Healthy
Conditions
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.
Interventions
DRUGLY3323795
Administered orally
DRUGItraconazole
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Part A-Cohort 1 (Sequence 1) 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. | 3 |
| Part A-Cohort 1 (Sequence 2) 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. | 4 |
| Part A-Cohort 1 (Sequence 3) 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. | 3 |
| Part A-Cohort 2 (Sequence 1) 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. | 3 |
| Part A-Cohort 2 (Sequence 2) 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. | 3 |
| Part A-Cohort 2 (Sequence 3) 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. | 3 |
| Part B, 6 mg LY3323795 Participants received 6 mg of LY3323795 orally. | 6 |
| Part B, 20 mg LY3323795 Participants received 20 mg of LY3323795 orally. | 5 |
| Part B, 80 mg LY3323795 Participants received 80 mg of LY3323795 orally. | 6 |
| Part B, Placebo Participants received placebo identical to LY3323795 orally. | 6 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | 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 A-Cohort 1 (Sequence 1) | Part B, 6 mg LY3323795 | Part B, 20 mg LY3323795 | Part B, 80 mg LY3323795 | Part B, Placebo |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 6 Participants | 4 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 5 Participants | 5 Participants | 6 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 42 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 11 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 31 Participants | 4 Participants | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 5 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 9 | 2 / 6 | 0 / 6 | 0 / 6 | 1 / 9 | 1 / 6 | 0 / 6 | 2 / 6 | 5 / 6 | 3 / 5 | 6 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
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)
Population: All randomized participants who received study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A, Cohort 1, Placebo | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Part A, Cohort 1, 0.3 mg LY3323795 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Part A, Cohort 1, 3 mg LY3323795 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Part A, Cohort 1, 30 mg LY3323795 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Part A, Cohort 2, Placebo | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Part A, Cohort 2, 1 mg LY3323795 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Part A, Cohort 2, 10 mg LY3323795 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Part A, Cohort 2, 100 mg LY3323795 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Part B, Placebo | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Part B, 6 mg LY3323795 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Part B, 20 mg LY3323795 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Part B, 80 mg LY3323795 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
Secondary
Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1, Placebo | Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ 1-40 | -51 Picogram per milliliter (pg/mL) | Standard Deviation 21 |
| Part A, Cohort 1, Placebo | Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ 1-42 | -37 Picogram per milliliter (pg/mL) | Standard Deviation 23 |
| Part A, Cohort 1, 0.3 mg LY3323795 | Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ 1-42 | -71 Picogram per milliliter (pg/mL) | Standard Deviation 10 |
| Part A, Cohort 1, 0.3 mg LY3323795 | Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ 1-40 | -69 Picogram per milliliter (pg/mL) | Standard Deviation 6 |
| Part A, Cohort 1, 3 mg LY3323795 | Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ 1-40 | -88 Picogram per milliliter (pg/mL) | Standard Deviation 4 |
| Part A, Cohort 1, 3 mg LY3323795 | Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ 1-42 | -81 Picogram per milliliter (pg/mL) | Standard Deviation 7 |
| Part A, Cohort 1, 30 mg LY3323795 | Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ 1-40 | -12 Picogram per milliliter (pg/mL) | Standard Deviation 11 |
| Part A, Cohort 1, 30 mg LY3323795 | Part B Pharmacodynamics (PD): Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ 1-42 | -17 Picogram per milliliter (pg/mL) | Standard Deviation 23 |
Comparison: Aβ 1-40p-value: 0.21590% CI: [-29.52, 10.96]Mixed Models Analysis
Comparison: Aβ 1-40p-value: <0.00190% CI: [-69.79, -48.43]Mixed Models Analysis
Comparison: Aβ 1-40p-value: <0.00190% CI: [-90.21, -82.92]Mixed Models Analysis
Comparison: Aβ 1-42p-value: 0.01590% CI: [-33.69, -2.51]Mixed Models Analysis
Comparison: Aβ 1-42p-value: <0.00190% CI: [-72.23, -56.92]Mixed Models Analysis
Comparison: Aβ 1-42p-value: <0.00190% CI: [-88.97, -78.38]Mixed Models Analysis
Secondary
Part B Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Cerebrospinal Fluid (CSF)
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
Population: All randomized participants from Part B group, who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A, Cohort 1, Placebo | Part B Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Cerebrospinal Fluid (CSF) | 5.46 ng*h/mL | Geometric Coefficient of Variation 24 |
| Part A, Cohort 1, 0.3 mg LY3323795 | Part B Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Cerebrospinal Fluid (CSF) | 13.7 ng*h/mL | Geometric Coefficient of Variation 16 |
| Part A, Cohort 1, 3 mg LY3323795 | Part B Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Cerebrospinal Fluid (CSF) | 55.1 ng*h/mL | Geometric Coefficient of Variation 48 |
Secondary
Part B Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Cerebrospinal Fluid (CSF)
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
Population: All randomized participants from Part B group, who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A, Cohort 1, Placebo | Part B Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Cerebrospinal Fluid (CSF) | 0.293 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| Part A, Cohort 1, 0.3 mg LY3323795 | Part B Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Cerebrospinal Fluid (CSF) | 0.788 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 11 |
| Part A, Cohort 1, 3 mg LY3323795 | Part B Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Cerebrospinal Fluid (CSF) | 2.86 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
Secondary
Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A, Cohort 1, Placebo | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-42 | -22 Picogram per milliliter (pg/mL) | Standard Deviation 7 |
| Part A, Cohort 1, Placebo | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-40 | -39 Picogram per milliliter (pg/mL) | Standard Deviation 8 |
| Part A, Cohort 1, 0.3 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-42 | -33 Picogram per milliliter (pg/mL) | Standard Deviation 6 |
| Part A, Cohort 1, 0.3 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-40 | -52 Picogram per milliliter (pg/mL) | Standard Deviation 6 |
| Part A, Cohort 1, 3 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-42 | -49 Picogram per milliliter (pg/mL) | Standard Deviation 5 |
| Part A, Cohort 1, 3 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-40 | -71 Picogram per milliliter (pg/mL) | Standard Deviation 7 |
| Part A, Cohort 1, 30 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-40 | -76 Picogram per milliliter (pg/mL) | Standard Deviation 4 |
| Part A, Cohort 1, 30 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-42 | -60 Picogram per milliliter (pg/mL) | Standard Deviation 5 |
| Part A, Cohort 2, Placebo | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-40 | -76 Picogram per milliliter (pg/mL) | Standard Deviation 18 |
| Part A, Cohort 2, Placebo | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-42 | -63 Picogram per milliliter (pg/mL) | Standard Deviation 8 |
| Part A, Cohort 2, 1 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-42 | -75 Picogram per milliliter (pg/mL) | Standard Deviation 3 |
| Part A, Cohort 2, 1 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-40 | -89 Picogram per milliliter (pg/mL) | Standard Deviation 2 |
| Part A, Cohort 2, 10 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-42 | -54 Picogram per milliliter (pg/mL) | Standard Deviation 11 |
| Part A, Cohort 2, 10 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-40 | -79 Picogram per milliliter (pg/mL) | Standard Deviation 7 |
| Part A, Cohort 2, 100 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-40 | -81 Picogram per milliliter (pg/mL) | Standard Deviation 5 |
| Part A, Cohort 2, 100 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-42 | -58 Picogram per milliliter (pg/mL) | Standard Deviation 6 |
| Part B, Placebo | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-40 | -89 Picogram per milliliter (pg/mL) | Standard Deviation 1 |
| Part B, Placebo | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-42 | -64 Picogram per milliliter (pg/mL) | Standard Deviation 9 |
| Part B, 6 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-42 | -12 Picogram per milliliter (pg/mL) | Standard Deviation 6 |
| Part B, 6 mg LY3323795 | Pharmacodynamics (PD): Change From Baseline in Plasma Amyloid Beta (Aβ)₁-₄₀ and Aβ₁-₄₂ | Aβ1-40 | -23 Picogram per milliliter (pg/mL) | Standard Deviation 11 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma
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
Population: All randomized participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A, Cohort 1, Placebo | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma | 5.67 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 69 |
| Part A, Cohort 1, 0.3 mg LY3323795 | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma | 25.2 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 28 |
| Part A, Cohort 1, 3 mg LY3323795 | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma | 73.4 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 31 |
| Part A, Cohort 1, 30 mg LY3323795 | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma | 274 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 14 |
| Part A, Cohort 2, Placebo | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma | 663 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 35 |
| Part A, Cohort 2, 1 mg LY3323795 | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma | 2370 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 29 |
| Part A, Cohort 2, 10 mg LY3323795 | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma | 156 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 17 |
| Part A, Cohort 2, 100 mg LY3323795 | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma | 441 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 24 |
| Part B, Placebo | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3323795 in Plasma | 1950 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 49 |
Secondary
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma
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
Population: All randomized participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A, Cohort 1, Placebo | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma | 0.503 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| Part A, Cohort 1, 0.3 mg LY3323795 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma | 1.77 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 29 |
| Part A, Cohort 1, 3 mg LY3323795 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma | 4.79 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| Part A, Cohort 1, 30 mg LY3323795 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma | 15.7 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Part A, Cohort 2, Placebo | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma | 34.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| Part A, Cohort 2, 1 mg LY3323795 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma | 89.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 44 |
| Part A, Cohort 2, 10 mg LY3323795 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma | 10.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 45 |
| Part A, Cohort 2, 100 mg LY3323795 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma | 27.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| Part B, Placebo | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3323795 in Plasma | 88.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |