Healthy
Conditions
Brief summary
This study evaluates a new formulation of ramucirumab, a drug approved for several types of cancer. In this study of healthy participants, a small amount of ramucirumab will be given by injection either into a vein or just under the skin. Study doctors will measure the amount of ramucirumab in the bloodstream. Side effects and tolerability will be documented. The study will last for about 16 weeks for each participant, including screening and follow up. Screening is required within 28 days prior to entering the study.
Interventions
DRUGRamucirumab - IV
Administered IV.
DRUGPlacebo - IV
Administered IV.
DRUGRamucirumab - SC
Administered SC.
DRUGPlacebo - SC
Administered SC.
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 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy male or a female (not pregnant and agreeable to take birth control measures until study completion) * Have a body weight greater than or equal to (≥)70 kilograms (kg) and body mass index (BMI) of 18 to 32 kilogram per square meter (kg/m ²), inclusive * Have normal blood pressure, pulse rate, electrocardiogram (ECG), and blood and urine laboratory test results that are acceptable for the study
Exclusion criteria
* Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study * Have previously participated or withdrawn from this study * Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study * Had blood loss of more than 500 milliliters (mL) within the previous 30 days of study screening
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 90 | An SAE is any adverse event from this study that results in 1 of the following: Death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, risk of death), persistent or significant disability/incapacity, congenital anomaly/birth defect, Important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent 1 of the other outcomes listed in the definition above. The number of participants with one or more SAEs considered by the investigator to be related to study drug administration is reported. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module |
| Number of Participants With Injection Site Reactions (ISRs) Following Subcutaneous (SC) Administration of Study Drug | Day 1 Predose through Day 90 | Number of participants showing ISRs when the drug was administered subcutaneously were reported. |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Ramucirumab | 1, 8, 24, 48, 72, 96, 120, 144, 168, 264, 336, 504 hours post-dose | PK: AUC\[0-∞\] of Ramucirumab. |
| PK: Maximum Concentration (Cmax) of Ramucirumab | 1, 8, 24, 48, 72, 96, 120, 144, 168, 264, 336, 504 hours post-dose | PK: Cmax of Ramucirumab |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo IV Participants received single dose of placebo administered IV. | 3 |
| 350 mg Ramucirumab IV Participants received single 350 mg ramucirumab administered as a 60-minute intravenous infusion at a concentration of 10 mg/mL as one 35 mL infusion. | 7 |
| Placebo SC Participants received single dose of placebo administered SC. | 12 |
| 350 mg Ramucirumab SC (1x2 mL) Participants received single 350 mg ramucirumab SC administered at a concentration of 175 mg/mL as one 2 mL injection. | 7 |
| 350 mg Ramucirumab SC (2x2 mL) Participants received single 350 mg ramucirumab SC administered at a concentration of 87.5 mg/mL as two 2 mL injections. | 7 |
| 350 mg Ramucirumab SC (2x1 mL) Participants received single 350 mg ramucirumab SC administered at a concentration of 175 mg/mL as two 1 mL injections. | 7 |
| 700 mg Ramucirumab SC (2x2 mL) Participants received single 700 mg ramucirumab SC administered at a concentration of 175 mg/mL as two 2 mL injections. | 7 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo IV | Total | 700 mg Ramucirumab SC (2x2 mL) | 350 mg Ramucirumab SC (2x1 mL) | 350 mg Ramucirumab SC (2x2 mL) | 350 mg Ramucirumab SC (1x2 mL) | Placebo SC | 350 mg Ramucirumab IV |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 34 years | 40 years | 41 years | 39 years | 46 years | 51 years | 37 years | 35 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 23 Participants | 1 Participants | 2 Participants | 4 Participants | 4 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 27 Participants | 6 Participants | 5 Participants | 3 Participants | 3 Participants | 5 Participants | 4 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 | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 12 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 2 Participants | 35 Participants | 5 Participants | 5 Participants | 5 Participants | 6 Participants | 8 Participants | 4 Participants |
| Region of Enrollment United States | 3 Participants | 50 Participants | 7 Participants | 7 Participants | 7 Participants | 7 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 9 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 41 Participants | 6 Participants | 7 Participants | 5 Participants | 5 Participants | 10 Participants | 5 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 | 0 / 3 | 0 / 7 | 0 / 12 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 1 / 3 | 4 / 7 | 1 / 12 | 3 / 7 | 2 / 7 | 5 / 7 | 4 / 7 |
| serious Total, serious adverse events | 0 / 3 | 0 / 7 | 1 / 12 | 0 / 7 | 1 / 7 | 0 / 7 | 0 / 7 |
Outcome results
Primary
Number of Participants With Injection Site Reactions (ISRs) Following Subcutaneous (SC) Administration of Study Drug
Number of participants showing ISRs when the drug was administered subcutaneously were reported.
Time frame: Day 1 Predose through Day 90
Population: All participants who received at least one dose of study drug subcutaneously.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo IV | Number of Participants With Injection Site Reactions (ISRs) Following Subcutaneous (SC) Administration of Study Drug | 3 Participants |
| 350 mg Ramucirumab IV | Number of Participants With Injection Site Reactions (ISRs) Following Subcutaneous (SC) Administration of Study Drug | 3 Participants |
| Placebo SC | Number of Participants With Injection Site Reactions (ISRs) Following Subcutaneous (SC) Administration of Study Drug | 2 Participants |
| 350 mg Ramucirumab SC (1x2 mL) | Number of Participants With Injection Site Reactions (ISRs) Following Subcutaneous (SC) Administration of Study Drug | 1 Participants |
| 350 mg Ramucirumab SC (2x2 mL) | Number of Participants With Injection Site Reactions (ISRs) Following Subcutaneous (SC) Administration of Study Drug | 1 Participants |
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
An SAE is any adverse event from this study that results in 1 of the following: Death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, risk of death), persistent or significant disability/incapacity, congenital anomaly/birth defect, Important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent 1 of the other outcomes listed in the definition above. The number of participants with one or more SAEs considered by the investigator to be related to study drug administration is reported. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module
Time frame: Baseline through Day 90
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo IV | 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 |
| 350 mg Ramucirumab IV | 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 SC | 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 |
| 350 mg Ramucirumab SC (1x2 mL) | 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 |
| 350 mg Ramucirumab SC (2x2 mL) | 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 |
| 350 mg Ramucirumab SC (2x1 mL) | 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 |
| 700 mg Ramucirumab SC (2x2 mL) | 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 |
Primary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Ramucirumab
PK: AUC\[0-∞\] of Ramucirumab.
Time frame: 1, 8, 24, 48, 72, 96, 120, 144, 168, 264, 336, 504 hours post-dose
Population: All participants who received at least one dose of ramucirumab and had sufficient evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Ramucirumab | 18700 hour*microgram per milliliter (h*μg/mL) | Geometric Coefficient of Variation 19 |
| 350 mg Ramucirumab IV | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Ramucirumab | 5250 hour*microgram per milliliter (h*μg/mL) | Geometric Coefficient of Variation 48 |
| Placebo SC | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Ramucirumab | 5140 hour*microgram per milliliter (h*μg/mL) | Geometric Coefficient of Variation 76 |
| 350 mg Ramucirumab SC (1x2 mL) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Ramucirumab | 6350 hour*microgram per milliliter (h*μg/mL) | Geometric Coefficient of Variation 57 |
| 350 mg Ramucirumab SC (2x2 mL) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Ramucirumab | 14200 hour*microgram per milliliter (h*μg/mL) | Geometric Coefficient of Variation 76 |
Primary
PK: Maximum Concentration (Cmax) of Ramucirumab
PK: Cmax of Ramucirumab
Time frame: 1, 8, 24, 48, 72, 96, 120, 144, 168, 264, 336, 504 hours post-dose
Population: All participants who received at least one dose of ramucirumab and had sufficient evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | PK: Maximum Concentration (Cmax) of Ramucirumab | 116 μg/mL | Geometric Coefficient of Variation 11 |
| 350 mg Ramucirumab IV | PK: Maximum Concentration (Cmax) of Ramucirumab | 24 μg/mL | Geometric Coefficient of Variation 56 |
| Placebo SC | PK: Maximum Concentration (Cmax) of Ramucirumab | 20.2 μg/mL | Geometric Coefficient of Variation 63 |
| 350 mg Ramucirumab SC (1x2 mL) | PK: Maximum Concentration (Cmax) of Ramucirumab | 21 μg/mL | Geometric Coefficient of Variation 66 |
| 350 mg Ramucirumab SC (2x2 mL) | PK: Maximum Concentration (Cmax) of Ramucirumab | 46.7 μg/mL | Geometric Coefficient of Variation 44 |