb/L
Monocytes
-----
-----
≤ 2.6%
≥14.4%
Monocytes, abs
-----
-----
≤ 0.12 × 109/L
≥ 1.1 × 109/L
Neutrophils
-----
-----
≤ 30 %
≥90%
Neutrophils, abs
< 1 × 109/L
-----
≤ 1.7 × 109/L
≥ 10 × 109/L
Thrombocytes 
(platelets)
< 75 × 109/L
-----
≤ 100 × 109/L
≥ 550 × 109/L
a.
Criteria requested by FDA DNP for Levodopa Carbidopa Intestinal Gel (LCIG) NDA 203952.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
54
Appendix C-2.
Potentially Clinically Significant (PCS) Chemistry Criteria
Variable
Sponsor Criteria
FDA Criteriaa
Very Low
Very High
Very Low
Very High
Alanine 
aminotransferase 
(ALT, SGPT)
> 3 × ULN
-----
≥ 3 × ULN
Albumin
< 20 g/L
-----
≤ 65:  ≤ 30 g/L
≤ 65:  ≥ 60 g/L
-----
-----
≥ 66:  ≤ 27 g/L
≥ 66:  ≥ 53 g/L
Alkaline 
phosphatase
-----
> 2.5 × ULN
-----
≥ 3 × ULN
Aspartate 
aminotransferase 
(AST, SGOT)
-----
> 3 × ULN
-----
≥ 3 × ULN
Bicarbonate
-----
-----
≤ 18 mmol/L
≥ 34 mmol/L
Bilirubin (total)
-----
> 1.5 × ULN
-----
≥ 2 × ULN
Blood urea 
nitrogen (BUN)
-----
-----
-----
≤ 65:  
≥10.0 mmol/L
≥ 66:  
≥9.5 mmol/L
Calcium (total)
Corrected:  
< 1.75 mmol/L
Corrected:  
≥3.1 mmol/L
Corrected:
≤ 1.8 mmol/L
Corrected:
≥ 3.0 mmol/L
Chloride
-----
-----
≤ 87 mmol/L
≥ 116 mmol/L
Cholesterol (total)
-----
> 12.92 mmol/L
-----
≥6.5 mmol/L
Creatine 
phosphokinase 
(CPK)
-----
> 5 × ULN
-----
≥ 2 × ULN
Creatinine
-----
> 1.5 × ULN
-----
Female:  
≥122 mcmol/L
Male:  
≥132 mcmol/L
Gamma glutamyl-
transferase (GGT)
-----
> 2.5 × ULN
-----
≥ 3 × ULN
Glucose
< 2.2 mmol/L
> 13.9 mmol/L
≤ 3.0 mmol/L
≥ 9.0 mmol/L
Lactate 
dehydrogenase 
(LDH)
-----
-----
-----
≥ 3 × ULN


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
55
Variable
Sponsor Criteria
FDA Criteriaa
Very Low
Very High
Very Low
Very High
Magnesium
< 0.4 mmol/L
> 1.23 mmol/L
-----
-----
Phosphate
< 0.6 mmol/L
-----
-----
-----
Potassium
< 3 mmol/L
> 6 mmol/L
≤ 3.0 mmol/L
≥ 6.0 mmol/L
Protein (total)
-----
-----
≤ 50 g/L
≥ 100 g/L
Sodium
< 130 mmol/L
> 155 mmol/L
≤ 126 mmol/L
≥ 156 mmol/L
Triglycerides
-----
> 5.7 mmol/L
-----
≥ 3.3 mmol/L
Uric acid
-----
> 0.59 mmol/L
-----
Female:  
≥500 mcmol/L
Male:  
≥600 mcmol/L
Hy's Law lab 
criteria
ALT or AST ≥ 3 × 
ULN AND Total 
Bilirubin ≥ 2 × 
ULN
a.
Criteria requested by FDA DNP for Levodopa Carbidopa Intestinal Gel (LCIG) NDA 203952.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
56
Appendix C-3.
Potentially Clinically Significant (PCS) Special Lab Criteria
Variable
FDA Criteriaa
Very Low
Very High
Vitamin B12, serum
≤ 125 pmol/L
-----
Vitamin B6
≤ 16 nmol/L
≥ 145 nmol/L
Folate, serum
≤ 1.7 nmol/L
-----
Homocysteine
≤ 4.2 mcmol/L
≥ 14.0 mcmol/L
Methylmalonic acid (MMA)
-----
≥ 0.5 mcmol/L
a.
Criteria requested by FDA DNP for Levodopa Carbidopa Intestinal Gel (LCIG) NDA 203952.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
57
Appendix C-4.
Potentially Clinically Significant (PCS) Vital Sign and Weight 
Criteria
Variable
Sponsor Criteria
FDA Criteriaa
Very Low
Very High
Very Low
Very High
SBP (mmHg, 
supine and 
standing)
≤ 80 and 
decrease ≥ 45
from Baseline
≥ 160 and 
increase ≥ 45 
from Baseline
≥ 20 decrease from 
Baseline
≥ 20 increase 
from Baseline
≥ 40 decrease from 
Baseline
≥ 40 increase 
from Baseline
<90
> 140
> 160
DBP (mmHg, 
supine and 
standing)
≤ 50 and 
decrease ≥40 
from Baseline
≥ 95 and ≥ 
increase 40 from
Baseline
≥ 10 mmHg 
decrease from 
Baseline
≥ 10 mmHg 
increase from 
Baseline
≥ 20 mmHg 
decrease from 
Baseline
≥ 20 mmHg 
increase from 
Baseline
<50
>90
>100
Orthostatic SBP 
change (mmHg)
(standing-supine)
≤ 30 decrease 
from supine to 
standing
≤ -20
------
≤ -40
------
≥ 20 decrease from 
Baseline
≥ 20 increase 
from Baseline
≥ 40 mmHg 
decrease from 
Baseline
≥ 40 mmHg 
increase from 
Baseline
Orthostatic DBP
change (mmHg)
(standing-supine)
≤ 20 decrease 
from supine to 
standing
≤ -10
-----
≤ -20
------
≥ 10 decrease from 
Baseline
≥ 10 increase 
from Baseline
≥ 20 decrease from 
Baseline
≥ 20 increase 
from Baseline


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
58
Variable
Sponsor Criteria
FDA Criteriaa
Very Low
Very High
Very Low
Very High
Orthostatic SBP 
and DBP (mmHg)
Orthostatic SBP 
≤ -20 and orthostatic 
DBP ≤ -10
-----
Orthostatic SBP 
≤ -40 and orthostatic 
DBP ≤ -20
------
Orthostatic SBP ≥ 
20 decrease from 
Baseline and 
orthostatic DBP ≥ 
10 decrease from 
Baseline
------
Orthostatic SBP ≥ 
40 decrease from 
Baseline and 
orthostatic DBP ≥ 
20 decrease from 
Baseline
-----
Pulse rate (bpm, 
supine and 
standing)
≤ 45 and
decrease ≥ 35 
from Baseline
≥ 120 and 
increase ≥ 35 
from Baseline
≥ 15 decrease from 
Baseline
≥ 15 increase 
from Baseline
≥ 30 decrease from 
Baseline
≥ 30 increase 
from Baseline
≤ 60
≥ 100
Orthostatic pulse 
(bpm)
(standing-supine)
NA
Increase ≥ 30 
from supine to 
standing
≥ 15 decrease from 
Baseline
≥ 15 increase 
from Baseline
≥ 30 decrease from 
Baseline
≥ 30 increase 
from Baseline
Weight (kg)
≥ 7% decrease 
from Baseline
≥ 7% increase 
from Baseline
Temperature (°C)
≥ 38.3 and 
increase
≥ 1.1 from 
baseline
< 36.0
>38.0
a.
Criteria requested by FDA DNP for Levodopa Carbidopa Intestinal Gel (LCIG) NDA 203952.


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
59
Appendix C-5.
Criteria for Potentially Clinically Significant Electrocardiogram 
Values
ECG Variables
Definition of Potentially Clinically Significant
Very Low (VL)
Very High (VH)
Heart rate (bpm)
≤ 45 and decreased
≥ 35 from baseline
≥ 120 and increased
≥ 35 from baseline
PR (ms)
≤ 120
≥ 220
QTcF Interval (ms)
> 450
NA
> 500
> 480
>480 or Increased ≥ 60 from Baseline
Increased ≥ 30 from Baseline
Increased ≥ 60 from Baseline


ABBV-951
M15-736 – Statistical Analysis Plan
Version 3.0 – 19 October 2021
60
Appendix D.
Additional Adverse Event Search Criteria
Additional Adverse 
Event Searches
Search Criteria
COVID-19
COVID-19 SMQ – narrow search (code 20000237)
Abuse potential
Abuse Liability CMQ (code 10000001)
CMQ = Company MedDRA Query; SMQ = Standardized MedDRA Query