Healthy
Conditions
Brief summary
The study involves a single dose of LY3143753 or LY3185643, given as an injection into the abdomen. The study will evaluate the effects of the LY3143753 or LY3185643 on your body. The study is approximately 12 weeks for each participant, not including screening. Screening is required within 28 days prior to the start of the study. This study involves Part A (LY3143753) and Part B (LY3185643). Participants may only enroll in one part and at one dose level.
Interventions
DRUGLY3143753 (Part A)
Administered via SC injection
DRUGLY3185643 (Part B)
Administered via SC injection
DRUGPlacebo (Part A and Part B)
Administered via SC injection
DRUGrGlucagon (Part B)
Administered via SC injection
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
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy males or females * Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
Exclusion criteria
* Are investigator site personnel directly affiliated with this study and their immediate families * Are currently enrolled in a clinical trial involving an investigational product (IP) or off-label use of a drug or device * Have participated, within the last 3 months, in a clinical trial * Have known or ongoing psychiatric disorders * Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies * Show evidence of hepatitis C and/or positive hepatitis C antibody * Show evidence of hepatitis B and/or positive hepatitis B surface antigen * History of/current phaeochromocytoma * History of/current insulinoma
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 84 Days) | A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section. |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of Part A | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours |
| PK: Cmax of Part B | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours |
| PK: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Part A | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours |
| PK: AUC(0-∞) of Part B | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours |
| PK: Tmax of Part B | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours |
| Pharmacodynamic (PD): Absolute Maximum Blood Glucose of Part A | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours |
| PK: Time to Maximum Drug Concentration (Tmax) of Part A | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours |
| PD: Maximum Glucose Increase (Gmax) of Part A | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours |
| PD: Gmax of Part B | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours |
| PD: Time to Maximum Blood Glucose (Gtmax) of Part A | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours |
| PD: Gtmax of Part B | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours |
| QT Interval as Corrected by the Fridericia Method (QTcF) Change From Baseline of Part A | Baseline, 8 hours after drug administration |
| QTcF Change From Baseline of Part B | Baseline, 8 hours after drug administration |
| PD Absolute Maximum Blood Glucose of Part B | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY3143753 (Part A) Single subcutaneous (SC) injection of ascending doses of LY3143753 on Day 1. | 24 |
| LY3185643 (Part B) Single SC injection of ascending doses of LY3185643 on Day 1. | 44 |
| Total | 68 |
Baseline characteristics
| Characteristic | LY3143753 (Part A) | LY3185643 (Part B) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical >=65 years | 7 Participants | 2 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 40 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 44 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 41 Participants | 64 Participants |
| Region of Enrollment United Kingdom | 24 Participants | 44 Participants | 68 Participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 17 Participants | 37 Participants | 54 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 6 | 2 / 3 | 3 / 3 | 3 / 3 | 4 / 6 | 3 / 3 | 5 / 11 | 3 / 3 | 1 / 3 | 1 / 3 | 2 / 3 | 3 / 3 | 3 / 3 | 2 / 3 | 3 / 3 | 3 / 3 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 1 / 6 | 1 / 3 | 1 / 11 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 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
A summary of other 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 84 Days)
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Part A) | 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 |
| 0.05 mg of LY3143753 (Part A) | 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 |
| 0.1 mg of LY3143753 (Part A) | 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 |
| 0.2 mg of LY3143753 (Part A) | 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 |
| 0.4 mg of LY3143753 (Part A) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 1 Participants |
| 1 mg of LY3143753 (Part A) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 1 Participants |
| Placebo (Part B) | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 1 Participants |
| 0.01 mg of LY3185643 (Part B) | 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 |
| 0.03 mg of LY3185643 (Part B) | 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 |
| 0.05 mg of LY3185643 (Part B) | 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 |
| 0.06 mg of LY3185643 (Part B) | 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 |
| 0.1 mg of LY3185643 (Part B) | 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 |
| 0.2 mg of LY3185643 (Part B) | 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 |
| 0.3 mg of LY3185643 (Part B) | 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 0.48 mg of LY3185643 | 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 |
| 0.72 mg of LY3185643 (Part B) | 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 |
| r Glucagon (Part B) | 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 Absolute Maximum Blood Glucose of Part B
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
Population: All participants who received at least one dose of study drug or placebo and have evaluable PD data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | PD Absolute Maximum Blood Glucose of Part B | 95.1 mg/dL | Geometric Coefficient of Variation 5 |
| 0.05 mg of LY3143753 (Part A) | PD Absolute Maximum Blood Glucose of Part B | 103 mg/dL | Geometric Coefficient of Variation 11 |
| 0.1 mg of LY3143753 (Part A) | PD Absolute Maximum Blood Glucose of Part B | 98.1 mg/dL | Geometric Coefficient of Variation 10 |
| 0.2 mg of LY3143753 (Part A) | PD Absolute Maximum Blood Glucose of Part B | 128 mg/dL | Geometric Coefficient of Variation 36 |
| 0.4 mg of LY3143753 (Part A) | PD Absolute Maximum Blood Glucose of Part B | 117 mg/dL | Geometric Coefficient of Variation 7 |
| 1 mg of LY3143753 (Part A) | PD Absolute Maximum Blood Glucose of Part B | 167 mg/dL | Geometric Coefficient of Variation 16 |
| Placebo (Part B) | PD Absolute Maximum Blood Glucose of Part B | 186 mg/dL | Geometric Coefficient of Variation 7 |
| 0.01 mg of LY3185643 (Part B) | PD Absolute Maximum Blood Glucose of Part B | 146 mg/dL | Geometric Coefficient of Variation 16 |
| 0.03 mg of LY3185643 (Part B) | PD Absolute Maximum Blood Glucose of Part B | 192 mg/dL | Geometric Coefficient of Variation 16 |
| 0.05 mg of LY3185643 (Part B) | PD Absolute Maximum Blood Glucose of Part B | 188 mg/dL | Geometric Coefficient of Variation 3 |
| 0.06 mg of LY3185643 (Part B) | PD Absolute Maximum Blood Glucose of Part B | 162 mg/dL | Geometric Coefficient of Variation 11 |
Secondary
PD: Gmax of Part B
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable PD data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | PD: Gmax of Part B | 4.69 mg/dL | Geometric Coefficient of Variation 54 |
| 0.05 mg of LY3143753 (Part A) | PD: Gmax of Part B | 7.2 mg/dL | Geometric Coefficient of Variation 12.6 |
| 0.1 mg of LY3143753 (Part A) | PD: Gmax of Part B | 5.04 mg/dL | Geometric Coefficient of Variation 189 |
| 0.2 mg of LY3143753 (Part A) | PD: Gmax of Part B | 28.1 mg/dL | Geometric Coefficient of Variation 144 |
| 0.4 mg of LY3143753 (Part A) | PD: Gmax of Part B | 21.8 mg/dL | Geometric Coefficient of Variation 66 |
| 1 mg of LY3143753 (Part A) | PD: Gmax of Part B | 76.1 mg/dL | Geometric Coefficient of Variation 35 |
| Placebo (Part B) | PD: Gmax of Part B | 89.4 mg/dL | Geometric Coefficient of Variation 14 |
| 0.01 mg of LY3185643 (Part B) | PD: Gmax of Part B | 58.4 mg/dL | Geometric Coefficient of Variation 35 |
| 0.03 mg of LY3185643 (Part B) | PD: Gmax of Part B | 102 mg/dL | Geometric Coefficient of Variation 25 |
| 0.05 mg of LY3185643 (Part B) | PD: Gmax of Part B | 105 mg/dL | Geometric Coefficient of Variation 6 |
| 0.06 mg of LY3185643 (Part B) | PD: Gmax of Part B | 71.8 mg/dL | Geometric Coefficient of Variation 23 |
Secondary
PD: Gtmax of Part B
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable PD data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Part A) | PD: Gtmax of Part B | 0.5 hour |
| 0.05 mg of LY3143753 (Part A) | PD: Gtmax of Part B | 0.5 hour |
| 0.1 mg of LY3143753 (Part A) | PD: Gtmax of Part B | 0.67 hour |
| 0.2 mg of LY3143753 (Part A) | PD: Gtmax of Part B | 1.0 hour |
| 0.4 mg of LY3143753 (Part A) | PD: Gtmax of Part B | 0.67 hour |
| 1 mg of LY3143753 (Part A) | PD: Gtmax of Part B | 0.75 hour |
| Placebo (Part B) | PD: Gtmax of Part B | 1.17 hour |
| 0.01 mg of LY3185643 (Part B) | PD: Gtmax of Part B | 0.58 hour |
| 0.03 mg of LY3185643 (Part B) | PD: Gtmax of Part B | 1.17 hour |
| 0.05 mg of LY3185643 (Part B) | PD: Gtmax of Part B | 0.75 hour |
| 0.06 mg of LY3185643 (Part B) | PD: Gtmax of Part B | 0.46 hour |
Secondary
PD: Maximum Glucose Increase (Gmax) of Part A
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable PD data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | PD: Maximum Glucose Increase (Gmax) of Part A | 4.14 mg/dL | Geometric Coefficient of Variation 112 |
| 0.05 mg of LY3143753 (Part A) | PD: Maximum Glucose Increase (Gmax) of Part A | 66.1 mg/dL | Geometric Coefficient of Variation 63 |
| 0.1 mg of LY3143753 (Part A) | PD: Maximum Glucose Increase (Gmax) of Part A | 103 mg/dL | Geometric Coefficient of Variation 17 |
| 0.2 mg of LY3143753 (Part A) | PD: Maximum Glucose Increase (Gmax) of Part A | 84.9 mg/dL | Geometric Coefficient of Variation 18 |
| 0.4 mg of LY3143753 (Part A) | PD: Maximum Glucose Increase (Gmax) of Part A | 91.5 mg/dL | Geometric Coefficient of Variation 20 |
| 1 mg of LY3143753 (Part A) | PD: Maximum Glucose Increase (Gmax) of Part A | 79.8 mg/dL | Geometric Coefficient of Variation 40 |
Secondary
PD: Time to Maximum Blood Glucose (Gtmax) of Part A
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable PD data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Part A) | PD: Time to Maximum Blood Glucose (Gtmax) of Part A | 0.96 hour |
| 0.05 mg of LY3143753 (Part A) | PD: Time to Maximum Blood Glucose (Gtmax) of Part A | 1.00 hour |
| 0.1 mg of LY3143753 (Part A) | PD: Time to Maximum Blood Glucose (Gtmax) of Part A | 1.00 hour |
| 0.2 mg of LY3143753 (Part A) | PD: Time to Maximum Blood Glucose (Gtmax) of Part A | 0.67 hour |
| 0.4 mg of LY3143753 (Part A) | PD: Time to Maximum Blood Glucose (Gtmax) of Part A | 0.79 hour |
| 1 mg of LY3143753 (Part A) | PD: Time to Maximum Blood Glucose (Gtmax) of Part A | 0.58 hour |
Secondary
Pharmacodynamic (PD): Absolute Maximum Blood Glucose of Part A
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours
Population: All participants who received at least one dose of study drug or placebo and have evaluable PD data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Pharmacodynamic (PD): Absolute Maximum Blood Glucose of Part A | 101 milligram/deciliter (mg/dL) | Geometric Coefficient of Variation 10 |
| 0.05 mg of LY3143753 (Part A) | Pharmacodynamic (PD): Absolute Maximum Blood Glucose of Part A | 168 milligram/deciliter (mg/dL) | Geometric Coefficient of Variation 26 |
| 0.1 mg of LY3143753 (Part A) | Pharmacodynamic (PD): Absolute Maximum Blood Glucose of Part A | 197 milligram/deciliter (mg/dL) | Geometric Coefficient of Variation 17 |
| 0.2 mg of LY3143753 (Part A) | Pharmacodynamic (PD): Absolute Maximum Blood Glucose of Part A | 179 milligram/deciliter (mg/dL) | Geometric Coefficient of Variation 13 |
| 0.4 mg of LY3143753 (Part A) | Pharmacodynamic (PD): Absolute Maximum Blood Glucose of Part A | 188 milligram/deciliter (mg/dL) | Geometric Coefficient of Variation 10 |
| 1 mg of LY3143753 (Part A) | Pharmacodynamic (PD): Absolute Maximum Blood Glucose of Part A | 177 milligram/deciliter (mg/dL) | Geometric Coefficient of Variation 19 |
Secondary
Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of Part A
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of Part A | 0.726 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 81 |
| 0.05 mg of LY3143753 (Part A) | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of Part A | 1.05 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 73 |
| 0.1 mg of LY3143753 (Part A) | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of Part A | 2.95 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 13 |
| 0.2 mg of LY3143753 (Part A) | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of Part A | 5.73 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| 0.4 mg of LY3143753 (Part A) | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of Part A | 11.4 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
Secondary
PK: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Part A
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | PK: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Part A | 1.44 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 46 |
| 0.05 mg of LY3143753 (Part A) | PK: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Part A | 1.57 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 97 |
| 0.1 mg of LY3143753 (Part A) | PK: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Part A | 5.76 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
| 0.2 mg of LY3143753 (Part A) | PK: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Part A | 12.6 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 33 |
| 0.4 mg of LY3143753 (Part A) | PK: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Part A | 22.6 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 62 |
Secondary
PK: AUC(0-∞) of Part B
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | PK: AUC(0-∞) of Part B | NA ng*hr/mL | — |
| 0.05 mg of LY3143753 (Part A) | PK: AUC(0-∞) of Part B | 0.564 ng*hr/mL | Geometric Coefficient of Variation 8 |
| 0.1 mg of LY3143753 (Part A) | PK: AUC(0-∞) of Part B | 2.61 ng*hr/mL | Geometric Coefficient of Variation 42 |
| 0.2 mg of LY3143753 (Part A) | PK: AUC(0-∞) of Part B | 1.34 ng*hr/mL | Geometric Coefficient of Variation 24 |
| 0.4 mg of LY3143753 (Part A) | PK: AUC(0-∞) of Part B | 3.73 ng*hr/mL | Geometric Coefficient of Variation 22 |
| 1 mg of LY3143753 (Part A) | PK: AUC(0-∞) of Part B | 8.87 ng*hr/mL | Geometric Coefficient of Variation 18 |
| Placebo (Part B) | PK: AUC(0-∞) of Part B | 10.8 ng*hr/mL | Geometric Coefficient of Variation 14 |
| 0.01 mg of LY3185643 (Part B) | PK: AUC(0-∞) of Part B | 16.2 ng*hr/mL | Geometric Coefficient of Variation 55 |
| 0.03 mg of LY3185643 (Part B) | PK: AUC(0-∞) of Part B | 21.5 ng*hr/mL | Geometric Coefficient of Variation 9 |
Secondary
PK: Cmax of Part B
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | PK: Cmax of Part B | 0.126 ng/mL | Geometric Coefficient of Variation 12 |
| 0.05 mg of LY3143753 (Part A) | PK: Cmax of Part B | 0.367 ng/mL | Geometric Coefficient of Variation 51 |
| 0.1 mg of LY3143753 (Part A) | PK: Cmax of Part B | 1.19 ng/mL | Geometric Coefficient of Variation 70 |
| 0.2 mg of LY3143753 (Part A) | PK: Cmax of Part B | 0.951 ng/mL | Geometric Coefficient of Variation 32 |
| 0.4 mg of LY3143753 (Part A) | PK: Cmax of Part B | 2.34 ng/mL | Geometric Coefficient of Variation 48 |
| 1 mg of LY3143753 (Part A) | PK: Cmax of Part B | 4.25 ng/mL | Geometric Coefficient of Variation 53 |
| Placebo (Part B) | PK: Cmax of Part B | 4.67 ng/mL | Geometric Coefficient of Variation 51 |
| 0.01 mg of LY3185643 (Part B) | PK: Cmax of Part B | 6.49 ng/mL | Geometric Coefficient of Variation 58 |
| 0.03 mg of LY3185643 (Part B) | PK: Cmax of Part B | 9.67 ng/mL | Geometric Coefficient of Variation 14 |
Secondary
PK: Time to Maximum Drug Concentration (Tmax) of Part A
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Part A) | PK: Time to Maximum Drug Concentration (Tmax) of Part A | 0.67 hour |
| 0.05 mg of LY3143753 (Part A) | PK: Time to Maximum Drug Concentration (Tmax) of Part A | 0.83 hour |
| 0.1 mg of LY3143753 (Part A) | PK: Time to Maximum Drug Concentration (Tmax) of Part A | 0.67 hour |
| 0.2 mg of LY3143753 (Part A) | PK: Time to Maximum Drug Concentration (Tmax) of Part A | 1.04 hour |
| 0.4 mg of LY3143753 (Part A) | PK: Time to Maximum Drug Concentration (Tmax) of Part A | 1.25 hour |
Secondary
PK: Tmax of Part B
Time frame: Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Part A) | PK: Tmax of Part B | 0.83 hour |
| 0.05 mg of LY3143753 (Part A) | PK: Tmax of Part B | 0.67 hour |
| 0.1 mg of LY3143753 (Part A) | PK: Tmax of Part B | 0.83 hour |
| 0.2 mg of LY3143753 (Part A) | PK: Tmax of Part B | 0.67 hour |
| 0.4 mg of LY3143753 (Part A) | PK: Tmax of Part B | 0.50 hour |
| 1 mg of LY3143753 (Part A) | PK: Tmax of Part B | 1.25 hour |
| Placebo (Part B) | PK: Tmax of Part B | 1.23 hour |
| 0.01 mg of LY3185643 (Part B) | PK: Tmax of Part B | 1.75 hour |
| 0.03 mg of LY3185643 (Part B) | PK: Tmax of Part B | 0.83 hour |
Secondary
QTcF Change From Baseline of Part B
Time frame: Baseline, 8 hours after drug administration
Population: All randomized participants who received at least one dose of study drug and had evaluable QTcF data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | QTcF Change From Baseline of Part B | -1.4 milliseconds (msec) | Standard Deviation 8.3 |
| 0.05 mg of LY3143753 (Part A) | QTcF Change From Baseline of Part B | -2.9 milliseconds (msec) | Standard Deviation 8.5 |
| 0.1 mg of LY3143753 (Part A) | QTcF Change From Baseline of Part B | -10.2 milliseconds (msec) | Standard Deviation 3.3 |
| 0.2 mg of LY3143753 (Part A) | QTcF Change From Baseline of Part B | -5.9 milliseconds (msec) | Standard Deviation 12.5 |
| 0.4 mg of LY3143753 (Part A) | QTcF Change From Baseline of Part B | -4.1 milliseconds (msec) | Standard Deviation 7.8 |
| 1 mg of LY3143753 (Part A) | QTcF Change From Baseline of Part B | 0.5 milliseconds (msec) | Standard Deviation 11.3 |
| Placebo (Part B) | QTcF Change From Baseline of Part B | -4.7 milliseconds (msec) | Standard Deviation 7.6 |
| 0.01 mg of LY3185643 (Part B) | QTcF Change From Baseline of Part B | 2.5 milliseconds (msec) | Standard Deviation 13 |
| 0.03 mg of LY3185643 (Part B) | QTcF Change From Baseline of Part B | -2.1 milliseconds (msec) | Standard Deviation 2.7 |
| 0.05 mg of LY3185643 (Part B) | QTcF Change From Baseline of Part B | NA milliseconds (msec) | — |
| 0.06 mg of LY3185643 (Part B) | QTcF Change From Baseline of Part B | -7.7 milliseconds (msec) | Standard Deviation 5.8 |
Secondary
QT Interval as Corrected by the Fridericia Method (QTcF) Change From Baseline of Part A
Time frame: Baseline, 8 hours after drug administration
Population: All randomized participants who received at least one dose of study drug and who had evaluable QTcF data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | QT Interval as Corrected by the Fridericia Method (QTcF) Change From Baseline of Part A | 0.6 milliseconds (msec) | Standard Deviation 6.4 |
| 0.05 mg of LY3143753 (Part A) | QT Interval as Corrected by the Fridericia Method (QTcF) Change From Baseline of Part A | NA milliseconds (msec) | — |
| 0.1 mg of LY3143753 (Part A) | QT Interval as Corrected by the Fridericia Method (QTcF) Change From Baseline of Part A | 0.2 milliseconds (msec) | Standard Deviation 18.6 |
| 0.2 mg of LY3143753 (Part A) | QT Interval as Corrected by the Fridericia Method (QTcF) Change From Baseline of Part A | NA milliseconds (msec) | — |
| 0.4 mg of LY3143753 (Part A) | QT Interval as Corrected by the Fridericia Method (QTcF) Change From Baseline of Part A | 6.1 milliseconds (msec) | Standard Deviation 14.5 |
| 1 mg of LY3143753 (Part A) | QT Interval as Corrected by the Fridericia Method (QTcF) Change From Baseline of Part A | 6.1 milliseconds (msec) | Standard Deviation 13.3 |