Migraine Disorders
Conditions
Brief summary
The main purpose of this study is to evaluate the safety of the study drug known as LY2951742 in healthy Japanese and Caucasians. The study will also investigate how the body processes the drug and how the drug affects the body. The study is expected to last about 5 to 7 months, depending on the arm.
Interventions
DRUGLY2951742
Administered subcutaneously.
DRUGPlacebo
Administered subcutaneously.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants are either Caucasian or first generation Japanese. * Participants' body mass index (BMI) is between 18.0 and 35.0 kilogram per meter square (kg/ m\^2).
Exclusion criteria
* Participants are heavy caffeine drinkers defined by regular intake of more than 5 cups of coffee (or equivalent in xanthine containing beverages) per day, and/or are unable or unwilling to abide by caffeine restrictions as specified in the protocol. * Participants are smoking within the previous 6 months. * Participants have received treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) prior to dosing or have received a vaccination within 1 month. * Participants have known allergies to LY2951742, related compounds or any components of the formulation, or history of significant atopy. * Participants are allergies to either humanized monoclonal antibodies, diphenhydramine, epinephrine, or methylprednisolone.
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 through Day 197 | A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2951742 | Day 1: Predose, 8 hr and 24 hour postdose | Cmax was evaluated to delineate dose proportionality for the dose cohorts using a power model for geometric means and coefficient of variation. Statistical analysis was not prespecified. |
| Pharmacokinetics (PK): Area Under the Concentration Curve, Zero to Infinity ( AUC[0-∞]) | Day 1: Predose, 8 hr and 24 hour postdose | AUC was evaluated to delineate dose proportionality for the dose cohorts using a power model for geometric means and coefficient of variation. Statistical analysis was not prespecified. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (SD) 1 subcutaneous (SC) dose of placebo | 8 |
| 5 mg LY2951742 Single Dose (SD) 1 SC dose of 5 mg LY2951742 | 6 |
| 50 mg LY2951742 (SD) 1 SC dose of 50 mg LY2951742 | 6 |
| 120 mg LY2951742 (SD) 1 SC dose of 120 mg LY2951742 | 7 |
| 300 mg LY2951742 (SD) 1 SC dose of 300 mg LY2951742. | 8 |
| Placebo Q4W 3 SC doses of placebo every 4 Weeks (Q4W) | 2 |
| 300 mg LY2951742 Q4W 3 SC doses of 300 mg LY2951742 Q4W | 8 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | 300 mg LY2951742 Q4W | Placebo (SD) | 5 mg LY2951742 Single Dose (SD) | Total | 50 mg LY2951742 (SD) | 120 mg LY2951742 (SD) | 300 mg LY2951742 (SD) | Placebo Q4W |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 11 | 43.9 years STANDARD_DEVIATION 11.6 | 38.8 years STANDARD_DEVIATION 9.9 | 40.0 years STANDARD_DEVIATION 11 | 42.7 years STANDARD_DEVIATION 12.2 | 34.6 years STANDARD_DEVIATION 11 | 35.5 years STANDARD_DEVIATION 10.3 | NA years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 8 Participants | 6 Participants | 42 Participants | 6 Participants | 6 Participants | 8 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 3 Participants | 25 Participants | 3 Participants | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 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 |
| 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 3 Participants | 20 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants |
| Region of Enrollment United States | 8 Participants | 8 Participants | 6 Participants | 45 Participants | 6 Participants | 7 Participants | 8 Participants | 2 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 3 Participants | 19 Participants | 1 Participants | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 3 Participants | 26 Participants | 5 Participants | 5 Participants | 5 Participants | 1 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 8 | 5 / 6 | 5 / 6 | 6 / 7 | 8 / 8 | 2 / 2 | 7 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 8 | 0 / 2 | 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 AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section
Time frame: Baseline through Day 197
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (SD) | 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 |
| 5 mg LY2951742 Single Dose (SD) | 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 |
| 50 mg LY2951742 (SD) | 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 |
| 120 mg LY2951742 (SD) | 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 |
| 300 mg LY2951742 (SD) | 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 |
| Placebo Q4W | 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 |
| 300 mg LY2951742 Q4W | 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
Pharmacokinetics (PK): Area Under the Concentration Curve, Zero to Infinity ( AUC[0-∞])
AUC was evaluated to delineate dose proportionality for the dose cohorts using a power model for geometric means and coefficient of variation. Statistical analysis was not prespecified.
Time frame: Day 1: Predose, 8 hr and 24 hour postdose
Population: All participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (SD) | Pharmacokinetics (PK): Area Under the Concentration Curve, Zero to Infinity ( AUC[0-∞]) | 27600 ng*hr/mL | Geometric Coefficient of Variation 24 |
| 5 mg LY2951742 Single Dose (SD) | Pharmacokinetics (PK): Area Under the Concentration Curve, Zero to Infinity ( AUC[0-∞]) | 173000 ng*hr/mL | Geometric Coefficient of Variation 51 |
| 50 mg LY2951742 (SD) | Pharmacokinetics (PK): Area Under the Concentration Curve, Zero to Infinity ( AUC[0-∞]) | 733000 ng*hr/mL | Geometric Coefficient of Variation 38 |
| 120 mg LY2951742 (SD) | Pharmacokinetics (PK): Area Under the Concentration Curve, Zero to Infinity ( AUC[0-∞]) | 1520000 ng*hr/mL | Geometric Coefficient of Variation 33 |
| 300 mg LY2951742 (SD) | Pharmacokinetics (PK): Area Under the Concentration Curve, Zero to Infinity ( AUC[0-∞]) | 757000 ng*hr/mL | Geometric Coefficient of Variation 41 |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2951742
Cmax was evaluated to delineate dose proportionality for the dose cohorts using a power model for geometric means and coefficient of variation. Statistical analysis was not prespecified.
Time frame: Day 1: Predose, 8 hr and 24 hour postdose
Population: All participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (SD) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2951742 | 775 nanogram/millliliter (ng/mL) | Geometric Coefficient of Variation 27 |
| 5 mg LY2951742 Single Dose (SD) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2951742 | 4270 nanogram/millliliter (ng/mL) | Geometric Coefficient of Variation 58 |
| 50 mg LY2951742 (SD) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2951742 | 18000 nanogram/millliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| 120 mg LY2951742 (SD) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2951742 | 41400 nanogram/millliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| 300 mg LY2951742 (SD) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2951742 | 36300 nanogram/millliliter (ng/mL) | Geometric Coefficient of Variation 42 |