Trial Outcomes & Findings for A Study of LY3154207 in Participants With Dementia Due to Lewy Body Dementia (LBD) Associated With Idiopathic Parkinson's Disease (PD) or Dementia With Lewy Bodies (DLB) (NCT NCT03305809)

Last Updated: 2021-07-23

Results Overview

The CDR-CCB tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning which includes tests of attention (simple and choice reaction time, digit vigilance), working memory (spatial and numeric) and episodic memory (word recognition, picture recognition). Continuity of attention measures speed and accuracy and is calculated from 3 attentional tasks on the CDR computerized battery tests. For continuity of attention, the score range is -999 to 35. A high score reflects someone able to keep his/her mind on a single task for a prolonged period. A negative change from baseline reflects impairment compared to baseline. Data presented are model-based bayesian posterior mean response rates with 95% credible interval.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

344 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2021-07-23

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo administered orally once a day (QD).	10 Milligram (mg) LY3154207 Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 Participants received 75 mg LY3154207 administered orally QD.
Overall Study STARTED	86	86	85	87
Overall Study Received at Least One Dose of Study Drug	86	86	85	87
Overall Study COMPLETED	79	78	66	60
Overall Study NOT COMPLETED	7	8	19	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo administered orally once a day (QD).	10 Milligram (mg) LY3154207 Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 Participants received 75 mg LY3154207 administered orally QD.
Overall Study Adverse Event	2	2	6	6
Overall Study Death	0	0	1	1
Overall Study Lost to Follow-up	1	2	0	0
Overall Study Sponsor Decision	1	0	1	8
Overall Study Physician Decision	0	0	2	4
Overall Study Progressive Disease	0	0	1	0
Overall Study Protocol Violation	1	0	2	3
Overall Study Withdrawal due to Assessment Committee Decision	0	0	0	2
Overall Study Withdrawal by Subject	2	4	5	2
Overall Study Withdrawal due to Caregiver Circumstances	0	0	1	1

Baseline Characteristics

A Study of LY3154207 in Participants With Dementia Due to Lewy Body Dementia (LBD) Associated With Idiopathic Parkinson's Disease (PD) or Dementia With Lewy Bodies (DLB)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=86 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=86 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=85 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=87 Participants Participants received 75 mg LY3154207 administered orally QD.	Total n=344 Participants Total of all reporting groups
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	11 Participants n=21 Participants
Race (NIH/OMB) White	79 Participants n=5 Participants	81 Participants n=7 Participants	81 Participants n=5 Participants	85 Participants n=4 Participants	326 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment Canada	3 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	10 Participants n=21 Participants
Region of Enrollment Puerto Rico	5 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	15 Participants n=21 Participants
Region of Enrollment United States	78 Participants n=5 Participants	82 Participants n=7 Participants	78 Participants n=5 Participants	81 Participants n=4 Participants	319 Participants n=21 Participants
Age, Continuous	73.00 years STANDARD_DEVIATION 7.02 • n=5 Participants	72.50 years STANDARD_DEVIATION 6.70 • n=7 Participants	71.90 years STANDARD_DEVIATION 7.35 • n=5 Participants	73.00 years STANDARD_DEVIATION 5.21 • n=4 Participants	72.60 years STANDARD_DEVIATION 6.60 • n=21 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	13 Participants n=7 Participants	15 Participants n=5 Participants	15 Participants n=4 Participants	59 Participants n=21 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	73 Participants n=7 Participants	70 Participants n=5 Participants	72 Participants n=4 Participants	285 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants	11 Participants n=4 Participants	33 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants n=5 Participants	81 Participants n=7 Participants	76 Participants n=5 Participants	75 Participants n=4 Participants	309 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least 1 dose of study drug, who had the baseline efficacy assessment and had at least 1 postdose efficacy assessment.

Outcome measures

Outcome measures
Measure	Placebo n=69 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=74 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=65 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=54 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline in the Continuity of Attention (CoA) Composite Score of the Cognitive Drug Research Computerized Cognition Battery (CDR-CCB)	1.04 Units on a scale Interval -0.339 to 2.373	0.15 Units on a scale Interval -1.206 to 1.496	0.96 Units on a scale Interval -0.448 to 2.362	0.26 Units on a scale Interval -1.31 to 1.801

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline CGIC data.

The ADCS-CGIC is a validated categorical measure of change in a participant's clinical condition between baseline and follow-up visits; it is used to assess global clinical status. The ADCS CGIC score is based on direct examination of the participant and an interview of the caregiver. The rater should refer to the baseline ADCS-CGIC worksheets in making a rating. A skilled and experienced clinician who is blinded to treatment assignment rates the participant on a 7-point Likert scale, ranging from 1 (marked improvement) to 7 (marked worsening). 1= Very much better 2= Much better 3= A little better 4= Same 5= A little worse 6= Much worse 7= Very much worse. Least squares (LS) means were calculated using mixed model repeated measures adjusting for treatment + visit + treatment\*visit + age\*acheifl + age + concomitant use of acetylcholinesterase inhibitor (AChEI).

Outcome measures

Outcome measures
Measure	Placebo n=73 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=77 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=69 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=55 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline on the Alzheimer's Disease Cooperative Study-Clinician Global Impression of Change (ADCS-CGIC) Score	4.0 Score on a scale Standard Error 0.13	3.8 Score on a scale Standard Error 0.12	3.3 Score on a scale Standard Error 0.13	3.1 Score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline CDR-CCB PoA data.

The PoA is a composite score derived from the CDR-CCB that measures the intensity of concentration (ability to focus attention): the faster the responses, the more processes are being brought to bear upon the task. Power of attention is calculated from the sum of three cognitive function speed tests: simple reaction time, choice reaction time and the speed of detections in digit vigilance task. Score ranges from 450 milliseconds - 61500 milliseconds. A low score reflects a fast reaction time and a high intensity of concentration. A positive change from baseline reflects impairment compared to the baseline assessment Values are calculated by a computer and higher scores mean better outcome. LS means were calculated using mixed model repeated measures adjusting for baseline total Score + treatment + visit + treatment\*Visit + visit\*baseline total Score + age + concomitant use of AChEI.

Outcome measures

Outcome measures
Measure	Placebo n=69 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=73 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=65 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=54 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline on the CDR-CCB Power of Attention (PoA) Composite Score	64.14 Units on a scale Standard Error 48.681	-6.57 Units on a scale Standard Error 48.396	-42.88 Units on a scale Standard Error 49.804	-59.58 Units on a scale Standard Error 54.379

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline ADAS-Cog13 data.

The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS that was used as the primary efficacy measure consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS--Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. LS means were calculated using mixed model repeated measures adjusting for baseline total Score + treatment + visit + treatment\*Visit + visit\*baseline total Score + age + concomitant use of AChEI.

Outcome measures

Outcome measures
Measure	Placebo n=68 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=73 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=67 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=54 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline in the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)	-0.71 Units on a scale Standard Error 0.707	-1.11 Units on a scale Standard Error 0.691	-1.42 Units on a scale Standard Error 0.720	-1.59 Units on a scale Standard Error 0.799

SECONDARY outcome

Timeframe: Screening (Baseline), Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline MoCA data.

The Montreal Cognitive Assessment is a screening tool for global cognitive function with a total score ranging from 0 to 30 units on a scale. The MoCA is divided into 7 subscores (maximum possible subscore): visuospatial/executive (5 points), naming (3 points), memory (5 points for delayed recall), attention (6 points), language (3 points), abstraction (2 points) and orientation to time and place (6 points). A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome. LS means were calculated using mixed model repeated measures adjusting for baseline total Score + treatment + visit + treatment\*Visit + visit\*baseline total Score + age + concomitant use of AChEI.

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=76 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=68 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=55 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Screening in the Montreal Cognitive Assessment (MoCA) Score	0.90 Units on a scale Standard Error 0.432	1.34 Units on a scale Standard Error 0.423	1.12 Units on a scale Standard Error 0.448	1.84 Units on a scale Standard Error 0.496

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline NPI score data.

The NPI is a condition-specific measure designed to assess neuropsychiatric disturbances in people with Alzheimer Disease (AD),as well as other related dementing disorders.It assesses 12 behavioral disturbances,namely delusions,hallucinations,depression/dysphoria,anxiety,agitation/aggression,elation/euphoria,disinhibition,irritability/lability,apathy, aberrant motor activity, night-time behavior disturbances,and appetite/eating abnormalities.The frequency scored from 0 (never) to 4 (very frequently).The Severity scored from 0 (none) to 3 (marked).The domain score is obtained by multiplying frequency and severity scores.The total NPI score is sum total of all of individual domain scores (0-144).Higher score indiciates more abnormal behaviors.LS means were calculated using mixed model repeated measures adjusting for baseline total score + treatment + visit + treatment\*visit + visit\*baseline total score + age + concomitant use of AChEI.

Outcome measures

Outcome measures
Measure	Placebo n=73 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=77 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=66 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=55 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Total Score	-1.62 Units on a scale Standard Error 0.868	-2.24 Units on a scale Standard Error 0.852	-3.32 Units on a scale Standard Error 0.920	-2.37 Units on a scale Standard Error 1.005
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Delusions	0.13 Units on a scale Standard Error 0.124	-0.04 Units on a scale Standard Error 0.121	-0.25 Units on a scale Standard Error 0.130	0.02 Units on a scale Standard Error 0.144
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Hallucinations	-0.09 Units on a scale Standard Error 0.131	-0.11 Units on a scale Standard Error 0.128	-0.44 Units on a scale Standard Error 0.137	-0.38 Units on a scale Standard Error 0.151
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Agitation/Aggression	0.04 Units on a scale Standard Error 0.130	-0.06 Units on a scale Standard Error 0.126	-0.02 Units on a scale Standard Error 0.135	-0.20 Units on a scale Standard Error 0.148
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Depression/Dysphoria	-0.22 Units on a scale Standard Error 0.155	-0.16 Units on a scale Standard Error 0.151	-0.33 Units on a scale Standard Error 0.164	-0.35 Units on a scale Standard Error 0.179
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Anxiety	-0.15 Units on a scale Standard Error 0.141	-0.15 Units on a scale Standard Error 0.138	0.07 Units on a scale Standard Error 0.149	-0.22 Units on a scale Standard Error 0.163
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Elation/Euphoria	0.14 Units on a scale Standard Error 0.069	0.03 Units on a scale Standard Error 0.068	0.00 Units on a scale Standard Error 0.074	0.06 Units on a scale Standard Error 0.080
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Apathy/Indifference	-0.36 Units on a scale Standard Error 0.191	-0.81 Units on a scale Standard Error 0.186	-0.68 Units on a scale Standard Error 0.202	-0.55 Units on a scale Standard Error 0.220
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Disinhibition	-0.13 Units on a scale Standard Error 0.082	-0.11 Units on a scale Standard Error 0.080	0.21 Units on a scale Standard Error 0.087	-0.09 Units on a scale Standard Error 0.095
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Irritability/Lability	-0.19 Units on a scale Standard Error 0.130	-0.43 Units on a scale Standard Error 0.127	-0.25 Units on a scale Standard Error 0.137	0.02 Units on a scale Standard Error 0.150
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Aberrant Motor Behavior	-0.13 Units on a scale Standard Error 0.106	0.03 Units on a scale Standard Error 0.103	-0.23 Units on a scale Standard Error 0.112	-0.09 Units on a scale Standard Error 0.122
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Sleep/Nighttime Behavior Disorders	-0.19 Units on a scale Standard Error 0.287	0.00 Units on a scale Standard Error 0.278	-0.58 Units on a scale Standard Error 0.302	-0.30 Units on a scale Standard Error 0.329
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores Appetite/Eating Disorders	-0.37 Units on a scale Standard Error 0.270	-0.47 Units on a scale Standard Error 0.263	-0.80 Units on a scale Standard Error 0.284	-0.27 Units on a scale Standard Error 0.311

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline ESS data.

The ESS is a self-administered questionnaire with 8 questions. Each activity is scored on a scale ranging from 0-3, with 0 = would never fall asleep, and 3 = high chance of falling asleep. The total score ranges from 0-24, with a higher number representing an increased propensity for sleepiness. LS means were calculated using mixed model repeated measures adjusting for baseline total score + treatment + visit + treatment\*visit + visit\*baseline total score + age + concomitant use of AChEI.

Outcome measures

Outcome measures
Measure	Placebo n=73 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=77 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=67 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=55 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline in the Epworth Sleepiness Scale (ESS) Score	-0.33 Units on a scale Standard Error 0.437	-1.04 Units on a scale Standard Error 0.426	-1.21 Units on a scale Standard Error 0.452	-1.92 Units on a scale Standard Error 0.500

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline MDS-UPDRS data.

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) retains the four-scale structure with a reorganization of the various subscale; (Part I; 13 items) non-motor experiences of daily living, (Part II; 13) motor experiences of daily living, (Part III; 34) motor examination, and (Part IV; 6) motor complications. The scale range for MDS-UPDRS MDS-UPDRS Part I (non-motor experiences of daily living) and Part II (motor experiences of daily living) scores, total score was 0-52, with higher scores reflecting greater severity. For MDS-UPDRS Part III (motor examination) scores, the scale range for Part III Total Score was 0-132, with higher scores reflecting greater severity. LS means were calculated using mixed model repeated measures adjusting for baseline total score + treatment + visit + treatment\*visit + visit\*baseline total score + age + concomitant use of AChEI + levodopa equivalency dose (LED).

Outcome measures

Outcome measures
Measure	Placebo n=56 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=70 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=61 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=50 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline in the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I-III)	-0.18 Units on a scale Standard Error 2.112	-6.58 Units on a scale Standard Error 1.941	-7.56 Units on a scale Standard Error 2.084	-10.77 Units on a scale Standard Error 2.287

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline PDAQ-15 data.

The PDAQ-15 is a 15-item measure of instrumental activities of daily living (IADL) that are impacted by cognitive impairment in participants with parkinson's disease dementia (PDD). The PDAQ-15 is derived from the original 50-item scale, which has demonstrated test-retest reliability, construct validity, sensitivity, and specificity to Parkinson's disease (PD) cognitive impairment and the questionnaire is completed by the caregiver. The score range is 0 to 60, with higher scores indicating better function. LS means were calculated using mixed model repeated measures adjusting for baseline total score + treatment + visit + treatment\*visit + visit\*baseline total score + age + concomitant use of AChEI.

Outcome measures

Outcome measures
Measure	Placebo n=73 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=77 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=67 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=55 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline in the Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) Total Score	-0.32 Units on a scale Standard Error 0.976	0.23 Units on a scale Standard Error 0.961	2.09 Units on a scale Standard Error 1.018	1.24 Units on a scale Standard Error 1.128

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline D-KEFS data.

The DKEFS verbal fluency category switching test measures letter fluency, category fluency, and category switching. The score is the total number of correct words generated during each of the 60-second trials within the three conditions of the test. Scales scores vary from 0 min to N/A max (no concrete maximum). Higher score = higher ability in language processing. LS means were calculated using mixed model repeated measures adjusting for baseline total score + treatment + visit + treatment\*visit + visit\*baseline total score + age + concomitant use of AChEI.

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=76 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=66 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=53 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline in Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test Score	-0.19 Units on a scale Standard Error 0.280	0.44 Units on a scale Standard Error 0.271	0.88 Units on a scale Standard Error 0.292	0.30 Units on a scale Standard Error 0.325

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline MDS-UPDRS data.

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) retains the four-scale structure with a reorganization of the various subscale; (Part I; 13 items) non-motor experiences of daily living, (Part II; 13) motor experiences of daily living, (Part III; 34) motor examination, and (Part IV; 6) motor complications. The scale range for Part II total score was 0-52, with higher scores reflecting greater severity. For MDS-UPDRS Part III (motor examination) scores, the scale range for Part III Total Score was 0-132, with higher scores reflecting greater severity. LS means were calculated using mixed model repeated measures adjusting for baseline total score + treatment + visit + treatment\*visit + visit\*baseline total score + age + concomitant use of AChEI + LED dose.

Outcome measures

Outcome measures
Measure	Placebo n=75 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=77 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=69 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=54 Participants Participants received 75 mg LY3154207 administered orally QD.
Change in MDS-UPDRS Parts II (Motor Experiences of Daily Living) and III (Motor Exam) From Baseline to Week 12 Motor Experiences of Daily Living	0.28 Units on a scale Standard Error 0.656	-1.45 Units on a scale Standard Error 0.649	-2.08 Units on a scale Standard Error 0.700	-3.22 Units on a scale Standard Error 0.779
Change in MDS-UPDRS Parts II (Motor Experiences of Daily Living) and III (Motor Exam) From Baseline to Week 12 Motor Exam	-0.12 Units on a scale Standard Error 1.343	-3.39 Units on a scale Standard Error 1.240	-3.40 Units on a scale Standard Error 1.331	-4.35 Units on a scale Standard Error 1.434

SECONDARY outcome

Timeframe: Visit 3 (Day 1 stopping rules)

Population: All randomized participants who received at least one dose of study drug.

Number of participants who met the potentially clinically significant vital signs criteria at 3 consecutive time points at visit 3 were reported. In the event of an unacceptable rate of participants meeting day 1 stopping rules at other doses, adjustments to doses may be made for subsequently randomized participants at the discretion of the internal assessment committee (IAC).

Outcome measures

Outcome measures
Measure	Placebo n=86 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=86 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=65 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=87 Participants Participants received 75 mg LY3154207 administered orally QD.
Number of Participants Who Met the Potentially Clinically Significant Vital Signs Criteria at 3 Consecutive Time Points at Visit 3	0 Participants	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, 8 Hours Post Dose

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline BP data.

Systolic and diastolic blood pressure obtained from ambulatory blood pressure monitoring (ABPM) was evaluated. LS means were calculated using mixed model repeated measures adjusting for baseline + treatment + visit + visit\*baseline + treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=82 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=79 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=85 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline in Clinic Blood Pressure (BP) to 8 Hours Post Dose Sitting Systolic Blood Pressure	9.8 millimeter of mercury (mmHg) Standard Error 1.90	10.1 millimeter of mercury (mmHg) Standard Error 1.89	10.4 millimeter of mercury (mmHg) Standard Error 1.92	19.2 millimeter of mercury (mmHg) Standard Error 1.87
Change From Baseline in Clinic Blood Pressure (BP) to 8 Hours Post Dose Sitting Diastolic Blood Pressure	4.6 millimeter of mercury (mmHg) Standard Error 0.99	4.9 millimeter of mercury (mmHg) Standard Error 0.98	5.5 millimeter of mercury (mmHg) Standard Error 1.00	8.1 millimeter of mercury (mmHg) Standard Error 0.97

SECONDARY outcome

Timeframe: Baseline, 8 Hours Post Dose

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline pulse rate data.

Pulse rate obtained from ABPM was evaluated. Pulse rate measurements will occur at time 0 and every 60 minutes thereafter up to 8 hours and pulse rate measurements will be done in the seated position only. LS means were calculated using mixed model repeated measures adjusting for baseline + treatment + visit + visit\*baseline + treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=82 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=79 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=85 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline in Pulse Rate to 8 Hours Post Dose	-2.2 beats/min Standard Error 0.94	0.2 beats/min Standard Error 0.95	1.3 beats/min Standard Error 0.95	6.4 beats/min Standard Error 0.93

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline BP data.

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) obtained from ambulatory blood pressure monitoring (ABPM) was evaluated. LS means were calculated using mixed model repeated measures adjusting for baseline + treatment + visit + visit\*baseline + treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=74 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=77 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=65 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=56 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline In-clinic BP to Week 12 Sitting Systolic Blood Pressure	-1.2 millimeters of mercury (mmHg) Standard Error 1.22	0.5 millimeters of mercury (mmHg) Standard Error 1.19	0.1 millimeters of mercury (mmHg) Standard Error 1.29	3.0 millimeters of mercury (mmHg) Standard Error 1.38
Change From Baseline In-clinic BP to Week 12 Sitting Diastolic Blood Pressure	-0.9 millimeters of mercury (mmHg) Standard Error 0.71	-1.0 millimeters of mercury (mmHg) Standard Error 0.70	-0.2 millimeters of mercury (mmHg) Standard Error 0.75	0.3 millimeters of mercury (mmHg) Standard Error 0.80

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline pulse rate data.

Outcome measures

Outcome measures
Measure	Placebo n=74 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=77 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=65 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=56 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline in Pulse Rate to Week 12	-0.2 beats/min Standard Error 0.67	0.3 beats/min Standard Error 0.66	1.5 beats/min Standard Error 0.71	2.6 beats/min Standard Error 0.75

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline BP data.

Systolic and diastolic blood pressure obtained from ABPM was evaluated. Participants followed a standardized measurement protocol for home blood pressure measurement, involving three consecutive measurements, taken one minute apart after a five-minute seated resting period. LS means were calculated using mixed model repeated measures adjusting for baseline + treatment + visit + visit\*baseline + treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=51 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=41 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=41 Participants Participants received 75 mg LY3154207 administered orally QD.
Change in Home Blood Pressure Measurement (HBPM), for SBP, DBP From Baseline to Week 12 Sitting Systolic Blood Pressure	-1.1 mmHg Standard Error 2.52	-8.2 mmHg Standard Error 2.40	2.0 mmHg Standard Error 2.58	-2.2 mmHg Standard Error 2.62
Change in Home Blood Pressure Measurement (HBPM), for SBP, DBP From Baseline to Week 12 Sitting Diastolic Blood Pressure	1.5 mmHg Standard Error 1.50	-2.8 mmHg Standard Error 1.45	1.0 mmHg Standard Error 1.55	-0.8 mmHg Standard Error 1.58

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline pulse rate data.

Pulse rate obtained from ABPM was evaluated. Pulse rate measurements will occur at time 0 and every 60 minutes thereafter up to week 12 and pulse rate measurements will be done in the seated position only. LS means were calculated using mixed model repeated measures adjusting for baseline + treatment + visit + visit\*baseline + treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=51 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=41 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=41 Participants Participants received 75 mg LY3154207 administered orally QD.
Change in HBPM for Pulse Rate From Baseline to Week 12	1.4 beats/min Standard Error 1.52	1.4 beats/min Standard Error 1.47	0.7 beats/min Standard Error 1.59	0.8 beats/min Standard Error 1.62

SECONDARY outcome

Timeframe: Week 12, Follow-up (2 Weeks after Week 12)

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline PWC-20 data.

The Penn PWC-20 is a 20-item checklist originally developed to assess the severity of withdrawal symptoms in anxiolytic medication discontinuation. To determine a change in the Intensity of Discontinuation symptoms, the PWC-20 administered by a trained clinician/rater to assess the intensity of discontinuation symptoms. The assessment has 20 items evaluated to detect withdrawal symptoms. Symptoms are rated on a scale of 0-3. 0\. Not present 1. Mild 2. Moderate 3. Severe Total scores range from 0 to 60 with higher scores indicating more severe symptoms.Least squares (LS) means were calculated using mixed model analysis of covariance (ANCOVA) adjusting for predose, sequence, period, day, time, treatment, and treatment\*time as fixed effects and participant within sequence and treatment as random effect.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=33 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=32 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=24 Participants Participants received 75 mg LY3154207 administered orally QD.
Change From Baseline in the Physician Withdrawal Checklist (PWC)-20 Total Score From Week 12 to In-Clinic Follow-up Visit Week 12	-1.51 Units on a scale Standard Error 0.670	-0.53 Units on a scale Standard Error 0.690	-0.47 Units on a scale Standard Error 0.701	0.05 Units on a scale Standard Error 0.811
Change From Baseline in the Physician Withdrawal Checklist (PWC)-20 Total Score From Week 12 to In-Clinic Follow-up Visit Follow-up	-1.27 Units on a scale Standard Error 0.844	0.12 Units on a scale Standard Error 0.877	0.13 Units on a scale Standard Error 0.904	3.32 Units on a scale Standard Error 1.040

SECONDARY outcome

Timeframe: Day 1: 1-3 hours post-dose; Day 7, Day 14 and Day 42: post-dose; Day 84: pre-dose

Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.

Trough measurements of LY3154207 concentration in plasma at Day 1, Day 7, Day 14, Day 42 and Day 84 was evaluated.

Outcome measures

Outcome measures
Measure	Placebo n=86 Participants Participants received placebo administered orally QD.	10 mg LY3154207 n=77 Participants Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=81 Participants Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 Participants received 75 mg LY3154207 administered orally QD.
Pharmacokinetics (PK): Steady-State Trough Plasma Concentrations of LY3154207 Day 1	34.95 nanogram per milliliter (ng/mL) Standard Deviation 28.82	89.36 nanogram per milliliter (ng/mL) Standard Deviation 88.03	223.30 nanogram per milliliter (ng/mL) Standard Deviation 208.63	—
Pharmacokinetics (PK): Steady-State Trough Plasma Concentrations of LY3154207 Day 7	50.53 nanogram per milliliter (ng/mL) Standard Deviation 38.20	123.61 nanogram per milliliter (ng/mL) Standard Deviation 100.89	297.35 nanogram per milliliter (ng/mL) Standard Deviation 242.47	—
Pharmacokinetics (PK): Steady-State Trough Plasma Concentrations of LY3154207 Day 14	45.85 nanogram per milliliter (ng/mL) Standard Deviation 33.61	129.24 nanogram per milliliter (ng/mL) Standard Deviation 89.24	321.65 nanogram per milliliter (ng/mL) Standard Deviation 253.11	—
Pharmacokinetics (PK): Steady-State Trough Plasma Concentrations of LY3154207 Day 42	44.25 nanogram per milliliter (ng/mL) Standard Deviation 33.93	149.22 nanogram per milliliter (ng/mL) Standard Deviation 122.01	333.40 nanogram per milliliter (ng/mL) Standard Deviation 257.74	—
Pharmacokinetics (PK): Steady-State Trough Plasma Concentrations of LY3154207 Day 84	25.01 nanogram per milliliter (ng/mL) Standard Deviation 30.43	59.39 nanogram per milliliter (ng/mL) Standard Deviation 58.20	126.53 nanogram per milliliter (ng/mL) Standard Deviation 197.67	—

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 20 other events

Deaths: 0 deaths

10 mg LY3154207

Serious events: 5 serious events

Other events: 26 other events

Deaths: 0 deaths

30 mg LY3154207

Serious events: 3 serious events

Other events: 30 other events

Deaths: 1 deaths

75 mg LY3154207

Serious events: 10 serious events

Other events: 43 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=86 participants at risk Participants received placebo administered orally QD.	10 mg LY3154207 n=86 participants at risk Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=85 participants at risk Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=87 participants at risk Participants received 75 mg LY3154207 administered orally QD.
Gastrointestinal disorders Diarrhoea	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	2.3% 2/86 • Number of events 2 • Up To 4 Months All randomized participants who received at least one dose of study drug.	5.9% 5/85 • Number of events 7 • Up To 4 Months All randomized participants who received at least one dose of study drug.	2.3% 2/87 • Number of events 4 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	3.5% 3/86 • Number of events 5 • Up To 4 Months All randomized participants who received at least one dose of study drug.	2.3% 2/86 • Number of events 2 • Up To 4 Months All randomized participants who received at least one dose of study drug.	8.2% 7/85 • Number of events 8 • Up To 4 Months All randomized participants who received at least one dose of study drug.	9.2% 8/87 • Number of events 9 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	3.5% 3/86 • Number of events 3 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	2.4% 2/85 • Number of events 2 • Up To 4 Months All randomized participants who received at least one dose of study drug.	8.0% 7/87 • Number of events 8 • Up To 4 Months All randomized participants who received at least one dose of study drug.
General disorders Fatigue	4.7% 4/86 • Number of events 4 • Up To 4 Months All randomized participants who received at least one dose of study drug.	2.3% 2/86 • Number of events 2 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/85 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	10.3% 9/87 • Number of events 9 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	2.3% 2/86 • Number of events 2 • Up To 4 Months All randomized participants who received at least one dose of study drug.	5.8% 5/86 • Number of events 5 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/85 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	4.7% 4/86 • Number of events 10 • Up To 4 Months All randomized participants who received at least one dose of study drug.	14.0% 12/86 • Number of events 17 • Up To 4 Months All randomized participants who received at least one dose of study drug.	7.1% 6/85 • Number of events 7 • Up To 4 Months All randomized participants who received at least one dose of study drug.	13.8% 12/87 • Number of events 16 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Nervous system disorders Dizziness	4.7% 4/86 • Number of events 4 • Up To 4 Months All randomized participants who received at least one dose of study drug.	4.7% 4/86 • Number of events 4 • Up To 4 Months All randomized participants who received at least one dose of study drug.	7.1% 6/85 • Number of events 6 • Up To 4 Months All randomized participants who received at least one dose of study drug.	10.3% 9/87 • Number of events 10 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Nervous system disorders Dyskinesia	2.3% 2/86 • Number of events 2 • Up To 4 Months All randomized participants who received at least one dose of study drug.	2.3% 2/86 • Number of events 2 • Up To 4 Months All randomized participants who received at least one dose of study drug.	3.5% 3/85 • Number of events 3 • Up To 4 Months All randomized participants who received at least one dose of study drug.	5.7% 5/87 • Number of events 6 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	2.3% 2/86 • Number of events 2 • Up To 4 Months All randomized participants who received at least one dose of study drug.	9.4% 8/85 • Number of events 8 • Up To 4 Months All randomized participants who received at least one dose of study drug.	8.0% 7/87 • Number of events 8 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Psychiatric disorders Hallucination	4.7% 4/86 • Number of events 4 • Up To 4 Months All randomized participants who received at least one dose of study drug.	2.3% 2/86 • Number of events 2 • Up To 4 Months All randomized participants who received at least one dose of study drug.	5.9% 5/85 • Number of events 5 • Up To 4 Months All randomized participants who received at least one dose of study drug.	10.3% 9/87 • Number of events 9 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	4.7% 4/86 • Number of events 4 • Up To 4 Months All randomized participants who received at least one dose of study drug.	4.7% 4/85 • Number of events 4 • Up To 4 Months All randomized participants who received at least one dose of study drug.	5.7% 5/87 • Number of events 5 • Up To 4 Months All randomized participants who received at least one dose of study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Placebo n=86 participants at risk Participants received placebo administered orally QD.	10 mg LY3154207 n=86 participants at risk Participants received 10 mg LY3154207 administered orally QD.	30 mg LY3154207 n=85 participants at risk Participants received 30 mg LY3154207 administered orally QD.	75 mg LY3154207 n=87 participants at risk Participants received 75 mg LY3154207 administered orally QD.
Cardiac disorders Angina pectoris	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure congestive	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Oesophagitis	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Pancreatitis	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/85 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
General disorders Chest pain	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
General disorders Death	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Infections and infestations Cellulitis	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Infections and infestations Herpes zoster meningoencephalitis	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Infections and infestations Localised infection	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Infections and infestations Pseudomonas infection	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Infections and infestations Septic shock	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/85 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/85 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperammonaemia	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/85 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Nervous system disorders Cerebrovascular accident	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Nervous system disorders Dizziness	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Nervous system disorders Facial paralysis	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Nervous system disorders Hemianaesthesia	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Nervous system disorders Hemiparesis	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 2 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Nervous system disorders Hypertensive encephalopathy	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Nervous system disorders Syncope	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Psychiatric disorders Confusional state	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Psychiatric disorders Disorientation	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Tubulointerstitial nephritis	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.2% 1/86 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/87 • Up To 4 Months All randomized participants who received at least one dose of study drug.
Vascular disorders Hypertension	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/86 • Up To 4 Months All randomized participants who received at least one dose of study drug.	0.00% 0/85 • Up To 4 Months All randomized participants who received at least one dose of study drug.	1.1% 1/87 • Number of events 1 • Up To 4 Months All randomized participants who received at least one dose of study drug.