Healthy
Conditions
Brief summary
The purpose of this study is to look at the amount of the study drug, LY3074828, that gets into the blood stream and how long it takes the body to get rid of LY3074828 when given as different formulations. The tolerability of LY3074828 will also be evaluated and information about any side effects experienced will be collected. Screening is required within 28 days prior to the start of the study. For each participant, the total duration of the clinical trial will be approximately 13 weeks, not including screening.
Interventions
BIOLOGICALLY3074828
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Exclusion criteria
* Must not have an average weekly alcohol intake that exceeds 21 units/week (males) and 14 units/week (females) * Must not show evidence of active or latent tuberculosis (TB) * Must not have received live vaccine(s) (including attenuated live vaccines and those administered intranasally) within 1 month of screening, or intend to during the study * Must not have been treated with steroids within 1 month of screening, or intend to during the study * Must not be immunocompromised * Must not have received treatment with biologic agents (e.g. monoclonal antibodies, including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to Day 1 * Must not have significant allergies to humanised monoclonal antibodies * Must not have clinically significant multiple or severe drug allergies, or intolerance to topical corticosteroids, or sever post treatment hypersensitivity reactions * Must not have had lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years * Must not have had breast cancer within the past 10 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (DN-AUC[0-tlast]) of LY3074828 | Predose; 2, 6, 24, 72, 168, 240, 336, 504, 672, 1008, 1344, 1680 and 2016 hours postdose | PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (DN-AUC\[0-tlast\]) of LY3074828 was evaluated. Unit of measure expansion: microgram\*day per milliliter per milligram (µg\*day/mL/mg). |
| PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (DN-AUC[0-∞]) of LY3074828 | Predose; 2, 6, 24, 72, 168, 240, 336, 504, 672, 1008, 1344, 1680 and 2016 hours postdose | PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (DN-AUC\[0-∞\]) of LY3074828 was evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) | Predose Day 1 Through Day 85 | Number of participants with positive treatment emergent anti-drug antibodies was summarized by treatment group. A treatment-emergent ADA (TEADA) was defined as: having a negative ADA at baseline and an ADA titer greater than or equal to 1:20 (that is (i.e.), greater than 2-fold from the minimal required dilution of 1:10) any time post baseline (i.e., treatment-induced); or a 4-fold or greater change in ADA titer from baseline for participants that had a detectable ADA titer at baseline (i.e., treatment boosted). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Reference: 250 mg LY3074828 Participants received 250 mg LY3074828 lyophilized formulation, as 3 SC injections | 18 |
| Test 1: 250 mg LY3074828 Participants received 250 mg LY3074828 solution formulation in 2 PFSs, as SC injections | 18 |
| Test 2: 500 mg LY3074828 Participants received 500 mg LY3074828 solution formulation in 4 PFSs, as SC injections | 18 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Inappropriate behavior with site staff | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Test 1: 250 mg LY3074828 | Total | Reference: 250 mg LY3074828 | Test 2: 500 mg LY3074828 |
|---|---|---|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 11 | 42.0 years STANDARD_DEVIATION 11.1 | 41.6 years STANDARD_DEVIATION 12.6 | 42.5 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 14 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 40 Participants | 14 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 26 Participants | 9 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 26 Participants | 9 Participants | 9 Participants |
| Region of Enrollment United States | 18 Participants | 54 Participants | 18 Participants | 18 Participants |
| Sex: Female, Male Female | 8 Participants | 26 Participants | 10 Participants | 8 Participants |
| Sex: Female, Male Male | 10 Participants | 28 Participants | 8 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 16 / 18 | 15 / 18 | 18 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Pharmacokinetics (PK): Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (DN-AUC[0-tlast]) of LY3074828
PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (DN-AUC\[0-tlast\]) of LY3074828 was evaluated. Unit of measure expansion: microgram\*day per milliliter per milligram (µg\*day/mL/mg).
Time frame: Predose; 2, 6, 24, 72, 168, 240, 336, 504, 672, 1008, 1344, 1680 and 2016 hours postdose
Population: All enrolled participants who received at least one dose of LY3074828 and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference: 250 mg LY3074828 | Pharmacokinetics (PK): Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (DN-AUC[0-tlast]) of LY3074828 | 1.06 µg*day/mL/mg | Geometric Coefficient of Variation 27 |
| Test 1: 250 mg LY3074828 | Pharmacokinetics (PK): Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (DN-AUC[0-tlast]) of LY3074828 | 1.03 µg*day/mL/mg | Geometric Coefficient of Variation 40 |
| Test 2: 500 mg LY3074828 | Pharmacokinetics (PK): Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (DN-AUC[0-tlast]) of LY3074828 | 1.04 µg*day/mL/mg | Geometric Coefficient of Variation 32 |
90% CI: [0.805, 1.17]
90% CI: [0.841, 1.22]
90% CI: [0.819, 1.18]
Primary
PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (DN-AUC[0-∞]) of LY3074828
PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (DN-AUC\[0-∞\]) of LY3074828 was evaluated.
Time frame: Predose; 2, 6, 24, 72, 168, 240, 336, 504, 672, 1008, 1344, 1680 and 2016 hours postdose
Population: All enrolled participants who received at least one dose of LY3074828 and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference: 250 mg LY3074828 | PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (DN-AUC[0-∞]) of LY3074828 | 1.07 µg.day/mL/mg | Geometric Coefficient of Variation 27 |
| Test 1: 250 mg LY3074828 | PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (DN-AUC[0-∞]) of LY3074828 | 1.05 µg.day/mL/mg | Geometric Coefficient of Variation 40 |
| Test 2: 500 mg LY3074828 | PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (DN-AUC[0-∞]) of LY3074828 | 1.05 µg.day/mL/mg | Geometric Coefficient of Variation 32 |
90% CI: [0.811, 1.18]
90% CI: [0.833, 1.21]
90% CI: [0.817, 1.18]
Secondary
Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA)
Number of participants with positive treatment emergent anti-drug antibodies was summarized by treatment group. A treatment-emergent ADA (TEADA) was defined as: having a negative ADA at baseline and an ADA titer greater than or equal to 1:20 (that is (i.e.), greater than 2-fold from the minimal required dilution of 1:10) any time post baseline (i.e., treatment-induced); or a 4-fold or greater change in ADA titer from baseline for participants that had a detectable ADA titer at baseline (i.e., treatment boosted).
Time frame: Predose Day 1 Through Day 85
Population: All randomized participants who received at least one dose of LY3074828 and had evaluable anti-drug antibody measurement.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reference: 250 mg LY3074828 | Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) | 7 Participants |
| Test 1: 250 mg LY3074828 | Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) | 6 Participants |
| Test 2: 500 mg LY3074828 | Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) | 7 Participants |