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 a solution formulation in different devices. 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
Inclusion criteria
\- Must be healthy male or female
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 |
|---|---|---|
| Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3074828 | Day 1: 0, 2, 6; Day 2: 24; Day 4: 72; Day 8: 168; Day 11: 240; Day 15: 336; Day 22: 504; Day 29: 672; Day 43: 1008; Day 57: 1344; Day 71: 1680; Day 85: 2016 hours | Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3074828 |
| Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3074828 | Day 1: 0, 2, 6; Day 2: 24; Day 4: 72; Day 8: 168; Day 11: 240; Day 15: 336; Day 22: 504; Day 29: 672; Day 43: 1008; Day 57: 1344; Day 71: 1680; Day 85: 2016 hours | Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC\[0-inf\]) of LY3074828 |
| Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3074828 | Day 1: 0, 2, 6; Day 2: 24; Day 4: 72; Day 8: 168; Day 11: 240; Day 15: 336; Day 22: 504; Day 29: 672; Day 43: 1008; Day 57: 1344; Day 71: 1680; Day 85: 2016 hours | Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to tlast (AUC\[0-tlast\]) of LY3074828 |
| Part A: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including Visual Analog Scale (VAS ) Score) | Day 1, 0 hour | Pain was assessed by the SF-MPQ and quantified using the validated VAS where 0mm represented no pain and 100mm represented worst possible pain. The SF-MPQ total score ranges from 0 to 45 (the higher the total score, the more pain experienced). Least Squares (LS) mean was calculated using linear fixed-effects model with treatment (Reference or Test 1) as a fixed effect. Model: Log (Score+1) = Treatment + Random Error. |
| Part B: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including VAS Score) For 250 mg LY3074828 Slow Versus Fast | Day 1, 0 hour | Pain was assessed by the SF-MPQ and quantified using the validated VAS where 0mm represented no pain and 100mm represented worst possible pain. The SF-MPQ total score ranges from 0 to 45 (the higher the total score, the more pain experienced). LS mean was calculated using linear fixed-effects model with treatment (Test 2 or Test 3) as a fixed effect. Model: Log (Score+1) = Treatment + Random Error. |
| Part B: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including VAS Score) For 125 mg LY3074828 Slow Versus Fast | Day 1, 0 hour | Pain was assessed by the SF-MPQ and quantified using the validated VAS where 0mm represented no pain and 100mm represented worst possible pain. The SF-MPQ total score ranges from 0 to 45 (the higher the total score, the more pain experienced). LS mean was calculated using linear fixed-effects model with treatment (Test 4 or Test 5) as a fixed effect. Model: Log (Score+1) = Treatment + Random Error. |
Countries
United States
Participant flow
Pre-assignment details
This study had a screening period of 28 days and residential period with a parallel 2 day Part A and a crossover 3 day Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: 250 mg LY3074828 (Reference) 250 mg LY3074828 administered subcutaneous (SC) as solution formulation in two prefilled syringes targeting a 5- to 10-second injection time for each injection on day 1. | 18 |
| Part A: 250 mg LY3074828 (Test 1) 250 mg LY3074828 administered SC as solution formulation in a prefilled syringe targeting a 5- to 15-second injection time on day 1. | 18 |
| Part B: 250 mg LY3074828 (Test 2 and Test 3) Test 2: 250 mg LY3074828 administered subcutaneous (SC) as solution formulation in an auto-injector at slow speed targeting an approximately 13-second injection time on day 1
Test 3: 250 mg LY3074828 administered subcutaneous (SC) as solution formulation in an auto-injector at fast speed targeting an approximately 5-second injection time on day 2 | 18 |
| Part B: 125 mg LY3074828 (Test 4 and Test 5) Test 4: 125 mg LY3074828 administered SC as solution formulation in an auto-injector at slow speed targeting an approximately 7-second injection time on day 1
Test 5: 125 mg LY3074828 administered SC as solution formulation in an auto-injector at fast speed targeting an approximately 4.5-second injection time on day 2. | 18 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part A: 250 mg LY3074828 (Reference) | Part B: 250 mg LY3074828 (Test 2 and Test 3) | Part B: 125 mg LY3074828 (Test 4 and Test 5) | Part A: 250 mg LY3074828 (Test 1) |
|---|---|---|---|---|---|
| Age, Continuous Part A | 35.6 years STANDARD_DEVIATION 11.8 | 37.3 years STANDARD_DEVIATION 12.7 | NA years | NA years | 33.9 years STANDARD_DEVIATION 11 |
| Age, Continuous Part B | 44.7 years STANDARD_DEVIATION 12.4 | NA years | 42.1 years STANDARD_DEVIATION 12.3 | 47.2 years STANDARD_DEVIATION 12.3 | NA years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 6 Participants | 3 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 12 Participants | 15 Participants | 12 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 8 Participants | 6 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 10 Participants | 10 Participants | 10 Participants | 10 Participants |
| Region of Enrollment United States | 72 Participants | 18 Participants | 18 Participants | 18 Participants | 18 Participants |
| Sex: Female, Male Female | 33 Participants | 9 Participants | 8 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 39 Participants | 9 Participants | 10 Participants | 12 Participants | 8 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 2 / 18 | 6 / 18 | 1 / 18 | 5 / 18 | 1 / 18 | 1 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3074828
Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3074828
Time frame: Day 1: 0, 2, 6; Day 2: 24; Day 4: 72; Day 8: 168; Day 11: 240; Day 15: 336; Day 22: 504; Day 29: 672; Day 43: 1008; Day 57: 1344; Day 71: 1680; Day 85: 2016 hours
Population: Part A: All randomized participants who received at least one dose of LY3074828 and have evaluable PK data. Per protocol only Part A data were analyzed for PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: 250 mg LY3074828 (Reference) | Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3074828 | 14.4 microgram per milliliters (μg/mL) | Geometric Coefficient of Variation 67 |
| Part A: 250 mg LY3074828 (Test 1) | Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3074828 | 21.1 microgram per milliliters (μg/mL) | Geometric Coefficient of Variation 34 |
90% CI: [1.12, 1.94]
Primary
Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3074828
Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC\[0-inf\]) of LY3074828
Time frame: Day 1: 0, 2, 6; Day 2: 24; Day 4: 72; Day 8: 168; Day 11: 240; Day 15: 336; Day 22: 504; Day 29: 672; Day 43: 1008; Day 57: 1344; Day 71: 1680; Day 85: 2016 hours
Population: All randomized participants who received at least one dose of LY3074828 and have evaluable PK data in Part A. Per protocol only Part A data were analyzed for PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: 250 mg LY3074828 (Reference) | Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3074828 | 240 Microgram*Day per Milliliters(μg*day/mL) | Geometric Coefficient of Variation 46 |
| Part A: 250 mg LY3074828 (Test 1) | Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3074828 | 346 Microgram*Day per Milliliters(μg*day/mL) | Geometric Coefficient of Variation 33 |
90% CI: [1.15, 1.81]
Primary
Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3074828
Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to tlast (AUC\[0-tlast\]) of LY3074828
Time frame: Day 1: 0, 2, 6; Day 2: 24; Day 4: 72; Day 8: 168; Day 11: 240; Day 15: 336; Day 22: 504; Day 29: 672; Day 43: 1008; Day 57: 1344; Day 71: 1680; Day 85: 2016 hours
Population: All randomized participants who received at least one dose of LY3074828 and have evaluable PK data in Part A. Per protocol only Part A data were analyzed for PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: 250 mg LY3074828 (Reference) | Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3074828 | 205 Microgram*Day per Milliliters(μg*day/mL) | Geometric Coefficient of Variation 54 |
| Part A: 250 mg LY3074828 (Test 1) | Part A PK: Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC[0-tlast]) of LY3074828 | 341 Microgram*Day per Milliliters(μg*day/mL) | Geometric Coefficient of Variation 33 |
90% CI: [1.31, 2.11]
Primary
Part A: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including Visual Analog Scale (VAS ) Score)
Pain was assessed by the SF-MPQ and quantified using the validated VAS where 0mm represented no pain and 100mm represented worst possible pain. The SF-MPQ total score ranges from 0 to 45 (the higher the total score, the more pain experienced). Least Squares (LS) mean was calculated using linear fixed-effects model with treatment (Reference or Test 1) as a fixed effect. Model: Log (Score+1) = Treatment + Random Error.
Time frame: Day 1, 0 hour
Population: All participants who received a dose of LY3074828 whether or not they completed all protocol requirements.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: 250 mg LY3074828 (Reference) | Part A: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including Visual Analog Scale (VAS ) Score) | 4.16 units on a scale |
| Part A: 250 mg LY3074828 (Test 1) | Part A: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including Visual Analog Scale (VAS ) Score) | 3.04 units on a scale |
90% CI: [0.43, 1.23]
Primary
Part B: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including VAS Score) For 125 mg LY3074828 Slow Versus Fast
Pain was assessed by the SF-MPQ and quantified using the validated VAS where 0mm represented no pain and 100mm represented worst possible pain. The SF-MPQ total score ranges from 0 to 45 (the higher the total score, the more pain experienced). LS mean was calculated using linear fixed-effects model with treatment (Test 4 or Test 5) as a fixed effect. Model: Log (Score+1) = Treatment + Random Error.
Time frame: Day 1, 0 hour
Population: All participants who received a dose of LY3074828 whether or not they completed all protocol requirements.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: 250 mg LY3074828 (Reference) | Part B: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including VAS Score) For 125 mg LY3074828 Slow Versus Fast | 4.36 units on a scale |
| Part A: 250 mg LY3074828 (Test 1) | Part B: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including VAS Score) For 125 mg LY3074828 Slow Versus Fast | 3.07 units on a scale |
90% CI: [0.41, 1.2]
Primary
Part B: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including VAS Score) For 250 mg LY3074828 Slow Versus Fast
Pain was assessed by the SF-MPQ and quantified using the validated VAS where 0mm represented no pain and 100mm represented worst possible pain. The SF-MPQ total score ranges from 0 to 45 (the higher the total score, the more pain experienced). LS mean was calculated using linear fixed-effects model with treatment (Test 2 or Test 3) as a fixed effect. Model: Log (Score+1) = Treatment + Random Error.
Time frame: Day 1, 0 hour
Population: All participants who received a dose of LY3074828 whether or not they completed all protocol requirements.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: 250 mg LY3074828 (Reference) | Part B: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including VAS Score) For 250 mg LY3074828 Slow Versus Fast | 5.06 units on a scale |
| Part A: 250 mg LY3074828 (Test 1) | Part B: Short Form McGill Pain Questionnaire (SF-MPQ) Total Score (Including VAS Score) For 250 mg LY3074828 Slow Versus Fast | 4.96 units on a scale |
90% CI: [0.58, 1.67]