A Study of LY3323795 in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02989389
• Collaborator: (none)
• Enrollment: 42
• Location: 1
• Arms: 6
• Actual Duration (Months): 7.3
• Patients Per Site Per Month: 5.8

Study Details

Study Description

Brief Summary

The main purpose of this study is to investigate the safety of LY3323795 and the effects it has on the body. The study drug or placebo (sugar pill) will be given by mouth to healthy participants. The study has three parts. Each participant may only enroll in one part. The study will last 14 to 43 days, depending on the part. Screening must be completed prior to study start.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: LY3323795; Drug: Itraconazole; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Single-Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3323795 in Healthy Subjects
• Actual Study Start Date: Dec 12, 2016
• Actual Primary Completion Date: Jul 21, 2017
• Actual Study Completion Date: Jul 21, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY3323795 (Part A) Participants received escalating doses of 0.3 mg (milligrams), 1 mg, 3 mg, 10 mg, 30 mg and 100 mg of LY3323795 orally.	Drug: LY3323795; Administered orally
Placebo Comparator: Placebo (Part A) Participants received placebo identical to LY3323795 orally.	Drug: Placebo; Administered orally
Experimental: LY3323795 (Part B) Participants received 6 mg, 20 mg and 80 mg of LY3323795 orally.	Drug: LY3323795; Administered orally
Placebo Comparator: Placebo (Part B) Participants received placebo identical to LY3323795 orally.	Drug: Placebo; Administered orally
Experimental: LY3323795 (Part C) Part C was not initiated due to a Lilly internal strategy decision.	Drug: LY3323795; Administered orally
Experimental: LY3323795 + Itraconazole (Part C) Part C was not initiated due to a Lilly internal strategy decision.	Drug: LY3323795; Administered orally; Drug: Itraconazole; Administered orally

Outcome Measures

Primary Outcome Measures

1. Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration [Baseline to Study Completion (up to Day 43)]

   Data presented are the number of participants who experienced 1 or more SAEs considered by the investigator to be related to study drug administration is reported. SAEs were classified using the Medical Dictionary for Regulatory Activities (MedDRA) 19.1. A summary of non-serious adverse events and all serious adverse events, regardless of causality is located in the Reported Adverse Events section.

Secondary Outcome Measures

1. Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma [0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72,96,120,144 hours, post dose]

   Pharmacokinetics (PK): Maximum observed drug concentration (Cmax) of LY3323795 in plasma.

2. Part B Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Cerebrospinal Fluid (CSF) [-4, -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36 hours, post dose]

   Part B Pharmacokinetics (PK): Maximum observed drug concentration (Cmax) of LY3323795 in cerebrospinal fluid (CSF).

3. Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma [0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72,96,120,144 hours, post dose]

   Pharmacokinetics (PK): Area under the concentration time curve from time zero to tlast (AUC[0-tlast]) of LY3323795 in plasma.

4. Part B Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Cerebrospinal Fluid (CSF) [-4, -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36 hours, post dose]

   Part B Pharmacokinetics (PK): Area under the concentration time curve from time zero to tlast (AUC[0-tlast]) of LY3323795 in cerebrospinal fluid (CSF).

5. Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ [Baseline through 144 hours]

   Amyloid beta is a peptide fragment of the amyloid precursor protein, plasma concentrations of Aβ1-40 and Aβ1-42 were determined using validated immunoassay methods.

6. Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ [Baseline through 36 hours]

   Amyloid beta is a peptide fragment of the amyloid precursor protein, CSF concentrations of Aβ1-40, Aβ1-42 were determined using validated immunoassay methods.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy males or females of non-childbearing potential at time of screening

• Have a body mass index (BMI) between 18.0 kilograms per square meter (kg/m²) and 32.0 kg/m², inclusive

Exclusion Criteria:

• Have participated, within the last 30 days, in a clinical trial involving an investigational product.

• Have a QT corrected for heart rate (QTc) (using Bazett's formula) interval value of greater than 450 millisecond (msec) (males) or greater than 470 msec (females)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Clinical Trials Medical Group	Glendale	California	United States	91260

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)

• Study Protocol - Dec 2, 2016
• Statistical Analysis Plan - Dec 20, 2016

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02989389
• Other Study ID Numbers: 16610; I9F-MC-SCAA
• First Posted: Dec 12, 2016
• Last Update Posted: Apr 20, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Itraconazole

Study Results

Participant Flow

Pre-assignment Detail	Part A was a dose-escalation 3-period crossover with 2 alternating cohorts (Cohorts 1 and 2). There was 14 days of washout time between each dose. Part B was a single-dose, 3-cohort (Cohorts 3, 4 and 5) study.

Arm/Group Title	Part A-Cohort 1 (Sequence 1)	Part A-Cohort 1 (Sequence 2)	Part A-Cohort 1 (Sequence 3)	Part A-Cohort 2 (Sequence 1)	Part A-Cohort 2 (Sequence 2)	Part A-Cohort 2 (Sequence 3)	Part B, 6 mg LY3323795	Part B, 20 mg LY3323795	Part B, 80 mg LY3323795	Part B, Placebo
Arm/Group Description	Participants received 0.3 milligrams (mg), 3 mg, 30 mg LY3323795 and Placebo. Period 1: Placebo, Period 2: 3 mg LY3323795, Period 3: 30 mg LY3323795	Participants received 0.3 mg, 3 mg, 30 mg LY3323795 and Placebo. Period 1: 0.3 mg LY3323795, Period 2: Placebo, Period 3: 30 mg LY3323795	Participants received 0.3 mg, 3 mg, 30 mg LY3323795 and Placebo. Period 1: 0.3 mg LY3323795, Period 2: 3 mg LY3323795, Period 3: Placebo	Participants received 1 mg, 10 mg, 100 mg of LY3323795 and Placebo. Period 1: 1 mg LY3323795, Period 2: 10 mg LY3323795, Period 3: Placebo	Participants received 1 mg, 10 mg, 100 mg of LY3323795 and Placebo. Period 1: Placebo, Period 2: 10 mg LY3323795, Period 3: 100 mg LY3323795	Participants received 1 mg, 10 mg, 100 mg of LY3323795 and Placebo. Period 1: 1 mg LY3323795, Period 2: Placebo, Period 3: 100 mg LY3323795	Participants received 6 mg of LY3323795 orally.	Participants received 20 mg of LY3323795 orally.	Participants received 80 mg of LY3323795 orally.	Participants received placebo identical to LY3323795 orally.
Period Title: Period 1
STARTED	3	4	3	3	3	3	6	5	6	6
Received at Least 1 Dose of Study Drug	3	4	3	3	3	3	6	5	6	6
COMPLETED	3	3	3	3	3	3	6	5	5	6
NOT COMPLETED	0	1	0	0	0	0	0	0	1	0
Period Title: Period 1
STARTED	3	3	3	3	3	3	0	0	0	0
COMPLETED	3	3	3	3	3	3	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period Title: Period 1
STARTED	3	3	3	3	3	3	0	0	0	0
COMPLETED	3	3	3	3	3	3	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part A-Cohort 1 (Sequence 1)	Part A-Cohort 1 (Sequence 2)	Part A-Cohort 1 (Sequence 3)	Part A-Cohort 2 (Sequence 1)	Part A-Cohort 2 (Sequence 2)	Part A-Cohort 2 (Sequence 3)	Part B, 6 mg LY3323795	Part B, 20 mg LY3323795	Part B, 80 mg LY3323795	Part B, Placebo	Total
Arm/Group Description	Participants received 0.3 milligrams (mg), 3 mg, 30 mg LY3323795 and Placebo. Period 1: Placebo, Period 2: 3 mg LY3323795, Period 3: 30 mg LY3323795.	Participants received 0.3 mg, 3 mg, 30 mg LY3323795 and Placebo. Period 1: 0.3 mg LY3323795, Period 2: Placebo, Period 3: 30 mg LY3323795.	Participants received 0.3 mg, 3 mg, 30 mg LY3323795 and Placebo. Period 1: 0.3 mg LY3323795, Period 2: 3 mg LY3323795, Period 3: Placebo.	Participants received 1 mg, 10 mg, 100 mg of LY3323795 and Placebo. Period 1: 1 mg LY3323795, Period 2: 10 mg LY3323795, Period 3: Placebo.	Participants received 1 mg, 10 mg, 100 mg of LY3323795 and Placebo. Period 1: Placebo, Period 2: 10 mg LY3323795, Period 3: 100 mg LY3323795.	Participants received 1 mg, 10 mg, 100 mg of LY3323795 and Placebo. Period 1: 1 mg LY3323795, Period 2: Placebo, Period 3: 100 mg LY3323795.	Participants received 6 mg of LY3323795 orally.	Participants received 20 mg of LY3323795 orally.	Participants received 80 mg of LY3323795 orally.	Participants received placebo identical to LY3323795 orally.	Total of all reporting groups
Overall Participants	3	4	3	3	3	3	6	5	6	6	42
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	4 100%	3 100%	3 100%	3 100%	3 100%	6 100%	4 80%	6 100%	6 100%	41 97.6%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 20%	0 0%	0 0%	1 2.4%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	1 33.3%	0 0%	2 66.7%	0 0%	3 50%	2 40%	1 16.7%	2 33.3%	11 26.2%
Male	3 100%	4 100%	2 66.7%	3 100%	1 33.3%	3 100%	3 50%	3 60%	5 83.3%	4 66.7%	31 73.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 66.7%	1 25%	1 33.3%	1 33.3%	1 33.3%	2 66.7%	1 16.7%	0 0%	0 0%	0 0%	9 21.4%
Not Hispanic or Latino	1 33.3%	3 75%	2 66.7%	2 66.7%	2 66.7%	1 33.3%	5 83.3%	5 100%	6 100%	5 83.3%	32 76.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	1 2.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 20%	1 16.7%	1 16.7%	3 7.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 25%	1 33.3%	1 33.3%	1 33.3%	1 33.3%	1 16.7%	1 20%	2 33.3%	1 16.7%	10 23.8%
White	3 100%	1 25%	2 66.7%	2 66.7%	2 66.7%	2 66.7%	5 83.3%	3 60%	3 50%	3 50%	26 61.9%
More than one race	0 0%	2 50%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	3 7.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	3 100%	4 100%	3 100%	3 100%	3 100%	3 100%	6 100%	5 100%	6 100%	6 100%	42 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Description	Data presented are the number of participants who experienced 1 or more SAEs considered by the investigator to be related to study drug administration is reported. SAEs were classified using the Medical Dictionary for Regulatory Activities (MedDRA) 19.1. A summary of non-serious adverse events and all serious adverse events, regardless of causality is located in the Reported Adverse Events section.
Time Frame	Baseline to Study Completion (up to Day 43)

Outcome Measure Data

Analysis Population Description

All randomized participants who received study drug.

Arm/Group Title	Part A, Cohort 1, Placebo	Part A, Cohort 1, 0.3 mg LY3323795	Part A, Cohort 1, 3 mg LY3323795	Part A, Cohort 1, 30 mg LY3323795	Part A, Cohort 2, Placebo	Part A, Cohort 2, 1 mg LY3323795	Part A, Cohort 2, 10 mg LY3323795	Part A, Cohort 2, 100 mg LY3323795	Part B, Placebo	Part B, 6 mg LY3323795	Part B, 20 mg LY3323795	Part B, 80 mg LY3323795
Arm/Group Description	Participants received placebo identical to LY3323795 orally.	Participants received 0.3 mg of LY3323795 orally.	Participants received 3 mg of LY3323795 orally.	Participants received 30 mg of LY3323795 orally.	Participants received placebo identical to LY3323795 orally.	Participants received 1 mg of LY3323795 orally.	Participants received 10 mg of LY3323795 orally.	Participants received 100 mg of LY3323795 orally.	Participants received placebo identical to LY3323795 orally.	Participants received 6 mg of LY3323795 orally.	Participants received 20 mg of LY3323795 orally.	Participants received 80 mg of LY3323795 orally.
Measure Participants	9	6	6	6	9	6	6	6	6	6	5	6
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN

2. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma
Description	Pharmacokinetics (PK): Maximum observed drug concentration (Cmax) of LY3323795 in plasma.
Time Frame	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72,96,120,144 hours, post dose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable PK data.

Arm/Group Title	Part A, Cohort 1, 0.3 mg LY3323795	Part A, Cohort 2, 1 mg LY3323795	Part A, Cohort 1, 3 mg LY3323795	Part A, Cohort 2, 10 mg LY3323795	Part A, Cohort 1, 30 mg LY3323795	Part A, Cohort 2, 100 mg LY3323795	Part B, 6 mg LY3323795	Part B, 20 mg LY3323795	Part B, 80 mg LY3323795
Arm/Group Description	Participants received 0.3 mg of LY3323795 orally.	Participants received 1 mg of LY3323795 orally.	Participants received 3 mg of LY3323795 orally.	Participants received 10 mg of LY3323795 orally.	Participants received 30 mg of LY3323795 orally.	Participants received 100 mg of LY3323795 orally.	Participants received 6 mg of LY3323795 orally.	Participants received 20 mg of LY3323795 orally.	Participants received 80 mg of LY3323795 orally.
Measure Participants	6	6	6	6	6	6	6	5	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	0.503 (32)	1.77 (29)	4.79 (24)	15.7 (25)	34.6 (35)	89.1 (44)	10.4 (45)	27.2 (26)	88.1 (34)

3. Secondary Outcome

Title	Part B Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Cerebrospinal Fluid (CSF)
Description	Part B Pharmacokinetics (PK): Maximum observed drug concentration (Cmax) of LY3323795 in cerebrospinal fluid (CSF).
Time Frame	-4, -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36 hours, post dose

Outcome Measure Data

Analysis Population Description

All randomized participants from Part B group, who received at least 1 dose of study drug and had evaluable PK data.

Arm/Group Title	Part B, 6 mg LY3323795	Part B, 20 mg LY3323795	Part B, 80 mg LY3323795
Arm/Group Description	Participants received 6 mg of LY3323795 orally.	Participants received 20 mg of LY3323795 orally.	Participants received 80 mg of LY3323795 orally.
Measure Participants	6	5	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	0.293 (31)	0.788 (11)	2.86 (34)

4. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma
Description	Pharmacokinetics (PK): Area under the concentration time curve from time zero to tlast (AUC[0-tlast]) of LY3323795 in plasma.
Time Frame	0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72,96,120,144 hours, post dose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable PK data.

Arm/Group Title	Part A, Cohort 1, 0.3 mg LY3323795	Part A, Cohort 2, 1 mg LY3323795	Part A, Cohort 1, 3 mg LY3323795	Part A, Cohort 2, 10 mg LY3323795	Part A, Cohort 1, 30 mg LY3323795	Part A, Cohort 2, 100 mg LY3323795	Part B, 6 mg LY3323795	Part B, 20 mg LY3323795	Part B, 80 mg LY3323795
Arm/Group Description	Participants received 0.3 mg of LY3323795 orally.	Participants received 1 mg of LY3323795 orally.	Participants received 3 mg of LY3323795 orally.	Participants received 10 mg of LY3323795 orally.	Participants received 10 mg of LY3323795 orally.	Participants received 100 mg of LY3323795 orally.	Participants received 6 mg of LY3323795 orally.	Participants received 20 mg of LY3323795 orally.	Participants received 80 mg of LY3323795 orally.
Measure Participants	6	6	6	6	6	6	6	7	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*h/mL)]	5.67 (69)	25.2 (28)	73.4 (31)	274 (14)	663 (35)	2370 (29)	156 (17)	441 (24)	1950 (49)

5. Secondary Outcome

Title	Part B Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Cerebrospinal Fluid (CSF)
Description	Part B Pharmacokinetics (PK): Area under the concentration time curve from time zero to tlast (AUC[0-tlast]) of LY3323795 in cerebrospinal fluid (CSF).
Time Frame	-4, -2, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36 hours, post dose

Outcome Measure Data

Analysis Population Description

All randomized participants from Part B group, who received at least 1 dose of study drug and had evaluable PK data.

Arm/Group Title	Part B, 6 mg LY3323795	Part B, 20 mg LY3323795	Part B, 80 mg LY3323795
Arm/Group Description	Participants received 6 mg of LY3323795 orally.	Participants received 20 mg of LY3323795 orally.	Participants received 80 mg of LY3323795 orally.
Measure Participants	6	5	6
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	5.46 (24)	13.7 (16)	55.1 (48)

6. Secondary Outcome

Title	Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂
Description	Amyloid beta is a peptide fragment of the amyloid precursor protein, plasma concentrations of Aβ1-40 and Aβ1-42 were determined using validated immunoassay methods.
Time Frame	Baseline through 144 hours

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and have baseline and at least one post-baseline plasma Aβ1-40 or Aβ1-42 data.

Arm/Group Title	Part A, Cohort 1, 0.3 mg LY3323795	Part A, Cohort 2, 1 mg LY3323795	Part A, Cohort 1, 3 mg LY3323795	Part A, Cohort 2, 10 mg LY3323795	Part A, Cohort 1, 30 mg LY3323795	Part A, Cohort 2, 100 mg LY3323795	Part B, 6 mg LY3323795	Part B, 20 mg LY3323795	Part B, 80 mg LY3323795	Placebo
Arm/Group Description	Participants received 0.3 mg of LY3323795 orally.	Participants received 1 mg of LY3323795 orally.	Participants received 3 mg of LY3323795 orally.	Participants received 10 mg of LY3323795 orally.	Participants received 30 mg of LY3323795 orally.	Participants received 100 mg of LY3323795 orally.	Participants received 6 mg of LY3323795 orally.	Participants received 20 mg of LY3323795 orally.	Participants received 80 mg of LY3323795 orally.	Participants received placebo identical to LY3323795 orally.
Measure Participants	6	6	6	6	6	6	6	5	5	24
Aβ1-40	-39 (8)	-52 (6)	-71 (7)	-76 (4)	-76 (18)	-89 (2)	-79 (7)	-81 (5)	-89 (1)	-23 (11)
Aβ1-42	-22 (7)	-33 (6)	-49 (5)	-60 (5)	-63 (8)	-75 (3)	-54 (11)	-58 (6)	-64 (9)	-12 (6)

7. Secondary Outcome

Title	Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂
Description	Amyloid beta is a peptide fragment of the amyloid precursor protein, CSF concentrations of Aβ1-40, Aβ1-42 were determined using validated immunoassay methods.
Time Frame	Baseline through 36 hours

Outcome Measure Data

Analysis Population Description

All randomized participants from Part B group, who received at least 1 dose of study drug and have baseline and at least one post-baseline CSF Aβ1-40 or Aβ1-42 data.

Arm/Group Title	Part B, 6 mg LY3323795	Part B, 20 mg LY3323795	Part B, 80 mg LY3323795	Placebo
Arm/Group Description	Participants received 6 mg of LY3323795 orally.	Participants received 20 mg of LY3323795 orally.	Participants received 80 mg of LY3323795 orally.	Participants received placebo identical to LY3323795 orally.
Measure Participants	6	5	4	6
Aβ 1-40	-51 (21)	-69 (6)	-88 (4)	-12 (11)
Aβ 1-42	-37 (23)	-71 (10)	-81 (7)	-17 (23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohort 1, Placebo, Part A, Cohort 1, 30 mg LY3323795
	Comments	Aβ 1-40
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.215
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-11.57
	Confidence Interval	(2-Sided) 90%; -29.52 to 10.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohort 1, 0.3 mg LY3323795, Part A, Cohort 1, 30 mg LY3323795
	Comments	Aβ 1-40
	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 (Final Values)
	Estimated Value	-60.53
	Confidence Interval	(2-Sided) 90%; -69.79 to -48.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohort 1, 3 mg LY3323795, Part A, Cohort 1, 30 mg LY3323795
	Comments	Aβ 1-40
	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 (Final Values)
	Estimated Value	-87.07
	Confidence Interval	(2-Sided) 90%; -90.21 to -82.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohort 1, Placebo, Part A, Cohort 1, 30 mg LY3323795
	Comments	Aβ 1-42
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-19.60
	Confidence Interval	(2-Sided) 90%; -33.69 to -2.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohort 1, 0.3 mg LY3323795, Part A, Cohort 1, 30 mg LY3323795
	Comments	Aβ 1-42
	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 (Final Values)
	Estimated Value	-65.41
	Confidence Interval	(2-Sided) 90%; -72.23 to -56.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Part A, Cohort 1, 3 mg LY3323795, Part A, Cohort 1, 30 mg LY3323795
	Comments	Aβ 1-42
	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 (Final Values)
	Estimated Value	-84.56
	Confidence Interval	(2-Sided) 90%; -88.97 to -78.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Up to 43 days
Adverse Event Reporting Description	All enrolled participants who received study drug.
Arm/Group Title	Part A, Cohort 1, Placebo		Part A, Cohort 1, 0.3 mg LY3323795		Part A, Cohort 1, 3 mg LY3323795		Part A, Cohort 1, 30 mg LY3323795		Part A, Cohort 2, Placebo		Part A, Cohort 2, 1 mg LY3323795		Part A, Cohort 2, 10 mg LY3323795		Part A, Cohort 2, 100 mg LY3323795		Part B, 6 mg LY3323795		Part B, 20 mg LY3323795		Part B, 80 mg LY3323795		Part B, Placebo
Arm/Group Description	Participants received placebo identical to LY3323795 orally.		Participants received 0.3 mg of LY3323795 orally.		Participants received 3 mg of LY3323795 orally.		Participants received 30 mg of LY3323795 orally.		Participants received placebo identical to LY3323795 orally.		Participants received 1 mg of LY3323795 orally.		Participants received 10 mg of LY3323795 orally.		Participants received 100 mg of LY3323795 orally.		Participants received 6 mg of LY3323795 orally.		Participants received 20 mg of LY3323795 orally.		Participants received 80 mg of LY3323795 orally.		Participants received placebo identical to LY3323795 orally.
All Cause Mortality
	Part A, Cohort 1, Placebo		Part A, Cohort 1, 0.3 mg LY3323795		Part A, Cohort 1, 3 mg LY3323795		Part A, Cohort 1, 30 mg LY3323795		Part A, Cohort 2, Placebo		Part A, Cohort 2, 1 mg LY3323795		Part A, Cohort 2, 10 mg LY3323795		Part A, Cohort 2, 100 mg LY3323795		Part B, 6 mg LY3323795		Part B, 20 mg LY3323795		Part B, 80 mg LY3323795		Part B, Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Part A, Cohort 1, Placebo		Part A, Cohort 1, 0.3 mg LY3323795		Part A, Cohort 1, 3 mg LY3323795		Part A, Cohort 1, 30 mg LY3323795		Part A, Cohort 2, Placebo		Part A, Cohort 2, 1 mg LY3323795		Part A, Cohort 2, 10 mg LY3323795		Part A, Cohort 2, 100 mg LY3323795		Part B, 6 mg LY3323795		Part B, 20 mg LY3323795		Part B, 80 mg LY3323795		Part B, Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Part A, Cohort 1, Placebo		Part A, Cohort 1, 0.3 mg LY3323795		Part A, Cohort 1, 3 mg LY3323795		Part A, Cohort 1, 30 mg LY3323795		Part A, Cohort 2, Placebo		Part A, Cohort 2, 1 mg LY3323795		Part A, Cohort 2, 10 mg LY3323795		Part A, Cohort 2, 100 mg LY3323795		Part B, 6 mg LY3323795		Part B, 20 mg LY3323795		Part B, 80 mg LY3323795		Part B, Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)		1/9 (11.1%)		1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)		5/6 (83.3%)		3/5 (60%)		6/6 (100%)		3/6 (50%)
Eye disorders
Vision blurred	0/9 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Abdominal pain	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Constipation	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Diarrhoea haemorrhagic	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Nausea	0/9 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Vomiting	0/9 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/5 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
General disorders
Catheter site pain	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/5 (20%)	1	0/6 (0%)	0	0/6 (0%)	0
Fatigue	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Vessel puncture site bruise	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/5 (20%)	1	0/6 (0%)	0	0/6 (0%)	0
Infections and infestations
Nasopharyngitis	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Injury, poisoning and procedural complications
Laceration	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Post lumbar puncture syndrome	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	1/5 (20%)	1	3/6 (50%)	3	2/6 (33.3%)	2
Procedural complication	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	2	0/6 (0%)	0
Procedural headache	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Procedural nausea	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Procedural pain	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/5 (0%)	0	2/6 (33.3%)	4	1/6 (16.7%)	2
Procedural vomiting	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Back pain	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Groin pain	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Musculoskeletal stiffness	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Neck pain	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Nervous system disorders
Headache	0/9 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Nasal congestion	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/5 (0%)	0	0/6 (0%)	0	0/6 (0%)	0

Limitations/Caveats

Part C (an itraconazole interaction study) was not initiated due to a Lilly internal strategy decision.

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.