Clinical trial NCT01545583: A Study of LY3016859 in Healthy Volunteers
Official title: Study of the Safety, Tolerability and Pharmacokinetics of LY3016859 After Single Intravenous and Subcutaneous Dosing in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-03-07
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With One or More Drug-Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAE)
timeFrame: From baseline up to 8 weeks post dose
Secondary outcomes:
measure: Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Transforming Growth Factor Alpha (TGFα)
timeFrame: Predose up to 8 weeks post dose
measure: Pharmacodynamics: Area Under the Concentration-Time Curve (AUC) of Serum Epiregulin
timeFrame: Predose up to 8 weeks post dose
measure: Pharmacokinetics: Maximum Serum Concentration (Cmax) of LY3016859
timeFrame: Predose up to 8 weeks post dose
measure: Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of LY3016859 From Time Zero to Infinity (AUC0-inf)
timeFrame: Predose up to 8 weeks post dose
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern Time (UTC/GMT- 5 hours, EST)
role: STUDY_DIRECTOR
References: