Study of LY2886721 in Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01561430
• Collaborator: (none)
• Enrollment: 70
• Locations: 34
• Arms: 4
• Duration (Months): 17
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this Phase 1/Phase 2 study is to evaluate how the body handles the drug and the drug's effect on the body of participants with mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or mild AD and who test positive for amyloid plaque.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: LY2886721; Drug: Placebo	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: Assessment of Safety, Tolerability, and Pharmacodynamic Effects of LY2886721 in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 15 mg LY2886721 LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.	Drug: LY2886721
Experimental: 35 mg LY2886721 LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.	Drug: LY2886721
Experimental: 70 mg LY2886721 LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.	Drug: LY2886721
Placebo Comparator: Placebo Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations [Baseline, 12 weeks]

   Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 12 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect.

2. Change From Baseline to 26 Weeks in CSF Aβ1-40 and Aβ1-42 Concentrations [Baseline, 26 weeks]

   Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 26 weeks post-dose was to be calculated. The units for CSF were picograms per milliliter (pg/mL). LS means of percent change in concentration from baseline was calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect.

Secondary Outcome Measures

1. Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations [Baseline, 12 weeks, 26 weeks]

   Percent change in plasma concentrations of Aβ1-40 and Aβ1-42 from baseline at 12 weeks and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL).

2. Change From Baseline to 26 Weeks in Neuropsychological Test Battery (NTB) [Baseline, 26 weeks]

   The NTB is a composite cognitive measure in clinical Alzheimer's disease studies and is a collection of several written and oral tests that examines verbal and nonverbal brain functions. NTB Z-score typically ranges from -3 to 3, with lower scores suggesting greater cognitive impairment. LS means were calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect.

3. Change From Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) [Baseline, 26 weeks]

   ADAS-Cog11 is an 11-item instrument measuring impairment in memory (Items 1-4, 7, 11), praxis (Items 4 and 5), orientation (Item 6), and language (Items 8-10). Item 1 ranged 0 (all items recalled correctly)-10 (none recalled correctly); Items 2-5 and 8-11 ranged 0 (all items named, performed, drawn, spoken, remember correctly/clearly)-5 (none correct/not clearly spoken); Item 6 ranged 0 (no incorrect responses)-8 (all incorrect); and Item 7 ranged 0 (all words remembered correctly)-12 (no words remembered correctly) for a total ADAS-Cog11 score of 0-70 with higher scores indicating greater disease severity. A score of 0-10 for delayed free recall and a conversion code of 0-5 for digit cancellation and maze completion was added to the total ADAS-Cog11 score for a total ADAS-Cog14 score ranging 0-90 with higher scores indicating greater impairment. LS means were calculated using Mixed Model Repeated Measures (MMRM) with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit.

4. Change From Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) [Baseline, 26 weeks]

   The CDR-SB is a composite measure of 6 domains of cognitive and functional performance: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Scores ranged from 0 to 18, with higher scores indicating greater impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit.

5. Change From Baseline to 26 Weeks in Mini Mental State Examination (MMSE) [Baseline, 26 weeks]

   The MMSE (Folstein et al. 1975) is one of the most widely used screening instruments for cognitive impairment. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and provides a total score ranging from 0 to 30, with lower scores indicative of greater cognitive impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit.

6. Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations [Baseline, 12 weeks, 26 weeks]

   Percent change in lumbar CSF tau and ptau-181 concentrations from baseline at 12 weeks post-dose and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Meets criteria for MCI due to AD or Mild AD

All participants will be required to undergo assessment via the Mini Mental State Examination (MMSE) scale at screening

• Participants with MMSE scores of 20 to 26, inclusive, may be enrolled provided they meet the criteria for mild AD, as follows:

• Participant meets the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD

• Clinical Dementia Rating Scale (CDR) score of 0.5 or 1

• Positive scan for the presence of amyloid beta

• Participants with MMSE of 27 to 30, inclusive, may be enrolled as participants with

MCI due to AD provided they meet the following criteria:

• Gradual and progressive change in memory function as reported by the participant or a caregiver during a period of more than 6 months

• Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR): free recall ≤22 and total recall ≤46

• Absence of dementia

• Preservation of functional independence

• Exclusion of other potential (vascular, traumatic, or medical) causes of cognitive decline, where possible

• Positive scan for the presence of amyloid beta

• Women must be postmenopausal

• Men are required to use an approved barrier method of contraception if their partners are pregnant, or of childbearing potential and not using approved contraceptive methods

Exclusion Criteria:

• Participant in another drug or device study

• Have a history of frontotemporal dementia, Lewy body disease, vascular dementia, Huntington's disease, Parkinson's disease, progressive supranuclear palsy (PSNP), or other movement disorder

• Participants are not on a stable standard of care (acetylcholinesterase inhibitors, memantine) initiated less than 2 months prior to entry or have less than 4 weeks of stable therapy. Note: Stable standard of care is allowed.

• Have had a serious infectious disease affecting the brain in the past 5 years

• Have had a serious or repeat head injury

• Have significant retinal impairment or disease

• Have had a stroke or other circulation problems that are affecting current health

• Have had a seizure

• Have major depressive disorder and are not on a stable dose of medication. Participants who no longer meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV) criteria for major depression may be included

• History of schizophrenia, bipolar disorder, or severe mental illness

• History of alcohol or drug abuse

• Have asthma, chronic obstructive pulmonary disease (COPD), or other breathing disease that is not controlled with medicine

• Have human immunodeficiency virus (HIV) or syphilis

• Are taking blood thinners

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Phoenix	Arizona	United States	85006
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sun City	Arizona	United States	85351
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tucson	Arizona	United States	85741
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Long Beach	California	United States	90806
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	San Francisco	California	United States	94109
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Denver	Colorado	United States	80239
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New Haven	Connecticut	United States	06510
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Boca Raton	Florida	United States	33486
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Delray Beach	Florida	United States	33445
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fort Myers	Florida	United States	33912
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ocala	Florida	United States	34471
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Orlando	Florida	United States	32806
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	West Palm Beach	Florida	United States	33407
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Decatur	Georgia	United States	30033
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chicago	Illinois	United States	60612
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lexington	Kentucky	United States	40504
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Plymouth	Massachusetts	United States	02360
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Quincy	Massachusetts	United States	02169
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Monroe	New Jersey	United States	08831
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Albany	New York	United States	12206
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Durham	North Carolina	United States	27705
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dayton	Ohio	United States	45408
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Portland	Oregon	United States	97210
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Salt Lake City	Utah	United States	84106
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Biella		Italy	13900
26	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pisa		Italy	56126
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rome		Italy	00179
28	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka		Japan	545-8586
29	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tokyo		Japan	113
30	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Amsterdam		Netherlands	1081 GM
31	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Barcelona		Spain	08014
32	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Getafe		Spain	28905
33	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madrid		Spain	28040
34	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sant Cugal Del Valles		Spain	08195

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (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)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01561430
• Other Study ID Numbers: 13735; I4O-MC-BACC; 2011-005217-37
• First Posted: Mar 23, 2012
• Last Update Posted: May 18, 2018
• Last Verified: May 1, 2018

• Keywords provided by Eli Lilly and Company: beta-secretase inhibitor
• Additional relevant MeSH terms: Alzheimer Disease; Cognitive Dysfunction

Study Results

Participant Flow

Pre-assignment Detail	As a result of findings from the I4O-MC-BACJ study (NCT01534273), enrollment was discontinued to the 15 milligrams (mg) arm. The 9 participants already enrolled were allowed to continue study treatment at the 15 mg dose.

Arm/Group Title	15 mg LY2886721	35 mg LY2886721	70 mg LY2886721	Placebo
Arm/Group Description	LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.	LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.	LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.	Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.
Period Title: Overall Study
STARTED	9	23	18	20
Received at Least One Dose of Study Drug	9	23	18	20
COMPLETED	8	8	1	7
NOT COMPLETED	1	15	17	13

Baseline Characteristics

Arm/Group Title	15 mg LY2886721	35 mg LY2886721	70 mg LY2886721	Placebo	Total
Arm/Group Description	LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.	LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.	LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.	Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.	Total of all reporting groups
Overall Participants	9	23	18	20	70
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.59 (7.569)	72.50 (8.378)	70.23 (8.603)	67.73 (7.126)	69.66 (8.201)
Sex: Female, Male (Count of Participants)
Female	5 55.6%	10 43.5%	7 38.9%	11 55%	33 47.1%
Male	4 44.4%	13 56.5%	11 61.1%	9 45%	37 52.9%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	3 13%	3 16.7%	0 0%	6 8.6%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
White	9 100%	20 87%	15 83.3%	20 100%	64 91.4%
Region of Enrollment (Count of Participants)
United States	8 88.9%	19 82.6%	15 83.3%	18 90%	60 85.7%
Netherlands	1 11.1%	1 4.3%	1 5.6%	2 10%	5 7.1%
Japan	0 0%	3 13%	2 11.1%	0 0%	5 7.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations
Description	Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 12 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with evaluable post-baseline CSF Aβ1-40 or Aβ1-42 data.

Arm/Group Title	15 mg LY2886721	35 mg LY2886721	70 mg LY2886721	Placebo
Arm/Group Description	LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.	LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.	LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.	Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.
Measure Participants	7	9	5	12
Aβ1-40	-31.8 (7.35)	-57.7 (6.67)	-58.9 (8.73)	3.7 (5.96)
Aβ1-42	-34.4 (7.27)	-52.0 (6.80)	-60.7 (8.42)	6.5 (6.06)

2. Primary Outcome

Title	Change From Baseline to 26 Weeks in CSF Aβ1-40 and Aβ1-42 Concentrations
Description	Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 26 weeks post-dose was to be calculated. The units for CSF were picograms per milliliter (pg/mL). LS means of percent change in concentration from baseline was calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect.
Time Frame	Baseline, 26 weeks

Outcome Measure Data

Analysis Population Description

Zero participants analyzed. CSF Aβ1-40 and Aβ1-42 concentrations data was not collected for analysis at 26 weeks.

Arm/Group Title	15 mg LY2886721	35 mg LY2886721	70 mg LY2886721	Placebo
Arm/Group Description	LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.	LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.	LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.	Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.
Measure Participants	0	0	0	0

3. Secondary Outcome

Title	Change From Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations
Description	Percent change in plasma concentrations of Aβ1-40 and Aβ1-42 from baseline at 12 weeks and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL).
Time Frame	Baseline, 12 weeks, 26 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with evaluable post-baseline CSF Aβ1-40 or Aβ1-42 data.

Arm/Group Title	15 mg LY2886721	35 mg LY2886721	70 mg LY2886721	Placebo
Arm/Group Description	LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.	LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.	LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.	Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.
Measure Participants	6	8	4	12
Aβ1-40, Week 12	-73.4 (6.22)	-80.8 (8.07)	-88.1 (2.66)	1.90 (15.0)
Aβ1-40, Week 26	-72.3 (11.5)	-85.0 (3.89)	-89.1 (NA)	0.944 (22.6)
Aβ1-42, Week 12	-63.4 (6.11)	-71.1 (8.38)	-78.2 (5.08)	0.541 (10.1)
Aβ1-42, Week 26	-65.1 (8.85)	-75.0 (4.33)	-80.8 (NA)	1.82 (9.98)

4. Secondary Outcome

Title	Change From Baseline to 26 Weeks in Neuropsychological Test Battery (NTB)
Description	The NTB is a composite cognitive measure in clinical Alzheimer's disease studies and is a collection of several written and oral tests that examines verbal and nonverbal brain functions. NTB Z-score typically ranges from -3 to 3, with lower scores suggesting greater cognitive impairment. LS means were calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect.
Time Frame	Baseline, 26 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with evaluable NTB data.

Arm/Group Title	15 mg LY2886721	35 mg LY2886721	70 mg LY2886721	Placebo
Arm/Group Description	LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.	LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.	LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.	Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.
Measure Participants	8	7	1	9
Least Squares Mean (Standard Error) [units on a scale]	-0.039 (0.1096)	-0.161 (0.1165)	0.424 (0.3156)	-0.262 (0.1028)

5. Secondary Outcome

Title	Change From Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)
Description	ADAS-Cog11 is an 11-item instrument measuring impairment in memory (Items 1-4, 7, 11), praxis (Items 4 and 5), orientation (Item 6), and language (Items 8-10). Item 1 ranged 0 (all items recalled correctly)-10 (none recalled correctly); Items 2-5 and 8-11 ranged 0 (all items named, performed, drawn, spoken, remember correctly/clearly)-5 (none correct/not clearly spoken); Item 6 ranged 0 (no incorrect responses)-8 (all incorrect); and Item 7 ranged 0 (all words remembered correctly)-12 (no words remembered correctly) for a total ADAS-Cog11 score of 0-70 with higher scores indicating greater disease severity. A score of 0-10 for delayed free recall and a conversion code of 0-5 for digit cancellation and maze completion was added to the total ADAS-Cog11 score for a total ADAS-Cog14 score ranging 0-90 with higher scores indicating greater impairment. LS means were calculated using Mixed Model Repeated Measures (MMRM) with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit.
Time Frame	Baseline, 26 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with evaluable ADAS-Cog data.

Arm/Group Title	15 mg LY2886721	35 mg LY2886721	70 mg LY2886721	Placebo
Arm/Group Description	LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.	LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.	LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.	Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.
Measure Participants	7	9	1	9
Least Squares Mean (Standard Error) [units on a scale]	1.1 (2.77)	0.6 (2.48)	0.6 (7.41)	1.3 (2.44)

6. Secondary Outcome

Title	Change From Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)
Description	The CDR-SB is a composite measure of 6 domains of cognitive and functional performance: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Scores ranged from 0 to 18, with higher scores indicating greater impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit.
Time Frame	Baseline, 26 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with evaluable CDR-SB data.

Arm/Group Title	15 mg LY2886721	35 mg LY2886721	70 mg LY2886721	Placebo
Arm/Group Description	LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.	LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.	LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.	Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.
Measure Participants	8	9	1	8
Least Squares Mean (Standard Error) [units on a scale]	0.80 (0.432)	0.52 (0.395)	1.50 (1.013)	1.19 (0.402)

7. Secondary Outcome

Title	Change From Baseline to 26 Weeks in Mini Mental State Examination (MMSE)
Description	The MMSE (Folstein et al. 1975) is one of the most widely used screening instruments for cognitive impairment. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and provides a total score ranging from 0 to 30, with lower scores indicative of greater cognitive impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit.
Time Frame	Baseline, 26 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants with evaluable MMSE data.

Arm/Group Title	15 mg LY2886721	35 mg LY2886721	70 mg LY2886721	Placebo
Arm/Group Description	LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.	LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.	70 mg, capsules, administered orally, once daily for 26 weeks.	Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.
Measure Participants	8	9	1	10
Least Squares Mean (Standard Error) [units on a scale]	-0.7 (0.87)	-1.8 (0.81)	0.2 (2.41)	-3.0 (0.77)

8. Secondary Outcome

Title	Change From Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations
Description	Percent change in lumbar CSF tau and ptau-181 concentrations from baseline at 12 weeks post-dose and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect.
Time Frame	Baseline, 12 weeks, 26 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants at 12 weeks with evaluable post-baseline CSF Tau or Ptau data. Zero participants analyzed for 26 week CSF Tau or Ptau as data was not collected for analysis.

Arm/Group Title	15 mg LY2886721	35 mg LY2886721	70 mg LY2886721	Placebo
Arm/Group Description	LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.	LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.	LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.	Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.
Measure Participants	7	9	5	12
CSF Tau, Week 12	14.3 (6.06)	2.6 (5.42)	6.8 (7.49)	-4.4 (4.63)
CSF Ptau, Week 12	0.7 (4.81)	1.7 (4.01)	4.3 (5.41)	-3.6 (3.40)

Adverse Events

Arm/Group Title	15 mg LY2886721		35 mg LY2886721		70 mg LY2886721		Placebo
Arm/Group Description	LY2886721: 15 mg, capsules, administered orally, once daily for 26 weeks.		LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.		LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.		Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.
All Cause Mortality
	15 mg LY2886721		35 mg LY2886721		70 mg LY2886721		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	15 mg LY2886721		35 mg LY2886721		70 mg LY2886721		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		2/23 (8.7%)		0/18 (0%)		0/20 (0%)
Gastrointestinal disorders
Crohn's disease	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Small intestinal obstruction	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Nervous system disorders
Syncope	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	15 mg LY2886721		35 mg LY2886721		70 mg LY2886721		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/9 (88.9%)		13/23 (56.5%)		16/18 (88.9%)		15/20 (75%)
Blood and lymphatic system disorders
Anaemia	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Leukocytosis	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Cardiac disorders
Atrial fibrillation	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Bradycardia	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Ear and labyrinth disorders
Vertigo	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Endocrine disorders
Hypothyroidism	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Eye disorders
Cataract nuclear	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Diplopia	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Eye irritation	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Lacrimation increased	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Visual acuity reduced	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	0/9 (0%)	0	1/23 (4.3%)	2	0/18 (0%)	0	0/20 (0%)	0
Abdominal distension	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Abdominal pain upper	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Abdominal tenderness	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Dental caries	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Diarrhoea	0/9 (0%)	0	1/23 (4.3%)	1	1/18 (5.6%)	1	1/20 (5%)	1
Diverticulum intestinal	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	2
Dry mouth	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Flatulence	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Gastritis erosive	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Gastrointestinal disorder	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	2
Gastrooesophageal reflux disease	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Haematochezia	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Haemorrhoidal haemorrhage	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Haemorrhoids	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Hiatus hernia	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Lip swelling	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Nausea	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Oesophageal disorder	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Oesophagitis	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Small intestinal obstruction	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Vomiting	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	2/20 (10%)	2
General disorders
Asthenia	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Fatigue	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Oedema peripheral	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Pyrexia	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Thirst	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Hepatobiliary disorders
Hepatic function abnormal	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Infections and infestations
Herpes zoster	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Nasopharyngitis	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Sinusitis	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Upper respiratory tract infection	1/9 (11.1%)	1	1/23 (4.3%)	1	1/18 (5.6%)	1	1/20 (5%)	1
Urinary tract infection	1/9 (11.1%)	1	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Alcohol poisoning	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Contusion	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Fall	0/9 (0%)	0	1/23 (4.3%)	1	2/18 (11.1%)	3	1/20 (5%)	1
Feeding tube complication	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Foot fracture	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Joint injury	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Laceration	0/9 (0%)	0	0/23 (0%)	0	2/18 (11.1%)	3	1/20 (5%)	1
Tooth fracture	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Investigations
Alanine aminotransferase increased	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Amylase increased	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Blood alkaline phosphatase increased	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Blood creatine phosphokinase increased	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	2/20 (10%)	2
Blood pressure increased	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Colour vision tests abnormal red-green	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Electrocardiogram change	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Gamma-glutamyltransferase increased	1/9 (11.1%)	1	0/23 (0%)	0	3/18 (16.7%)	3	0/20 (0%)	0
Lipase increased	0/9 (0%)	0	1/23 (4.3%)	1	1/18 (5.6%)	2	0/20 (0%)	0
Liver function test abnormal	1/9 (11.1%)	1	2/23 (8.7%)	2	1/18 (5.6%)	1	0/20 (0%)	0
Weight increased	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Dehydration	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Hypokalaemia	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Increased appetite	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Back pain	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	2	1/20 (5%)	1
Joint range of motion decreased	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Joint swelling	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Muscle spasms	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	2/20 (10%)	2
Muscle tightness	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Musculoskeletal chest pain	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	2
Musculoskeletal stiffness	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Squamous cell carcinoma of skin	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Nervous system disorders
Apraxia	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Balance disorder	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Cerebral microhaemorrhage	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Decreased vibratory sense	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Dizziness	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Dysgeusia	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Headache	2/9 (22.2%)	2	1/23 (4.3%)	1	1/18 (5.6%)	1	0/20 (0%)	0
Sinus headache	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	4	0/20 (0%)	0
Psychiatric disorders
Abnormal dreams	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Agitation	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Anxiety	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Confusional state	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	1/20 (5%)	1
Delusion	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	1/20 (5%)	1
Depression	0/9 (0%)	0	0/23 (0%)	0	3/18 (16.7%)	3	0/20 (0%)	0
Disorientation	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Hallucination	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Hallucination, visual	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Hypnopompic hallucination	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Initial insomnia	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Insomnia	1/9 (11.1%)	1	1/23 (4.3%)	2	0/18 (0%)	0	1/20 (5%)	1
Nightmare	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Obsessive thoughts	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Parasomnia	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Restlessness	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Sleep talking	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Stereotypy	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Terminal insomnia	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Renal and urinary disorders
Cystitis interstitial	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Pollakiuria	1/9 (11.1%)	1	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Renal failure chronic	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Skin and subcutaneous tissue disorders
Actinic keratosis	1/9 (11.1%)	2	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Eczema	0/9 (0%)	0	1/23 (4.3%)	1	0/18 (0%)	0	0/20 (0%)	0
Rash	0/9 (0%)	0	0/23 (0%)	0	1/18 (5.6%)	1	0/20 (0%)	0
Rash macular	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0
Rash vesicular	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Urticaria	0/9 (0%)	0	0/23 (0%)	0	0/18 (0%)	0	1/20 (5%)	1
Vascular disorders
Hypertension	1/9 (11.1%)	1	0/23 (0%)	0	0/18 (0%)	0	0/20 (0%)	0

Limitations/Caveats

Study was terminated early because of abnormal liver biochemical tests levels for 4 participants.

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.