Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to evaluate how safe LY2969822 (study drug) is and whether it causes any side effects. The study will also measure how much of the study drug gets into the blood stream and how long it takes the body to get rid of the study drug. This is the first time that this study drug is being given to participants. This study is for research purposes only and is not intended to treat any medical condition.
Detailed description
Participants in Part A will complete three study periods, which together will last about 40 days. Participants in Parts B and C will complete one study period which will last about 17 days, but the total study time is about 40 days. Each participant may only enroll in one part. Screening is required within 28 days prior to the start of the study for all participants.
Interventions
DRUGLY2969822
Capsules administered orally
DRUGPlacebo
Capsules administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male participants must agree to use a reliable method of birth control in addition to having their partner use another method for the duration of the study and for 3 months after the last dose of LY2969822 * Female participants must not be of child-bearing potential * Participants have a body mass index (BMI) of 18.5 to 29.9 kilogram per meter square (kg/m\^2), inclusive, at screening
Exclusion criteria
* Have participated, within the last 30 days (prior to first dose in this study), in a clinical trial involving an investigational product * Have a significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data * Intended use of over-the-counter medication within 14 days prior to dosing or during the study with the exception of vitamins and mineral supplements or occasional paracetamol or acetaminophen * Intended use of herbal supplements or prescription medications, other than stable doses of thyroid or estrogen hormone replacement, within 14 days prior to dosing or during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Baseline Through End of Study (up to Week 7) | A summary of other nonserious adverse events (AEs) and all SAEs, regardless of causality, is located in the Reported Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | All Cohorts: Day 1 - 0 Hours (H), 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohort 3: Day 10 - 0 H, 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohorts 3 - 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 |
| PK: Maximum Cerebrospinal Fluid Concentrations (CSF Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | Cohort 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H | PK: Maximum Cerebrospinal Fluid Concentrations (CSF Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 |
| PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | All Cohorts: Day 1 - 0 Hours (H), 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohort 3: Day 10 - 0 H, 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohorts 3 - 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H | For Cohorts 1-2, AUC is extrapolated from time zero to infinity (AUC\[0-inf\]). For Cohorts 3 - 8, AUC is reported during one dosing interval (AUC\[tau\]). AUC(tau) is 24 hours for Cohorts 3 - 5 and 12 hours for Cohorts 6 - 8. |
| PK: CSF AUC(Tau) of Prodrug LY2969822 and Active Metabolite LSN2934747 | Cohort 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H | AUC(tau) is 12 hours. |
Countries
Singapore
Participant flow
Pre-assignment details
This study had 3 parts. Part A-Single ascending dose, 3-period, crossover study (Cohorts 1-2). Part B-Multiple ascending dose, parallel study (Cohorts 3-7). Part C-Multiple dose, single dose level study (Cohort 8). Each participant enrolled in 1 cohort. Replacement participants received interventions intended for those that discontinued early.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Cohorts 1-2 Part A Single Ascending Dose (SAD): Cohort 1 received placebo, 2 mg, 20 mg, or 40 mg LY2969822 PO, once, in each of 3 study periods. Cohort 2 received placebo, 6 mg, 60 mg, or 20 mg LY2969822 PO, once, in each of 3 study periods. At least 5 days elapsed between doses of study drug. | 18 |
| Part B: Placebo Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.) | 15 |
| Part B: Cohorts 3 Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.) | 9 |
| Part B: Cohorts 4 Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.) | 9 |
| Part B: Cohorts 5 Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.) | 9 |
| Part B: Cohorts 6 Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.) | 9 |
| Part B: Cohorts 7 Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.) | 9 |
| Part C: Cohort 8 Part C Multiple Dose, Single Dose Level: Cohort 8A received either placebo or up to 40 LY2969822 BID, PO, for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.) Cohort 8B received either placebo or up to 20 mg LY2969822 BID, PO, for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, and 20 mg BID for 10 days.) | 21 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A: Cohorts 1-2: Period 3 | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B: Cohorts 3-7 Overall | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 4 | 0 | 0 | 0 |
| Part C: Cohort 8 Overall | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 0 |
| Part C: Cohort 8 Overall | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Part B: Placebo | Part B: Cohorts 3 | Part B: Cohorts 4 | Part A: Cohorts 1-2 | Part B: Cohorts 5 | Part B: Cohorts 6 | Part B: Cohorts 7 | Part C: Cohort 8 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Part A | NA years | NA years | NA years | 35.1 years STANDARD_DEVIATION 9.5 | NA years | NA years | NA years | NA years | 35.1 years STANDARD_DEVIATION 9.5 |
| Age, Continuous Part B | 32.6 years STANDARD_DEVIATION 7.6 | 32.7 years STANDARD_DEVIATION 7.4 | 34.6 years STANDARD_DEVIATION 6.8 | NA years | 32.2 years STANDARD_DEVIATION 6.7 | 31.6 years STANDARD_DEVIATION 5.7 | 35.1 years STANDARD_DEVIATION 10.6 | NA years | 33.1 years STANDARD_DEVIATION 7.4 |
| Age, Continuous Part C | NA years | NA years | NA years | NA years | NA years | NA years | NA years | 40.3 years STANDARD_DEVIATION 5.3 | 40.3 years STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 9 Participants | 9 Participants | 18 Participants | 9 Participants | 9 Participants | 9 Participants | 21 Participants | 99 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 |
| 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 |
| Race (NIH/OMB) Asian | 14 Participants | 9 Participants | 8 Participants | 18 Participants | 9 Participants | 8 Participants | 9 Participants | 21 Participants | 96 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 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 |
| 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 |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Region of Enrollment Singapore | 15 Participants | 9 Participants | 9 Participants | 18 Participants | 9 Participants | 9 Participants | 9 Participants | 21 Participants | 99 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 9 Participants | 9 Participants | 18 Participants | 9 Participants | 9 Participants | 9 Participants | 21 Participants | 99 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 | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 18 | 3 / 6 | 4 / 6 | 8 / 12 | 4 / 5 | 6 / 6 | 8 / 9 | 5 / 6 | 12 / 18 | 8 / 9 | 17 / 18 | 21 / 27 | 16 / 17 | 16 / 18 | 15 / 16 | 8 / 9 | 8 / 8 | 10 / 10 | 10 / 11 | 10 / 11 | 11 / 11 | 4 / 4 |
| serious Total, serious adverse events | 0 / 18 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 5 | 0 / 6 | 0 / 9 | 0 / 6 | 0 / 18 | 0 / 9 | 0 / 18 | 0 / 27 | 0 / 17 | 0 / 18 | 0 / 16 | 0 / 9 | 0 / 8 | 0 / 10 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 4 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration
A summary of other nonserious adverse events (AEs) and all SAEs, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline Through End of Study (up to Week 7)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 - Placebo | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 1 - 2 mg LY2969822 | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 1 - 20 mg LY2969822 | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 1 - 40 mg LY2969822 | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 2 - Placebo | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 2 - 6 mg LY2969822 | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 2 - 60 mg LY2969822 | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 2 - 20 mg LY2969822 | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohorts 3-7 - Placebo | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 3 - 20 mg LY2969822 QD | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 4 - 40 mg LY2969822 QD Titrated | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 5 - 80 mg LY2969822 QD Titrated | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 6 - 80 mg LY2969822 BID Titrated | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 8 - Placebo BID | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 8A - 40 mg LY2969822 BID Titrated | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
| Cohort 8B - 20 mg LY2969822 BID Titrated | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 participants |
Secondary
Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747
Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747
Time frame: All Cohorts: Day 1 - 0 Hours (H), 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohort 3: Day 10 - 0 H, 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohorts 3 - 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H
Population: All participants who received at least one dose of LY2969822 and had evaluable plasma values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - Placebo | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 108 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 21 |
| Cohort 1 - Placebo | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 19.9 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 28 |
| Cohort 1 - 2 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 978 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 10 |
| Cohort 1 - 2 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 209 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 20 |
| Cohort 1 - 20 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 346 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 21 |
| Cohort 1 - 20 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 1700 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 19 |
| Cohort 1 - 40 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 289 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 43 |
| Cohort 1 - 40 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 63.3 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 33 |
| Cohort 2 - Placebo | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 2850 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 18 |
| Cohort 2 - Placebo | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 646 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 31 |
| Cohort 2 - 6 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 197 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 22 |
| Cohort 2 - 6 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 840 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 20 |
| Cohort 2 - 60 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 847 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 30 |
| Cohort 2 - 60 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 192 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 47 |
| Cohort 2 - 20 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 1200 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 18 |
| Cohort 2 - 20 mg LY2969822 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 216 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 33 |
| Cohorts 3-7 - Placebo | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 341 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 33 |
| Cohorts 3-7 - Placebo | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 1520 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 14 |
| Cohort 3 - 20 mg LY2969822 QD | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 232 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 35 |
| Cohort 3 - 20 mg LY2969822 QD | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 51.3 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 67 |
| Cohort 4 - 40 mg LY2969822 QD Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 340 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 35 |
| Cohort 4 - 40 mg LY2969822 QD Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 1600 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 20 |
| Cohort 5 - 80 mg LY2969822 QD Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 60.2 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 28 |
| Cohort 5 - 80 mg LY2969822 QD Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 332 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 31 |
| Cohort 6 - 80 mg LY2969822 BID Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 4190 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 28 |
| Cohort 6 - 80 mg LY2969822 BID Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 771 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 51 |
| Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 49.8 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 34 |
| Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 303 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 35 |
| Cohort 8 - Placebo BID | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 788 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 30 |
| Cohort 8 - Placebo BID | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 4130 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 14 |
| Cohort 8A - 40 mg LY2969822 BID Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 85.9 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 43 |
| Cohort 8A - 40 mg LY2969822 BID Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 461 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 50 |
| Cohort 8B - 20 mg LY2969822 BID Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 2390 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 17 |
| Cohort 8B - 20 mg LY2969822 BID Titrated | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 539 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 35 |
| Cohort 8A - 6 mg LY2969822 BID Day 1 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 61.3 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 59 |
| Cohort 8A - 6 mg LY2969822 BID Day 1 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 381 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 21 |
| Cohort 8A - 40 mg BID LY2969822 Day 14 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | NA nanomoles per liter (nmol/L) | — |
| Cohort 8A - 40 mg BID LY2969822 Day 14 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | NA nanomoles per liter (nmol/L) | — |
| Cohort 8B - 6 mg LY2969822 BID Day 1 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 44.9 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 35 |
| Cohort 8B - 6 mg LY2969822 BID Day 1 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 263 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 29 |
| Cohort 8B - 20 mg BID LY2969822 Day 14 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 216 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 32 |
| Cohort 8B - 20 mg BID LY2969822 Day 14 | Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 1150 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 14 |
Secondary
PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747
For Cohorts 1-2, AUC is extrapolated from time zero to infinity (AUC\[0-inf\]). For Cohorts 3 - 8, AUC is reported during one dosing interval (AUC\[tau\]). AUC(tau) is 24 hours for Cohorts 3 - 5 and 12 hours for Cohorts 6 - 8.
Time frame: All Cohorts: Day 1 - 0 Hours (H), 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohort 3: Day 10 - 0 H, 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohorts 3 - 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H
Population: All participants who received at least one dose of LY2969822 and had evaluable plasma values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - Placebo | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 88.5 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 22 |
| Cohort 1 - Placebo | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 805 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 18 |
| Cohort 1 - 2 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 7030 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 12 |
| Cohort 1 - 2 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 843 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 19 |
| Cohort 1 - 20 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 13500 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 25 |
| Cohort 1 - 20 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 1730 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 12 |
| Cohort 1 - 40 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 273 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 36 |
| Cohort 1 - 40 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 2090 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 39 |
| Cohort 2 - Placebo | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 23600 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 17 |
| Cohort 2 - Placebo | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 3700 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 26 |
| Cohort 2 - 6 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 1110 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 38 |
| Cohort 2 - 6 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 6970 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 22 |
| Cohort 2 - 60 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 5830 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 36 |
| Cohort 2 - 60 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 759 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 50 |
| Cohort 2 - 20 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 8220 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 15 |
| Cohort 2 - 20 mg LY2969822 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 896 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 27 |
| Cohorts 3-7 - Placebo | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 8660 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 12 |
| Cohorts 3-7 - Placebo | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 1160 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 25 |
| Cohort 3 - 20 mg LY2969822 QD | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 1710 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 28 |
| Cohort 3 - 20 mg LY2969822 QD | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 231 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 51 |
| Cohort 4 - 40 mg LY2969822 QD Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 10600 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 28 |
| Cohort 4 - 40 mg LY2969822 QD Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 1400 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 42 |
| Cohort 5 - 80 mg LY2969822 QD Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 244 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 36 |
| Cohort 5 - 80 mg LY2969822 QD Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 2100 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 26 |
| Cohort 6 - 80 mg LY2969822 BID Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 3430 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 55 |
| Cohort 6 - 80 mg LY2969822 BID Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 29000 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 30 |
| Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 1810 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 30 |
| Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 203 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 42 |
| Cohort 8 - Placebo BID | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 25300 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 18 |
| Cohort 8 - Placebo BID | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 2810 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 35 |
| Cohort 8A - 40 mg LY2969822 BID Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 363 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 46 |
| Cohort 8A - 40 mg LY2969822 BID Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 3010 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 49 |
| Cohort 8B - 20 mg LY2969822 BID Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 1820 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 40 |
| Cohort 8B - 20 mg LY2969822 BID Titrated | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 14400 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 19 |
| Cohort 8A - 6 mg LY2969822 BID Day 1 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 2670 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 20 |
| Cohort 8A - 6 mg LY2969822 BID Day 1 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 306 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 65 |
| Cohort 8A - 40 mg BID LY2969822 Day 14 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | NA nanomoles x hours per liter (nmol∙h/L) | — |
| Cohort 8A - 40 mg BID LY2969822 Day 14 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | NA nanomoles x hours per liter (nmol∙h/L) | — |
| Cohort 8B - 6 mg LY2969822 BID Day 1 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 207 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 44 |
| Cohort 8B - 6 mg LY2969822 BID Day 1 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 1790 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 20 |
| Cohort 8B - 20 mg BID LY2969822 Day 14 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 6920 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 18 |
| Cohort 8B - 20 mg BID LY2969822 Day 14 | PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 778 nanomoles x hours per liter (nmol∙h/L) | Geometric Coefficient of Variation 34 |
Secondary
PK: CSF AUC(Tau) of Prodrug LY2969822 and Active Metabolite LSN2934747
AUC(tau) is 12 hours.
Time frame: Cohort 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H
Population: CSF samples were only collected in Cohort 8. All participants in Cohort 8 who received at least one dose of LY2969822 and had evaluable CSF values on Day 14.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - Placebo | PK: CSF AUC(Tau) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | NA nmol∙h/L | — |
| Cohort 1 - Placebo | PK: CSF AUC(Tau) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | NA nmol∙h/L | — |
| Cohort 1 - 2 mg LY2969822 | PK: CSF AUC(Tau) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 831 nmol∙h/L | Geometric Coefficient of Variation 61 |
| Cohort 1 - 2 mg LY2969822 | PK: CSF AUC(Tau) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 75.1 nmol∙h/L | Geometric Coefficient of Variation 85 |
Secondary
PK: Maximum Cerebrospinal Fluid Concentrations (CSF Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747
PK: Maximum Cerebrospinal Fluid Concentrations (CSF Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747
Time frame: Cohort 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H
Population: CSF samples were only collected in Cohort 8. All participants in Cohort 8 who received at least one dose of LY2969822 and had evaluable CSF values on Day 14.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - Placebo | PK: Maximum Cerebrospinal Fluid Concentrations (CSF Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | NA nmol/L | — |
| Cohort 1 - Placebo | PK: Maximum Cerebrospinal Fluid Concentrations (CSF Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | NA nmol/L | — |
| Cohort 1 - 2 mg LY2969822 | PK: Maximum Cerebrospinal Fluid Concentrations (CSF Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LY2969822 | 8.42 nmol/L | Geometric Coefficient of Variation 106 |
| Cohort 1 - 2 mg LY2969822 | PK: Maximum Cerebrospinal Fluid Concentrations (CSF Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747 | LSN2934747 | 93.0 nmol/L | Geometric Coefficient of Variation 59 |