Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to investigate the safety and tolerability of LY3016859 administered as single doses, and to determine how long LY3016859 remains in the body
Interventions
DRUGLY3016859 intravenous
Administered intravenously
Administered intravenously
DRUGLY3016859 subcutaneous
Administered subcutaneously
Administered subcutaneously
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy men and women of non-childbearing potential as determined by medical history and physical examination (PE), and: * Men agree to use 2 medically accepted methods of contraception with all sexual partners during the study and for 90 days after the final dose * Women are not of child-bearing potential due to surgical sterilization (at least 6 weeks after surgical bilateral oophorectomy with or without hysterectomy or at least 6 weeks after tubal ligation) confirmed by medical history, or post-menopause. Post-menopausal status will be defined as a woman 45 years of age or older with either 12 months of spontaneous amenorrhea, or 6-12 months of spontaneous amenorrhea combined with follicle stimulating hormone (FSH) greater than (\>) 40 international units per liter (IU/L) * Are reliable and are willing to make themselves available for the duration of the study, and are willing to follow site specific study procedures * Must weigh greater than or equal to (≥) 50 kilograms (kg) at time of screening and dosing * Have clinical laboratory test results within normal reference range for the investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator * Have venous access sufficient to allow blood sampling as per the protocol * Must be a non-smoker
Exclusion criteria
* Are currently enrolled in, or have discontinued within the last 60 days from a clinical trial involving an investigational drug that has not received regulatory approval for any indication, or have received treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives of the administered drug (whichever is longer) prior to dosing * Have previously completed or withdrawn from this study or any other study investigating LY3016859, and have previously received the investigational product * Have a history or presence of medical illness including but not limited to any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric or neurological disease, or any clinically significant laboratory abnormality, that in the judgment of the investigator indicates a medical problem that would preclude study participation * Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study or have: * Confirmed corrected QT interval using Fridericia's formula (QTcF) \> 450 milliseconds (msec) for men and \> 470 msec for women * Bundle branch blocks or other conduction abnormalities other than mild first-degree atrio-ventricular block * Irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular ectopic beats * History of unexplained syncope * Family history of unexplained sudden death or sudden death due to long QT syndrome * T-wave configurations are not of sufficient quality for assessing QT interval, as determined by the investigator * Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies, hepatitis C and/or positive hepatitis C antibody, or Hepatitis B and/or positive Hepatitis B surface antigen * Show use of any medication with potential to mask allergic response for example (e.g.) antihistamines, systemic glucocorticoids or antipyretic agents) within 3 days of dosing (Note: Acetaminophen or nonsteroidal analgesics for headache may be allowed as needed in the Investigator's judgment. The following medications are also specifically allowed in this study: vitamins at normal replacement doses, hormone replacement therapies e.g. estrogen, thyroid hormone), topical medications with limited systemic effects (e.g. eye drops, skin creams, vaginal antifungals, hemorrhoid preparations, etcetera (etc.), stable preventive therapies for hyperlipidemia and gastric acidity disorders) * Have donated blood of more than 500 milliliters (mL) within the last month. * Have an average weekly alcohol intake that exceeds 21 units per week or are unwilling to stop alcohol within 48 hours of entry into study and for the duration of the study \[1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits\] * Have an abnormal blood pressure (sitting) defined as diastolic blood pressure (DBP) \> 95 or less than (\<) 50 millimeters of mercury (mmHg) and/or systolic blood pressure (SBP) \> 150 or \< 90 mmHg confirmed by at least 1 repeat measurement * Have evidence of regular use of known drugs of abuse or show positive findings for such use on urinary drug screening * Will donate blood or participate in another clinical trial within 3 months or 5 half-lives of study drug (whichever is longer) of receiving the last study drug administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | From baseline up to 8 weeks post dose | Drug-related TEAEs are any untoward medical occurrence that either occurs or worsens at any time after treatment baseline, and in the opinion of the investigators is possibly related to study drug. A summary of SAEs and other nonserious AEs, regardless of whether or not they were possibly related to study drug, is located in the Reported Adverse Event section. |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα) | Predose up to 8 weeks post dose |
| Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin | Predose up to 8 weeks post dose |
| Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3016859 | Predose up to 8 weeks post dose |
| Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of LY3016859 From Time Zero to Infinity (AUC0-inf) | Predose up to 8 weeks post dose |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo IV Placebo administered once intravenously (IV). | 12 |
| Placebo SC Placebo administered once subcutaneously (SC). | 2 |
| 0.1 mg LY3016859 IV 0.1 milligram (mg) LY3016859 administered once intravenously. | 6 |
| 1 mg LY3016859 IV 1 mg LY3016859 administered once intravenously. | 6 |
| 10 mg LY3016859 IV 10 mg LY3016859 administered once intravenously. | 6 |
| 50 mg LY3016859 IV 50 mg LY3016859 administered once intravenously. | 6 |
| 250 mg LY3016859 IV 250 mg LY3016859 administered once intravenously. | 6 |
| 750 mg LY3016859 IV 750 mg LY3016859 administered once intravenously. | 6 |
| 50 mg LY3016859 SC 50 mg LY3016859 administered once subcutaneously. | 6 |
| Total | 56 |
Baseline characteristics
| Characteristic | Total | Placebo IV | Placebo SC | 0.1 mg LY3016859 IV | 1 mg LY3016859 IV | 10 mg LY3016859 IV | 50 mg LY3016859 IV | 250 mg LY3016859 IV | 750 mg LY3016859 IV | 50 mg LY3016859 SC |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 35.3 years STANDARD_DEVIATION 13.02 | 29.8 years STANDARD_DEVIATION 9.19 | 27.0 years STANDARD_DEVIATION 11.31 | 29.7 years STANDARD_DEVIATION 8.48 | 36.5 years STANDARD_DEVIATION 9.71 | 30.2 years STANDARD_DEVIATION 8.59 | 43.2 years STANDARD_DEVIATION 17.42 | 41.3 years STANDARD_DEVIATION 17.25 | 47.0 years STANDARD_DEVIATION 14.68 | 33.0 years STANDARD_DEVIATION 11.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants | 12 Participants | 2 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 6 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 3 Participants | 1 Participants | 5 Participants | 4 Participants | 2 Participants | 3 Participants | 5 Participants | 3 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 56 participants | 12 participants | 2 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 51 Participants | 11 Participants | 2 Participants | 6 Participants | 5 Participants | 6 Participants | 4 Participants | 5 Participants | 6 Participants | 6 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 |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 12 | 1 / 2 | 4 / 6 | 3 / 6 | 2 / 6 | 2 / 6 | 4 / 6 | 3 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE)
Drug-related TEAEs are any untoward medical occurrence that either occurs or worsens at any time after treatment baseline, and in the opinion of the investigators is possibly related to study drug. A summary of SAEs and other nonserious AEs, regardless of whether or not they were possibly related to study drug, is located in the Reported Adverse Event section.
Time frame: From baseline up to 8 weeks post dose
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | TEAE | 2 participants |
| Placebo IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | SAE | 0 participants |
| Placebo SC | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | TEAE | 0 participants |
| Placebo SC | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | SAE | 0 participants |
| 0.1 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | TEAE | 2 participants |
| 0.1 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | SAE | 0 participants |
| 1 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | TEAE | 3 participants |
| 1 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | SAE | 0 participants |
| 10 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | TEAE | 0 participants |
| 10 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | SAE | 0 participants |
| 50 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | SAE | 0 participants |
| 50 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | TEAE | 0 participants |
| 250 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | SAE | 0 participants |
| 250 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | TEAE | 0 participants |
| 750 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | TEAE | 1 participants |
| 750 mg LY3016859 IV | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | SAE | 0 participants |
| 50 mg LY3016859 SC | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | TEAE | 0 participants |
| 50 mg LY3016859 SC | Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE) | SAE | 0 participants |
Secondary
Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin
Time frame: Predose up to 8 weeks post dose
Population: All randomized participants who received at least one dose of study drug and had serum epiregulin measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin | 349927 hour*picograms/milliliter (h*pg/mL) | Standard Deviation 118584 |
| Placebo SC | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin | 331408 hour*picograms/milliliter (h*pg/mL) | Standard Deviation 52233.4 |
| 0.1 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin | 280500 hour*picograms/milliliter (h*pg/mL) | Standard Deviation 65395.6 |
| 1 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin | 296022 hour*picograms/milliliter (h*pg/mL) | Standard Deviation 94056.4 |
| 10 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin | 405745 hour*picograms/milliliter (h*pg/mL) | Standard Deviation 76219.5 |
| 50 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin | 379401 hour*picograms/milliliter (h*pg/mL) | Standard Deviation 59460.6 |
| 250 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin | 697442 hour*picograms/milliliter (h*pg/mL) | Standard Deviation 229112.6 |
| 750 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin | 2254733 hour*picograms/milliliter (h*pg/mL) | Standard Deviation 1035876 |
| 50 mg LY3016859 SC | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin | 474081 hour*picograms/milliliter (h*pg/mL) | Standard Deviation 280526 |
Secondary
Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα)
Time frame: Predose up to 8 weeks post dose
Population: All randomized participants who received at least one dose of study drug and had TGFα measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα) | 41271 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 109300.8 |
| Placebo SC | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα) | 8573 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 5072.1 |
| 0.1 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα) | 2515 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 2340 |
| 1 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα) | 4444 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 4234.6 |
| 10 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα) | 9718 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 9089.5 |
| 50 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα) | 4286 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 2578.9 |
| 250 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα) | 8244 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 6487.5 |
| 750 mg LY3016859 IV | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα) | 12075 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 17137 |
| 50 mg LY3016859 SC | Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα) | 10305 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 7555.2 |
Secondary
Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of LY3016859 From Time Zero to Infinity (AUC0-inf)
Time frame: Predose up to 8 weeks post dose
Population: All randomized participants who received at least one dose of study drug and had sufficient LY3016859 pharmacokinetic data to calculate AUC0-inf.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of LY3016859 From Time Zero to Infinity (AUC0-inf) | 9967 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 2375.4 |
| 0.1 mg LY3016859 IV | Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of LY3016859 From Time Zero to Infinity (AUC0-inf) | 235759 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 46760.1 |
| 1 mg LY3016859 IV | Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of LY3016859 From Time Zero to Infinity (AUC0-inf) | 2769626 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 516303.9 |
| 10 mg LY3016859 IV | Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of LY3016859 From Time Zero to Infinity (AUC0-inf) | 23180633 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 9009921.3 |
| 50 mg LY3016859 IV | Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of LY3016859 From Time Zero to Infinity (AUC0-inf) | 81450520 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 20101546.7 |
| 250 mg LY3016859 IV | Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of LY3016859 From Time Zero to Infinity (AUC0-inf) | 1054034 hour*nanograms/milliliter (h*ng/mL) | Standard Deviation 536160.4 |
Secondary
Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3016859
Time frame: Predose up to 8 weeks post dose
Population: All randomized participants who received at least one dose of study drug and had sufficient LY3016859 pharmacokinetic data to estimate Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3016859 | 36 nanograms/milliliter (ng/mL) | Standard Deviation 4.3 |
| Placebo SC | Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3016859 | 399 nanograms/milliliter (ng/mL) | Standard Deviation 95.6 |
| 0.1 mg LY3016859 IV | Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3016859 | 3812 nanograms/milliliter (ng/mL) | Standard Deviation 718.3 |
| 1 mg LY3016859 IV | Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3016859 | 18467 nanograms/milliliter (ng/mL) | Standard Deviation 1882.2 |
| 10 mg LY3016859 IV | Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3016859 | 106967 nanograms/milliliter (ng/mL) | Standard Deviation 20038 |
| 50 mg LY3016859 IV | Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3016859 | 271167 nanograms/milliliter (ng/mL) | Standard Deviation 59650.4 |
| 250 mg LY3016859 IV | Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3016859 | 3748 nanograms/milliliter (ng/mL) | Standard Deviation 1550.8 |