PRESENCE: 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)

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03305809
• Collaborator: (none)
• Enrollment: 344
• Locations: 77
• Arms: 4
• Actual Duration (Months): 32
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A randomized placebo-controlled trial to evaluate the safety and efficacy of three doses of study drug LY3154207 treated for 12 weeks in participants with mild-to-moderate dementia associated with LBD (PDD or DLB).

Condition or Disease	Intervention/Treatment	Phase
Lewy Body Dementia	Drug: LY3154207; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 344 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of LY3154207 on Cognition in Mild-to-Moderate Dementia Due to Lewy Body Dementia (LBD) Associated With Idiopathic Parkinson's Disease (PD) or Dementia With Lewy Bodies (DLB)
• Actual Study Start Date: Nov 9, 2017
• Actual Primary Completion Date: Jul 10, 2020
• Actual Study Completion Date: Jul 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo administered orally once a day (QD).	Drug: Placebo; Administered orally.
Experimental: 10 milligram (mg) LY3154207 Participants received 10 mg LY3154207 administered orally QD.	Drug: LY3154207; Administered orally.
Experimental: 30 mg LY3154207 Participants received 30 mg LY3154207 administered orally QD.	Drug: LY3154207; Administered orally.
Experimental: 75 mg LY3154207 Participants received 75 mg LY3154207 administered orally QD.	Drug: LY3154207; Administered orally.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Continuity of Attention (CoA) Composite Score of the Cognitive Drug Research Computerized Cognition Battery (CDR-CCB) [Baseline, Week 12]

   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.

Secondary Outcome Measures

1. Change From Baseline on the Alzheimer's Disease Cooperative Study-Clinician Global Impression of Change (ADCS-CGIC) Score [Baseline, Week 12]

   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).

2. Change From Baseline on the CDR-CCB Power of Attention (PoA) Composite Score [Baseline, Week 12]

   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.

3. Change From Baseline in the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) [Baseline, Week 12]

   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.

4. Change From Screening in the Montreal Cognitive Assessment (MoCA) Score [Screening (Baseline), Week 12]

   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.

5. Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores [Baseline, Week 12]

   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.

6. Change From Baseline in the Epworth Sleepiness Scale (ESS) Score [Baseline, Week 12]

   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.

7. Change From Baseline in the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I-III) [Baseline, Week 12]

   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).

8. Change From Baseline in the Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) Total Score [Baseline, Week 12]

   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.

9. Change From Baseline in Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test Score [Baseline, Week 12]

   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.

10. Change in MDS-UPDRS Parts II (Motor Experiences of Daily Living) and III (Motor Exam) From Baseline to Week 12 [Baseline, Week 12]

    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.

11. Number of Participants Who Met the Potentially Clinically Significant Vital Signs Criteria at 3 Consecutive Time Points at Visit 3 [Visit 3 (Day 1 stopping rules)]

    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).

12. Change From Baseline in Clinic Blood Pressure (BP) to 8 Hours Post Dose [Baseline, 8 Hours Post Dose]

    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.

13. Change From Baseline in Pulse Rate to 8 Hours Post Dose [Baseline, 8 Hours Post Dose]

    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.

14. Change From Baseline In-clinic BP to Week 12 [Baseline, Week 12]

    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.

15. Change From Baseline in Pulse Rate to Week 12 [Baseline, Week 12]

    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.

16. Change in Home Blood Pressure Measurement (HBPM), for SBP, DBP From Baseline to Week 12 [Baseline, Week 12]

    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.

17. Change in HBPM for Pulse Rate From Baseline to Week 12 [Baseline, Week 12]

    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.

18. Change From Baseline in the Physician Withdrawal Checklist (PWC)-20 Total Score From Week 12 to In-Clinic Follow-up Visit [Week 12, Follow-up (2 Weeks after Week 12)]

    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 Mild Moderate 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.

19. Pharmacokinetics (PK): Steady-State Trough Plasma Concentrations of LY3154207 [Day 1: 1-3 hours post-dose; Day 7, Day 14 and Day 42: post-dose; Day 84: pre-dose]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have dementia as defined by a decline in cognitive function, which in the opinion of the investigator has resulted in functional impairment.

• Meet diagnostic criteria for PD per MDS criteria or DLB per 4th Consensus Report of the DLB Consortium.

• Have a score on the MoCA of 10 - 23.

• Are Modified Hoehn and Yahr Stages 0 - 4.

• Have a blood pressure (BP) or pulse rate at screening and randomization, as determined by three sequential BP/pulse rate measurements in a seated position:

• Participants <60 years old:

1. A mean systolic BP less than or equal to 140 millimeters of mercury (mmHg), a mean diastolic BP less than or equal to 90 mmHg and a mean pulse rate less than or equal 90 beats/minute in a seated position.

2. Each of the 3 systolic BP measurement must be less than 180 mmHg

• Participants ≥60 years old:

1. A mean systolic BP less than or equal to 150 mmHg, a mean diastolic BP less than or equal to 90 mmHg and a mean pulse rate less than or equal to 90 beats/min in a seated position.

2. Each of the 3 systolic BP measurement must be less than 180 mmHg

• If on anti-parkinsonian agents, participants must be on stable dosage for at least 3 weeks prior to screening, and should remain on stable doses during the course of the study.

• If on medications affecting cognition (rivastigmine, galantamine, donepezil, memantine), participants must be on stable dosage for at least 3 weeks prior to screening and should remain at a stable dosage during the course of the study.

• If on antidepressant medications, participants must be on stable dosage for at least 3 weeks prior to screening and should remain at a stable dosage during the course of the study.

• If on clozapine, quetiapine, and pimavanserin to address drug induced or disease related psychosis, participants must be on stable dosage for 3 weeks prior to screening and should remain at a stable dosage during the course of the study.

• If on antihypertensive medications, participants must be on stable dosage for at least 3 weeks prior to screening.

• Men should use appropriate contraception.

• All participants must have a reliable caregiver who is in frequent contact with the participant (defined as at least 10 hours per week) and will accompany the participant to screening, baseline, day 7, day 42, day 84 and follow-up.

Exclusion Criteria:

• Are women of childbearing potential.

• Have significant central nervous system or psychiatric disease, other than PD or DLB, that in the investigator's opinion may affect cognition or the ability to complete the study.

• Have a history in the last 6 months of transient ischemic attacks or ischemic stroke.

• Have a history of intra cerebral hemorrhage due to hypertension.

• Have a history of hypertensive encephalopathy.

• Have atypical or secondary parkinsonism due to drugs (e.g., antipsychotics) or disease (such as progressive supranuclear palsy, essential tremor, multiple system atrophy (e.g. striatonigral degeneration, olivopontocerebellar atrophy), or postencephalitic parkinsonism).

• Have a current implantable intracranial stimulator or history of intracranial ablation surgery (e.g., subthalamic, globus pallidus-internal segment [GPi]).

• Have a history of substance abuse within the past 1 year (drug categories defined by the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition [DSM-5], and/or substance dependence within the past 1 year, not including caffeine and nicotine.

• Have a serious or unstable medical illness, other than idiopathic LBD (PDD or DLB), including cardiovascular, hepatic, respiratory, hematologic, endocrinologic, neurologic, or renal disease, or clinically significant laboratory or electrocardiogram (ECG) abnormality as determined by the investigator.

• Have a history in the last 6 months of exertional angina, unstable angina, myocardial infarction, and acute coronary syndrome.

• Have a history of heart failure of either New York Heart Association Class III or IV.

• A history of additional risk factors for Torsades de Pointes (TdP; [e.g., chronic hypokalemia, family history of Long QT Syndrome]).

• Participants with acute liver disease (e.g. acute viral hepatitis, alcoholic hepatitis); participants with a known chronic liver disease (e.g. hepatitis B, C, alcoholic liver disease, cirrhosis); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or higher than 2X upper limit of normal (ULN); total bilirubin (TBL) equal to or higher than 1.5X ULN; (except for participants with Gilbert's syndrome); or alkaline phosphatase (ALP) equal to or higher than 2X ULN.

• Participants have answered 'yes' to either Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) or Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the Columbia Suicide Severity Rating Scale (C-SSRS)- Children's version, or answer "yes" to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt).

• Have used antipsychotic medications, with the exception of clozapine, quetiapine, pimavanserin in the 6 months prior to screening and at any time during the course of the study.

• Have used anticholinergics trihexyphenidyl and benztropine in the 4 weeks prior to screening and at any time during the course of the study.

• Have motor conditions for which the antiparkinsonian treatment is expected to change during the course of the study, as well as unpredictable motor fluctuations that in the investigator's opinion would interfere with administering assessments.

• Are taking any medications or food, herbal or dietary supplements that are inhibitors (e.g., ketoconazole, grapefruit juice), or strong/moderate inducers of cytochrome P450 3A4 (CYP3A4) (e.g., rifampicin) or are unable or unwilling to discontinue usage of them 4 weeks prior to first dose of study drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Birmingham	Birmingham	Alabama	United States	35233
2	Barrow Neurological Institute	Phoenix	Arizona	United States	85013
3	Mayo Clinic of Scottsdale	Scottsdale	Arizona	United States	85259
4	Banner Sun Health Research Institute	Sun City	Arizona	United States	85351
5	University of Arizona Health Sciences	Tucson	Arizona	United States	85724
6	Parkinson'S & Movement Disorder Institute	Fountain Valley	California	United States	92708
7	University of CA, Irvine	Irvine	California	United States	92697
8	Collaborative Neuroscience Network - CNS	Long Beach	California	United States	90806
9	University of Southern California School of Medicine	Los Angeles	California	United States	90033
10	Pacific Neuroscience Medical Group	Oxnard	California	United States	93030
11	Stanford Neuroscience Health Center	Palo Alto	California	United States	94304
12	SC3 Research Group Inc Pasadena	Pasadena	California	United States	91105
13	SC3 Research Group Inc Reseda	Reseda	California	United States	91335
14	University of California, Davis - Health Systems	Sacramento	California	United States	95817
15	University of Colorado Hospital	Aurora	Colorado	United States	80045
16	Denver Neurological Research	Denver	Colorado	United States	80210
17	Rocky Mountain Movement Disorders Center	Englewood	Colorado	United States	80113
18	New England Institute for Clinical Research	Stamford	Connecticut	United States	06905
19	Hartford Healthcare Chase Movement Disorders Center	Vernon	Connecticut	United States	06066
20	Christiana Care Health Service	Newark	Delaware	United States	19713
21	Georgetown University Hospital	Washington	District of Columbia	United States	20007
22	JEM Research Institute	Atlantis	Florida	United States	33462
23	Visionary Investigators Network	Aventura	Florida	United States	33180
24	Parkinson's Disease and Movement Disorders	Boca Raton	Florida	United States	33486
25	Norman Fixel Institute for Neurological Diseases (FIND)	Gainesville	Florida	United States	32608
26	ClinCloud, LLC	Maitland	Florida	United States	32751
27	Visionary Investigators Network	Miami	Florida	United States	33133
28	Suncoast Research Group, LLC	Miami	Florida	United States	33135
29	VIN - Victor Faradji	Miami	Florida	United States	33176
30	Collier Neurologic Specialists	Naples	Florida	United States	34105
31	Renstar Medical Research	Ocala	Florida	United States	34470
32	Compass Research	Orlando	Florida	United States	32806
33	Neurology Associates of Ormond Beach	Ormond Beach	Florida	United States	32174
34	Visionary Investigators Network -VIN-Margarita Almeida	Pembroke Pines	Florida	United States	33026
35	Axiom Research	Tampa	Florida	United States	33609
36	Emory University	Atlanta	Georgia	United States	30329
37	Atlanta Center of Medical Research	Atlanta	Georgia	United States	30331
38	Central DuPage Hospital	Winfield	Illinois	United States	60190
39	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
40	Josephson Wallack Munshower Neurology	Indianapolis	Indiana	United States	46256
41	University of Kansas School of Medicine	Kansas City	Kansas	United States	66160
42	Maine Neurology	Scarborough	Maine	United States	04074
43	New England Neurological Associates, PC	Methuen	Massachusetts	United States	01844
44	University of Michigan	Ann Arbor	Michigan	United States	48109
45	QUEST Research Institute	Farmington Hills	Michigan	United States	48334
46	Clinical Research Professionals	Chesterfield	Missouri	United States	63005
47	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
48	Cleveland Clinic of Las Vegas	Las Vegas	Nevada	United States	89106
49	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0001
50	The Cognitive and Research Center of NJ	Springfield	New Jersey	United States	07081
51	Bio Behavioral Health	Toms River	New Jersey	United States	08755
52	Dent Neurological Institute	Amherst	New York	United States	14226
53	Alzheimer's Disease and Memory Disorders Center	Buffalo	New York	United States	14203
54	Adirondack Medical Research	Glens Falls	New York	United States	12801
55	Parker Jewish Insititue for Heatlh Care and Rehabilition	New Hyde Park	New York	United States	11040
56	NYU Langone	New York	New York	United States	10016
57	Carolinas Healthcare System	Charlotte	North Carolina	United States	28207
58	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
59	Penn State Univ. Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
60	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107
61	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
62	Abington Neurological Associates	Willow Grove	Pennsylvania	United States	19090
63	Medical University of South Carolina	Charleston	South Carolina	United States	29425
64	Texas Neurology, PA	Dallas	Texas	United States	75214
65	Neurology Consultants of Dallas, PA	Dallas	Texas	United States	75243
66	Baylor College of Medicine	Houston	Texas	United States	77030
67	Houston Methodist Research Ins	Houston	Texas	United States	77030
68	Sentara Neurology Specialists	Virginia Beach	Virginia	United States	23456
69	Northwest Clinical Research Center	Bellevue	Washington	United States	98007-4209
70	Evergreen Professional Plaza	Kirkland	Washington	United States	98034
71	University of Wisconsin-Madison Hospital and Health Clinic	Madison	Wisconsin	United States	53705
72	Toronto Memory Program	Toronto	Ontario	Canada	M3B 2S7
73	Ottawa Hospital Research Institute	Ottawa		Canada	K1Y 4E9
74	Santa Cruz Behavioral PSC	Bayamón		Puerto Rico	00961-6911
75	Cortex, PSC	Las Piedras		Puerto Rico	00771
76	Instituto de Neurologia Dra. Ivonne Fraga	San Juan		Puerto Rico	00918
77	University of Puerto Rico	San Juan		Puerto Rico	00936

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Jan 25, 2019
• Statistical Analysis Plan - Feb 8, 2021

More Information

Additional Information:

• 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) (PRESENCE)

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03305809
• Other Study ID Numbers: 16261; I7S-MC-HBEH
• First Posted: Oct 10, 2017
• Last Update Posted: Jul 23, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eli Lilly and Company: Parkinson Disease Dementia; Parkinson Disease; Dopamine; Cognition; Lewy Body Dementia; Dementia with Lewy Bodies
• Additional relevant MeSH terms: Parkinson Disease; Dementia; Alzheimer Disease; Lewy Body Disease

Study Results

Participant Flow

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

Baseline Characteristics

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207	Total
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.	Total of all reporting groups
Overall Participants	86	86	85	87	344
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.00 (7.02)	72.50 (6.70)	71.90 (7.35)	73.00 (5.21)	72.60 (6.60)
Sex: Female, Male (Count of Participants)
Female	16 18.6%	13 15.1%	15 17.6%	15 17.2%	59 17.2%
Male	70 81.4%	73 84.9%	70 82.4%	72 82.8%	285 82.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 9.3%	5 5.8%	9 10.6%	11 12.6%	33 9.6%
Not Hispanic or Latino	77 89.5%	81 94.2%	76 89.4%	75 86.2%	309 89.8%
Unknown or Not Reported	1 1.2%	0 0%	0 0%	1 1.1%	2 0.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.2%	1 1.2%	0 0%	0 0%	2 0.6%
Asian	2 2.3%	1 1.2%	1 1.2%	0 0%	4 1.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	4 4.7%	3 3.5%	2 2.4%	2 2.3%	11 3.2%
White	79 91.9%	81 94.2%	81 95.3%	85 97.7%	326 94.8%
More than one race	0 0%	0 0%	1 1.2%	0 0%	1 0.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Canada	3 3.5%	2 2.3%	3 3.5%	2 2.3%	10 2.9%
Puerto Rico	5 5.8%	2 2.3%	4 4.7%	4 4.6%	15 4.4%
United States	78 90.7%	82 95.3%	78 91.8%	81 93.1%	319 92.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Continuity of Attention (CoA) Composite Score of the Cognitive Drug Research Computerized Cognition Battery (CDR-CCB)
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	69	74	65	54
Least Squares Mean (95% Confidence Interval) [Units on a scale]	1.04	0.15	0.96	0.26

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -2.776 to 0.969
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analyses were conducted using a bayesian mixed-model repeated measures (MMRM), and posterior mean change difference is reported.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -1.996 to 1.879
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analyses were conducted using a bayesian MMRM, and posterior mean change difference is reported.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-0.78
	Confidence Interval	(2-Sided) 95%; -2.873 to 1.277
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analyses were conducted using a bayesian MMRM, and posterior mean change difference is reported.

2. Secondary Outcome

Title	Change From Baseline on the Alzheimer's Disease Cooperative Study-Clinician Global Impression of Change (ADCS-CGIC) Score
Description	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).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	73	77	69	55
Least Squares Mean (Standard Error) [Score on a scale]	4.0 (0.13)	3.8 (0.12)	3.3 (0.13)	3.1 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.273
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.54 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.02 to -0.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.29 to -0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline on the CDR-CCB Power of Attention (PoA) Composite Score
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	69	73	65	54
Least Squares Mean (Standard Error) [Units on a scale]	64.14 (48.681)	-6.57 (48.396)	-42.88 (49.804)	-59.58 (54.379)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.303
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-70.71
	Confidence Interval	(2-Sided) 95%; -205.53 to 64.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 68.495
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.125
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-107.02
	Confidence Interval	(2-Sided) 95%; -244.09 to 30.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 69.647
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.091
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-123.72
	Confidence Interval	(2-Sided) 95%; -267.18 to 19.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 72.892
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	68	73	67	54
Least Squares Mean (Standard Error) [Units on a scale]	-0.71 (0.707)	-1.11 (0.691)	-1.42 (0.720)	-1.59 (0.799)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.686
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -2.34 to 1.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.985
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.485
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -2.70 to 1.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.011
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.406
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -2.98 to 1.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.064
	Estimation Comments

5. Secondary Outcome

Title	Change From Screening in the Montreal Cognitive Assessment (MoCA) Score
Description	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.
Time Frame	Screening (Baseline), Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	71	76	68	55
Least Squares Mean (Standard Error) [Units on a scale]	0.90 (0.432)	1.34 (0.423)	1.12 (0.448)	1.84 (0.496)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.464
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95%; -0.74 to 1.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.603
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.720
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95%; -1.00 to 1.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.623
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.149
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; -0.34 to 2.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.655
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

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

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Total Score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.607
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.62
	Confidence Interval	(2-Sided) 95%; -3.01 to 1.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.213
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Total Score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.180
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.70
	Confidence Interval	(2-Sided) 95%; -4.19 to 0.79
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.265
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Total Score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.572
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.75
	Confidence Interval	(2-Sided) 95%; -3.36 to 1.86
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.325
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Delusions
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.320
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.51 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.173
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Delusions
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.73 to -0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.180
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Delusions
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.558
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.49 to 0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.190
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Hallucinations
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.924
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.38 to 0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.182
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Hallucinations
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.061
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -0.73 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.189
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Hallucinations
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.148
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.68 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.199
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Agitation/Aggression
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.552
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.46 to 0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.180
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Agitation/Aggression
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.735
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.43 to 0.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.188
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Agitation/Aggression
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.224
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -0.63 to 0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.197
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Depression/Dysphoria
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.783
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.216
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Depression/Dysphoria
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.640
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.55 to 0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.226
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Depression/Dysphoria
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.592
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.59 to 0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.236
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Anxiety
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.993
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.39 to 0.39
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.197
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Anxiety
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.290
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.205
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Anxiety
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.722
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.50 to 0.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.215
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Elation/Euphoria
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.246
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.097
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Elation/Euphoria
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.175
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.34 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.101
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Elation/Euphoria
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.482
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.28 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.106
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Apathy/Indifference
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.091
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95%; -0.97 to 0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.266
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Apathy/Indifference
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.248
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -0.87 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.278
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Apathy/Indifference
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.516
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.76 to 0.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.290
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Disinhibition
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.875
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.21 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.114
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Disinhibition
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; 0.10 to 0.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.119
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Disinhibition
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.761
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.21 to 0.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.125
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Irritability/Lability
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.183
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -0.60 to 0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.181
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Irritability/Lability
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.765
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.43 to 0.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.189
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Irritability/Lability
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.279
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; -0.18 to 0.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.198
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Aberrant Motor Behavior
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.252
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.147
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Aberrant Motor Behavior
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.526
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.154
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Aberrant Motor Behavior
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.800
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.28 to 0.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.161
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Sleep/Nighttime Behavior Disorders
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.623
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95%; -0.59 to 0.98
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.400
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Sleep/Nighttime Behavior Disorders
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.354
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -1.21 to 0.44
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.418
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Sleep/Nighttime Behavior Disorders
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.809
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.97 to 0.75
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.437
	Estimation Comments

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Appetite/Eating Disorders
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.790
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -0.84 to 0.64
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.376
	Estimation Comments

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Appetite/Eating Disorders
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.280
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -1.20 to 0.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.392
	Estimation Comments

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Appetite/Eating Disorders
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.797
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; -0.70 to 0.92
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.412
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in the Epworth Sleepiness Scale (ESS) Score
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	73	77	67	55
Least Squares Mean (Standard Error) [Units on a scale]	-0.33 (0.437)	-1.04 (0.426)	-1.21 (0.452)	-1.92 (0.500)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.247
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -1.91 to 0.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.610
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.164
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.88
	Confidence Interval	(2-Sided) 95%; -2.12 to 0.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.631
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.59
	Confidence Interval	(2-Sided) 95%; -2.90 to -0.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.663
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I-III)
Description	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).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	56	70	61	50
Least Squares Mean (Standard Error) [Units on a scale]	-0.18 (2.112)	-6.58 (1.941)	-7.56 (2.084)	-10.77 (2.287)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.026
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.41
	Confidence Interval	(2-Sided) 95%; -12.04 to -0.77
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.860
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-7.39
	Confidence Interval	(2-Sided) 95%; -13.24 to -1.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.969
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-10.60
	Confidence Interval	(2-Sided) 95%; -16.72 to -4.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.104
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in the Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) Total Score
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	73	77	67	55
Least Squares Mean (Standard Error) [Units on a scale]	-0.32 (0.976)	0.23 (0.961)	2.09 (1.018)	1.24 (1.128)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.683
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; -2.13 to 3.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.362
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.089
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.41
	Confidence Interval	(2-Sided) 95%; -0.37 to 5.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.413
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.294
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.56
	Confidence Interval	(2-Sided) 95%; -1.37 to 4.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.489
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test Score
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	71	76	66	53
Least Squares Mean (Standard Error) [Units on a scale]	-0.19 (0.280)	0.44 (0.271)	0.88 (0.292)	0.30 (0.325)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.105
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; -0.13 to 1.40
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.389
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.27 to 1.87
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.406
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.253
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; -0.35 to 1.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.428
	Estimation Comments

11. Secondary Outcome

Title	Change in MDS-UPDRS Parts II (Motor Experiences of Daily Living) and III (Motor Exam) From Baseline to Week 12
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	75	77	69	54
Motor Experiences of Daily Living	0.28 (0.656)	-1.45 (0.649)	-2.08 (0.700)	-3.22 (0.779)
Motor Exam	-0.12 (1.343)	-3.39 (1.240)	-3.40 (1.331)	-4.35 (1.434)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Motor Experiences of Daily Living
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.061
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.74
	Confidence Interval	(2-Sided) 95%; -3.56 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.923
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Motor Experiences of Daily Living
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.37
	Confidence Interval	(2-Sided) 95%; -4.26 to -0.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.960
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Motor Experiences of Daily Living
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.50
	Confidence Interval	(2-Sided) 95%; -5.50 to -1.51
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.013
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Motor Exam
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.074
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.27
	Confidence Interval	(2-Sided) 95%; -6.86 to 0.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.822
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Motor Exam
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.085
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.27
	Confidence Interval	(2-Sided) 95%; -7.00 to 0.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.891
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Motor Exam
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.032
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.23
	Confidence Interval	(2-Sided) 95%; -8.09 to -0.37
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.959
	Estimation Comments

12. Secondary Outcome

Title	Number of Participants Who Met the Potentially Clinically Significant Vital Signs Criteria at 3 Consecutive Time Points at Visit 3
Description	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).
Time Frame	Visit 3 (Day 1 stopping rules)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	86	86	65	87
Count of Participants [Participants]	0 0%	0 0%	1 1.2%	1 1.1%

13. Secondary Outcome

Title	Change From Baseline in Clinic Blood Pressure (BP) to 8 Hours Post Dose
Description	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.
Time Frame	Baseline, 8 Hours Post Dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	81	82	79	85
Sitting Systolic Blood Pressure	9.8 (1.90)	10.1 (1.89)	10.4 (1.92)	19.2 (1.87)
Sitting Diastolic Blood Pressure	4.6 (0.99)	4.9 (0.98)	5.5 (1.00)	8.1 (0.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Sitting Systolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.898
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -4.92 to 5.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Sitting Systolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.821
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -4.71 to 5.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Sitting Systolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	9.4
	Confidence Interval	(2-Sided) 95%; 4.11 to 14.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Sitting Diastolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.805
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -2.40 to 3.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Sitting Diastolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.513
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -1.85 to 3.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Sitting Diastolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; 0.83 to 6.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline in Pulse Rate to 8 Hours Post Dose
Description	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.
Time Frame	Baseline, 8 Hours Post Dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	81	82	79	85
Least Squares Mean (Standard Error) [beats/min]	-2.2 (0.94)	0.2 (0.95)	1.3 (0.95)	6.4 (0.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.065
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; -0.16 to 5.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; 0.93 to 6.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.7
	Confidence Interval	(2-Sided) 95%; 6.06 to 11.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Change From Baseline In-clinic BP to Week 12
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	74	77	65	56
Sitting Systolic Blood Pressure	-1.2 (1.22)	0.5 (1.19)	0.1 (1.29)	3.0 (1.38)
Sitting Diastolic Blood Pressure	-0.9 (0.71)	-1.0 (0.70)	-0.2 (0.75)	0.3 (0.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Sitting Systolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.339
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -1.72 to 4.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Sitting Systolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.486
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -2.26 to 4.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Sitting Systolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.2
	Confidence Interval	(2-Sided) 95%; 0.56 to 7.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Sitting Diastolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.935
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -2.04 to 1.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Sitting Diastolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.505
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -1.34 to 2.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Sitting Diastolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.266
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; -0.91 to 3.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Change From Baseline in Pulse Rate to Week 12
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	74	77	65	56
Least Squares Mean (Standard Error) [beats/min]	-0.2 (0.67)	0.3 (0.66)	1.5 (0.71)	2.6 (0.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.550
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -1.28 to 2.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.069
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -0.14 to 3.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; 0.89 to 4.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Change in Home Blood Pressure Measurement (HBPM), for SBP, DBP From Baseline to Week 12
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	48	51	41	41
Sitting Systolic Blood Pressure	-1.1 (2.52)	-8.2 (2.40)	2.0 (2.58)	-2.2 (2.62)
Sitting Diastolic Blood Pressure	1.5 (1.50)	-2.8 (1.45)	1.0 (1.55)	-0.8 (1.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Sitting Systolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.045
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-7.0
	Confidence Interval	(2-Sided) 95%; -13.92 to -0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Sitting Systolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.390
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; -4.05 to 10.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Sitting Systolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.768
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -8.32 to 6.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Sitting Diastolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.041
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.3
	Confidence Interval	(2-Sided) 95%; -8.48 to -0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Sitting Diastolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.802
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -4.81 to 3.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Sitting Diastolic Blood Pressure
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.284
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -6.67 to 1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Change in HBPM for Pulse Rate From Baseline to Week 12
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	48	51	41	41
Least Squares Mean (Standard Error) [beats/min]	1.4 (1.52)	1.4 (1.47)	0.7 (1.59)	0.8 (1.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.996
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -4.17 to 4.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.767
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -4.99 to 3.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.791
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -4.96 to 3.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Change From Baseline in the Physician Withdrawal Checklist (PWC)-20 Total Score From Week 12 to In-Clinic Follow-up Visit
Description	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 Mild Moderate 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.
Time Frame	Week 12, Follow-up (2 Weeks after Week 12)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	35	33	32	24
Week 12	-1.51 (0.670)	-0.53 (0.690)	-0.47 (0.701)	0.05 (0.811)
Follow-up	-1.27 (0.844)	0.12 (0.877)	0.13 (0.904)	3.32 (1.040)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.312
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; -0.93 to 2.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.289
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; -0.89 to 2.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.141
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.56
	Confidence Interval	(2-Sided) 95%; -0.53 to 3.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	10 mg LY3154207, 30 mg LY3154207
	Comments	Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.954
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -1.89 to 2.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	10 mg LY3154207, 75 mg LY3154207
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.584
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; -1.53 to 2.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	30 mg LY3154207, 75 mg LY3154207
	Comments	Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.623
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; -1.59 to 2.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 10 mg LY3154207
	Comments	Follow-up
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.256
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 95%; -1.02 to 3.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3154207
	Comments	Follow-up
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.258
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 95%; -1.04 to 3.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, 75 mg LY3154207
	Comments	Follow-up
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.59
	Confidence Interval	(2-Sided) 95%; 1.93 to 7.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	10 mg LY3154207, 30 mg LY3154207
	Comments	Follow-up
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.988
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -2.47 to 2.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	10 mg LY3154207, 75 mg LY3154207
	Comments	Follow-up
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.20
	Confidence Interval	(2-Sided) 95%; 0.51 to 5.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	30 mg LY3154207, 75 mg LY3154207
	Comments	Follow-up
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.18
	Confidence Interval	(2-Sided) 95%; 0.46 to 5.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Pharmacokinetics (PK): Steady-State Trough Plasma Concentrations of LY3154207
Description	Trough measurements of LY3154207 concentration in plasma at Day 1, Day 7, Day 14, Day 42 and Day 84 was evaluated.
Time Frame	Day 1: 1-3 hours post-dose; Day 7, Day 14 and Day 42: post-dose; Day 84: pre-dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	10 mg LY3154207	30 mg LY3154207	75 mg LY3154207
Arm/Group Description	Participants received 10 mg LY3154207 administered orally QD.	Participants received 30 mg LY3154207 administered orally QD.	Participants received 75 mg LY3154207 administered orally QD.
Measure Participants	86	77	81
Day 1	34.95 (28.82)	89.36 (88.03)	223.30 (208.63)
Day 7	50.53 (38.20)	123.61 (100.89)	297.35 (242.47)
Day 14	45.85 (33.61)	129.24 (89.24)	321.65 (253.11)
Day 42	44.25 (33.93)	149.22 (122.01)	333.40 (257.74)
Day 84	25.01 (30.43)	59.39 (58.20)	126.53 (197.67)

Adverse Events

Time Frame	Up To 4 Months
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug.
Arm/Group Title	Placebo		10 mg LY3154207		30 mg LY3154207		75 mg LY3154207
Arm/Group Description	Participants received placebo administered orally QD.		Participants received 10 mg LY3154207 administered orally QD.		Participants received 30 mg LY3154207 administered orally QD.		Participants received 75 mg LY3154207 administered orally QD.
All Cause Mortality
	Placebo		10 mg LY3154207		30 mg LY3154207		75 mg LY3154207
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/86 (0%)		0/86 (0%)		1/85 (1.2%)		1/87 (1.1%)
Serious Adverse Events
	Placebo		10 mg LY3154207		30 mg LY3154207		75 mg LY3154207
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/86 (3.5%)		5/86 (5.8%)		3/85 (3.5%)		10/87 (11.5%)
Cardiac disorders
Angina pectoris	1/86 (1.2%)	1	0/86 (0%)	0	0/85 (0%)	0	0/87 (0%)	0
Cardiac failure congestive	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Gastrointestinal disorders
Constipation	0/86 (0%)	0	1/86 (1.2%)	1	0/85 (0%)	0	0/87 (0%)	0
Oesophagitis	1/86 (1.2%)	1	0/86 (0%)	0	0/85 (0%)	0	0/87 (0%)	0
Pancreatitis	0/86 (0%)	0	0/86 (0%)	0	1/85 (1.2%)	1	0/87 (0%)	0
General disorders
Chest pain	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Death	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Infections and infestations
Cellulitis	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Herpes zoster meningoencephalitis	0/86 (0%)	0	1/86 (1.2%)	1	0/85 (0%)	0	0/87 (0%)	0
Localised infection	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Pseudomonas infection	1/86 (1.2%)	1	0/86 (0%)	0	0/85 (0%)	0	0/87 (0%)	0
Septic shock	0/86 (0%)	0	0/86 (0%)	0	1/85 (1.2%)	1	0/87 (0%)	0
Injury, poisoning and procedural complications
Fall	0/86 (0%)	0	0/86 (0%)	0	1/85 (1.2%)	1	0/87 (0%)	0
Metabolism and nutrition disorders
Hyperammonaemia	0/86 (0%)	0	1/86 (1.2%)	1	0/85 (0%)	0	0/87 (0%)	0
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/86 (0%)	0	0/86 (0%)	0	1/85 (1.2%)	1	0/87 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Nervous system disorders
Cerebrovascular accident	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Dizziness	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Facial paralysis	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Hemianaesthesia	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Hemiparesis	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	2
Hypertensive encephalopathy	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Subarachnoid haemorrhage	0/86 (0%)	0	1/86 (1.2%)	1	0/85 (0%)	0	0/87 (0%)	0
Syncope	0/86 (0%)	0	1/86 (1.2%)	1	0/85 (0%)	0	1/87 (1.1%)	1
Psychiatric disorders
Confusional state	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Disorientation	0/86 (0%)	0	1/86 (1.2%)	1	0/85 (0%)	0	0/87 (0%)	0
Renal and urinary disorders
Tubulointerstitial nephritis	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/86 (0%)	0	1/86 (1.2%)	1	0/85 (0%)	0	0/87 (0%)	0
Vascular disorders
Hypertension	0/86 (0%)	0	0/86 (0%)	0	0/85 (0%)	0	1/87 (1.1%)	1
Other (Not Including Serious) Adverse Events
	Placebo		10 mg LY3154207		30 mg LY3154207		75 mg LY3154207
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/86 (23.3%)		26/86 (30.2%)		30/85 (35.3%)		43/87 (49.4%)
Gastrointestinal disorders
Diarrhoea	1/86 (1.2%)	1	2/86 (2.3%)	2	5/85 (5.9%)	7	2/87 (2.3%)	4
Nausea	3/86 (3.5%)	5	2/86 (2.3%)	2	7/85 (8.2%)	8	8/87 (9.2%)	9
Vomiting	3/86 (3.5%)	3	0/86 (0%)	0	2/85 (2.4%)	2	7/87 (8%)	8
General disorders
Fatigue	4/86 (4.7%)	4	2/86 (2.3%)	2	1/85 (1.2%)	1	9/87 (10.3%)	9
Infections and infestations
Urinary tract infection	2/86 (2.3%)	2	5/86 (5.8%)	5	1/85 (1.2%)	1	0/87 (0%)	0
Injury, poisoning and procedural complications
Fall	4/86 (4.7%)	10	12/86 (14%)	17	6/85 (7.1%)	7	12/87 (13.8%)	16
Nervous system disorders
Dizziness	4/86 (4.7%)	4	4/86 (4.7%)	4	6/85 (7.1%)	6	9/87 (10.3%)	10
Dyskinesia	2/86 (2.3%)	2	2/86 (2.3%)	2	3/85 (3.5%)	3	5/87 (5.7%)	6
Headache	1/86 (1.2%)	1	2/86 (2.3%)	2	8/85 (9.4%)	8	7/87 (8%)	8
Psychiatric disorders
Hallucination	4/86 (4.7%)	4	2/86 (2.3%)	2	5/85 (5.9%)	5	9/87 (10.3%)	9
Insomnia	0/86 (0%)	0	4/86 (4.7%)	4	4/85 (4.7%)	4	5/87 (5.7%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.