Healthy Volunteers, Alzheimer Disease
Conditions
Brief summary
This study involves single and multiple doses of LY3202626 and will evaluate the effects of LY3202626 on the body. There will be 4 parts to this study. In Parts A and B, single increasing doses of LY3202626 will be given in capsule form. Part A will also include itraconazole given orally as a solution. Part A will last approximately 8-12 weeks. Part B will last approximately 5-6 weeks. In Parts C and D, participants will be dosed multiple days with the study drug. Part C will last approximately 11-14 weeks. Part D will last approximately 11-14 weeks and participants must have Alzheimer's Disease. Participants may only enroll in one part.
Interventions
DRUGLY3202626
administered orally
DRUGPlacebo (Part A, B, C)
administered orally
DRUGItraconazole
administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* For Parts A, B, and C, are overtly healthy males or females (nonchildbearing potential), as determined by medical history and physical examination * Have a body mass index (BMI) of 18 to 32 kilograms per square meter (kg/m\^2) * For Part D, present with Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD) or mild to moderate AD * Have venous access sufficient to allow for blood sampling * Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures and research unit policies
Exclusion criteria
* Taking over-the-counter or prescription medication with the exception of vitamins or minerals * Smoke more than 10 cigarettes per day * Are unwilling or unable to refrain from eating any food or drinking any beverage containing grapefruit or grapefruit juice for at least 2 weeks prior to first dose until completion of the study
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 14 weeks) | A summary of other nonserious Adverse Events (AE's), and all SAE's, regardless of causality, is located in the Reported Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | Part A and B Day 1: Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose; Part C Day 1:Presdose, 0.5,1, 2, 4, 6, 8,12 hours postdose; Day 14: Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 216 hours postdose | Pharmacokinetic parameters for Part A and B were assessed on Day 1 using AUC 0-infinity (AUC0-inf). Pharmacokinetic parameters for Part C were assessed on Day 1 using AUC zero to time to last (AUC0-tlast), Day 14 using AUC steady state. |
| Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | Part A Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 postdose; Part C Day 14: Predose 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 120, 168, and 216 postdose | Plasma minimum A-beta 1-40 concentration or nadir concentration (Cnadir) is defined as the lowest concentration of plasma A-beta 1-40 following dose administration. |
| Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | Part A and B Day 1:Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose; Part C Day 1:Predose, 0.5,1, 2, 4, 6, 8, and 12 hours postdose; Part C Day 14:Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 216 hours postdose | Summary of PK parameters of LY3202626 in plasma following oral administration of single doses for Parts A and B and multiple doses for Part C. |
| PK: CSF Concentration of LY3202626 | Part C: Day 15 at 24 hours +/- 4 hours (hr) postdose | — |
| PD Biomarker: Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid-beta Peptide (A-beta) 1-40 Concentration | Parts C: Baseline, Day 15 | CSF Aβ1-40 change from baseline at Day 15 endpoint, 24 hours postdose (+/- 4 hours) following multiple doses of LY3202626. |
| PD Biomarker: Cerebral Spinal Fluid (CSF) Minimum Amyloid-beta Peptide (A-beta) 1-40 Concentration | Part B: -4, -2, Predose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24, 28, 32, and 36 hours postdose | CSF minimum A-beta 1-40 concentration or nadir concentration (Cnadir) is defined as the lowest concentration of CSF A-beta 1-40 following dose administration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A Cohort 1 Escalating single dose given orally (PO)per randomly assigned treatment sequence of 0.1mg, 1.6mg, 15mg LY3202626 or placebo. | 12 |
| Part A Cohort 2 Escalating single dose given PO per randomly assigned treatment sequence of 0.4mg, 5mg, or 45mg LY3202626, placebo.
Some participants may also receive multiple doses of 200 mg of Itraconazole PO in 1 period with 0.4mg of LY3202626. | 12 |
| Part A Food Effect Cohort 3 Single dose of 10mg LY3202626 given PO in Period 1 and Period 2 only. | 12 |
| Part B Cohort 4 Single oral dose of 1.6mg LY3202626 or placebo given PO in Period 1. Dose determined by Part A. | 6 |
| Part B Cohort 5 Single oral dose of 10mg LY3202626 or placebo given PO in in Period 1. Dose determined by Part A. | 8 |
| Part B Cohort 6 Single oral dose of 26mg LY3202626 or placebo given PO in Period 1. Dose determined by Part A. | 6 |
| Part C Cohort 7 Multiple oral doses of 1mg LY3202626 given PO once daily for 14 days. Dose determined by Part B. | 12 |
| Part C Cohort 8 Multiple oral doses of 6mg LY3202626 given PO once daily for 14 days. Dose determined by Part B. | 12 |
| Part C Cohort 9 Multiple oral doses of 26mg LY3202626 given PO once daily for 14 days. Dose determined by Part B. | 12 |
| Part D Cohort 10 Multiple oral doses of 6mg LY3202626 given PO once daily for 14 days. Dose determined by Part B. | 2 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 3 | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 3 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A Cohort 1 | Total | Part D Cohort 10 | Part C Cohort 9 | Part C Cohort 8 | Part C Cohort 7 | Part B Cohort 6 | Part B Cohort 5 | Part B Cohort 4 | Part A Food Effect Cohort 3 | Part A Cohort 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.0 years STANDARD_DEVIATION 8.1 | 38.70 years STANDARD_DEVIATION 10.93 | 68.0 years STANDARD_DEVIATION 2.8 | 40.5 years STANDARD_DEVIATION 10.5 | 40.4 years STANDARD_DEVIATION 8.1 | 37.5 years STANDARD_DEVIATION 10.5 | 35.2 years STANDARD_DEVIATION 7.2 | 43.0 years STANDARD_DEVIATION 11.3 | 36.5 years STANDARD_DEVIATION 12.4 | 39.0 years STANDARD_DEVIATION 13.6 | 36.9 years STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 18 Participants | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 76 Participants | 2 Participants | 9 Participants | 9 Participants | 10 Participants | 3 Participants | 7 Participants | 6 Participants | 9 Participants | 11 Participants |
| Ethnicity (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) 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 | 6 Participants | 30 Participants | 2 Participants | 4 Participants | 4 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 18 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 3 Participants | 44 Participants | 0 Participants | 7 Participants | 5 Participants | 4 Participants | 5 Participants | 7 Participants | 4 Participants | 5 Participants | 4 Participants |
| Region of Enrollment United States | 12 participants | 94 participants | 2 participants | 12 participants | 12 participants | 12 participants | 6 participants | 8 participants | 6 participants | 12 participants | 12 participants |
| Sex: Female, Male Female | 1 Participants | 10 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 11 Participants | 84 Participants | 0 Participants | 11 Participants | 11 Participants | 12 Participants | 6 Participants | 8 Participants | 6 Participants | 8 Participants | 11 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 | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 36 | 0 / 8 | 1 / 8 | 7 / 12 | 4 / 9 | 4 / 13 | 3 / 8 | 6 / 11 | 7 / 19 | 2 / 11 | 13 / 14 | 1 / 8 |
| serious Total, serious adverse events | 0 / 36 | 0 / 8 | 0 / 8 | 0 / 12 | 0 / 9 | 0 / 13 | 0 / 8 | 0 / 11 | 0 / 19 | 0 / 11 | 0 / 14 | 0 / 8 |
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
A summary of other nonserious Adverse Events (AE's), and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline to Study Completion (up to 14 weeks)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A, B, and C Placebo (PBO) | 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 0.1mg LY3202626 | 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 0.4mg LY3202626 | 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 0.4mg LY3202626 + 200mg Itraconazole | 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 C 1mg LY3202626 QD | 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 and B 1.6mg LY3202626 | 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 5mg LY3202626 | 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 C and D 6mg LY3202626 QD | 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, B and C 10mg LY3202626 | 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 15mg LY3202626 | 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 and C 26mg LY3202626 | 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 45mg LY3202626 | 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
PD Biomarker: Cerebral Spinal Fluid (CSF) Minimum Amyloid-beta Peptide (A-beta) 1-40 Concentration
CSF minimum A-beta 1-40 concentration or nadir concentration (Cnadir) is defined as the lowest concentration of CSF A-beta 1-40 following dose administration.
Time frame: Part B: -4, -2, Predose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24, 28, 32, and 36 hours postdose
Population: All participants in Part B who received at least one dose of study drug and had evaluable CSF PD data analyzed per protocol. Participants in Part A, C and D were not assessed per protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A, B, and C Placebo (PBO) | PD Biomarker: Cerebral Spinal Fluid (CSF) Minimum Amyloid-beta Peptide (A-beta) 1-40 Concentration | 7980 pg/mL | Geometric Coefficient of Variation 53.8 |
| Part A 0.1mg LY3202626 | PD Biomarker: Cerebral Spinal Fluid (CSF) Minimum Amyloid-beta Peptide (A-beta) 1-40 Concentration | 5700 pg/mL | Geometric Coefficient of Variation 22.3 |
| Part A 0.4mg LY3202626 | PD Biomarker: Cerebral Spinal Fluid (CSF) Minimum Amyloid-beta Peptide (A-beta) 1-40 Concentration | 5770 pg/mL | Geometric Coefficient of Variation 41.8 |
| Part A 0.4mg LY3202626 + 200mg Itraconazole | PD Biomarker: Cerebral Spinal Fluid (CSF) Minimum Amyloid-beta Peptide (A-beta) 1-40 Concentration | 2980 pg/mL | Geometric Coefficient of Variation 46.4 |
Secondary
PD Biomarker: Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid-beta Peptide (A-beta) 1-40 Concentration
CSF Aβ1-40 change from baseline at Day 15 endpoint, 24 hours postdose (+/- 4 hours) following multiple doses of LY3202626.
Time frame: Parts C: Baseline, Day 15
Population: All participants in Part C who received at least one dose of study drug and had evaluable CSF PD data analyzed. Participants in Part A, B and D were not assessed per protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A, B, and C Placebo (PBO) | PD Biomarker: Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid-beta Peptide (A-beta) 1-40 Concentration | -21.3 percent change in concentration | Standard Deviation 16.8 |
| Part A 0.1mg LY3202626 | PD Biomarker: Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid-beta Peptide (A-beta) 1-40 Concentration | -50.1 percent change in concentration | Standard Deviation 8.56 |
| Part A 0.4mg LY3202626 | PD Biomarker: Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid-beta Peptide (A-beta) 1-40 Concentration | -75.7 percent change in concentration | Standard Deviation 7.38 |
| Part A 0.4mg LY3202626 + 200mg Itraconazole | PD Biomarker: Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid-beta Peptide (A-beta) 1-40 Concentration | -93.7 percent change in concentration | Standard Deviation 2.39 |
Secondary
Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration
Plasma minimum A-beta 1-40 concentration or nadir concentration (Cnadir) is defined as the lowest concentration of plasma A-beta 1-40 following dose administration.
Time frame: Part A Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 postdose; Part C Day 14: Predose 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 120, 168, and 216 postdose
Population: All participants in Part A, Periods 1-3 and Part C, Period 3, who received at least one dose of study drug and had evaluable PD data analyzed per protocol. Participants in Part B and D were not assessed per protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A, B, and C Placebo (PBO) | Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | 107 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 35.1 |
| Part A 0.1mg LY3202626 | Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | 58.1 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 150 |
| Part A 0.4mg LY3202626 | Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | 61.8 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 25.6 |
| Part A 0.4mg LY3202626 + 200mg Itraconazole | Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | 33.4 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 62 |
| Part C 1mg LY3202626 QD | Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | 25.2 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 16.8 |
| Part A and B 1.6mg LY3202626 | Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | 17.0 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 33.6 |
| Part A 5mg LY3202626 | Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | 7.93 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 42 |
| Part C and D 6mg LY3202626 QD | Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | 84.6 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 26.5 |
| Part A, B and C 10mg LY3202626 | Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | 24.0 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 33.1 |
| Part A 15mg LY3202626 | Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | 5.80 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 51.9 |
| Part B and C 26mg LY3202626 | Pharmacodynamic(PD) Biomarker: Plasma Minimum Amyloid-Beta Peptide (A-beta) 1-40 Concentration | 4.2 Picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 0 |
Secondary
Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626
Summary of PK parameters of LY3202626 in plasma following oral administration of single doses for Parts A and B and multiple doses for Part C.
Time frame: Part A and B Day 1:Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose; Part C Day 1:Predose, 0.5,1, 2, 4, 6, 8, and 12 hours postdose; Part C Day 14:Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 216 hours postdose
Population: All participants in Part A, B, and C who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A, B, and C Placebo (PBO) | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 0.169 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50 |
| Part A 0.1mg LY3202626 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 0.486 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 81 |
| Part A 0.4mg LY3202626 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 2.89 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 70 |
| Part A 0.4mg LY3202626 + 200mg Itraconazole | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 7.91 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| Part C 1mg LY3202626 QD | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 21.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 77 |
| Part A and B 1.6mg LY3202626 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 92.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| Part A 5mg LY3202626 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 2.90 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 86 |
| Part C and D 6mg LY3202626 QD | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 3.75 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 176 |
| Part A, B and C 10mg LY3202626 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 36.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 126 |
| Part A 15mg LY3202626 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 2.57 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 2.5 |
| Part B and C 26mg LY3202626 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 11.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 71 |
| Part A 45mg LY3202626 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3202626 | 72.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 61 |
Secondary
PK: Area Under the Concentration Time Curve (AUC) of LY3202626
Pharmacokinetic parameters for Part A and B were assessed on Day 1 using AUC 0-infinity (AUC0-inf). Pharmacokinetic parameters for Part C were assessed on Day 1 using AUC zero to time to last (AUC0-tlast), Day 14 using AUC steady state.
Time frame: Part A and B Day 1: Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose; Part C Day 1:Presdose, 0.5,1, 2, 4, 6, 8,12 hours postdose; Day 14: Predose, 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 216 hours postdose
Population: All participants in Parts A, B, and C who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A, B, and C Placebo (PBO) | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | NA nanogram x hour/milliliter (ng*hr/mL) | — |
| Part A 0.1mg LY3202626 | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | NA nanogram x hour/milliliter (ng*hr/mL) | — |
| Part A 0.4mg LY3202626 | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | 60.6 nanogram x hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 49 |
| Part A 0.4mg LY3202626 + 200mg Itraconazole | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | 197 nanogram x hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
| Part C 1mg LY3202626 QD | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | 393 nanogram x hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 84 |
| Part A and B 1.6mg LY3202626 | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | 1680 nanogram x hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
| Part A 5mg LY3202626 | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | 49.9 nanogram x hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 41 |
| Part C and D 6mg LY3202626 QD | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | 102 nanogram x hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 111 |
| Part A, B and C 10mg LY3202626 | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | 575 nanogram x hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 62 |
| Part A 15mg LY3202626 | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | 38.6 nanogram x hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 25 |
| Part B and C 26mg LY3202626 | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | 151 nanogram x hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 54 |
| Part A 45mg LY3202626 | PK: Area Under the Concentration Time Curve (AUC) of LY3202626 | 1020 nanogram x hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 50 |
Secondary
PK: CSF Concentration of LY3202626
Time frame: Part C: Day 15 at 24 hours +/- 4 hours (hr) postdose
Population: All participants in Part C who received at least one dose of study drug and had evaluable CSF PK data per protocol. Participants in Part A, B and D were not assessed per protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A, B, and C Placebo (PBO) | PK: CSF Concentration of LY3202626 | 0.0648 ng/mL | Geometric Coefficient of Variation 46.2 |
| Part A 0.1mg LY3202626 | PK: CSF Concentration of LY3202626 | 0.202 ng/mL | Geometric Coefficient of Variation 48.9 |
| Part A 0.4mg LY3202626 | PK: CSF Concentration of LY3202626 | 1.26 ng/mL | Geometric Coefficient of Variation 44.8 |