Clinical trial NCT01449630: A Study of LY3031207 in Healthy Subjects
Official title: A Single-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of LY3031207 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-10-10
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This is a phase I study of LY3031207 in healthy subjects. The purposes of this study are to look at safety, how well the study drug is tolerated, and how much of the study drug gets into the blood stream and how long it takes the body to get rid of it when given to humans. Information about any side effects that may occur will also be collected. Subjects will participate in the study for approximately 3 months. This study is for research purposes only and is not intended to treat any medical condition.


Eligibility criteria: Inclusion Criteria:

* Male subjects agree to use a reliable method of birth control during the study and for 3 months following the last dose of the investigational product
* Women 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 menopause
* Menopausal women include women with either spontaneous amenorrhea for at least 12 months, not induced by a medical condition such as anorexia nervosa and not taking medications during the amenorrhea that induced the amenorrhea (for example \[e.g.\], oral contraceptives, hormones, gonadotropin-releasing hormone, antiestrogens, selective estrogen receptor modulators, or chemotherapy) or spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating hormone level greater than 40 milli-International Unit (mIU/mL)
* Overtly healthy based on the history and physical examinations as determined by the investigator
* Between body mass index (BMI) of 18.5 and 32.0 kilogram per meter squared (kg/m\^2), inclusive
* Normotensive defined as supine systolic blood pressure (BP) \<140 of millimeter mercury (mmHg), and diastolic BP \<90 mmHg, without the use of any antihypertensives, or results that are judged to be not clinically significant by the Investigator. Blood pressure may be retested up to 2 additional times, under well rested conditions
* Clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator
* Ex vivo whole blood prostaglandin E(PGE) synthesis after lipopolysaccharide (LPS) stimulation of no less than 5 nanograms/milliliter (ng/mL).
* Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
* Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site

Exclusion Criteria:

* Are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product or unapproved use of a drug with a short half-life, or within 5 half-life of an investigational product with a half-life longer than 5 days, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
* Have known allergies to LY3031207 or any components of the formulation, celecoxib or sulfonamides. Subjects with known aspirin allergy or allergic reaction to non-steroidal anti-inflammatory drugs (NSAIDs) should also be excluded
* Are persons who have previously completed or withdrawn from this study or any other study investigating LY3031207 and who have previously received the investigational product
* Have an abnormality in the 12-lead Electrocardiogram (ECG), including QTc interval with Bazett's correction \>450 millisecond (msec) for men and \>470 msec for women or an abnormality that, in the opinion of the investigator, increases the risks associated with participating in the study. Electrocardiogram may be repeated after 5 minutes resting quietly, if the subject's heart rate is \>75 beats per minute
* History of, within the last 2 years, or presence of active cardiovascular disease, including acute myocardial infarction, unstable angina, congestive heart failure, stroke, or transient ischemic attack
* Presence of clinically significant active bleeding or history of bleeding diathesis at the time of screening
* Presence of active peptic ulcer disease, Gastrointestinal (GI) bleeding, chronic gastritis, inflammatory bowel disease, chronic diarrhea, or positive H. pylori serology
* Evidence of hepatitis C and/or positive hepatitis C antibody
* Evidence of hepatitis B and/or positive hepatitis B surface antigen
* Evidence of other chronic liver disease, including chronic alcoholic disease; non-alcoholic steatohepatitis; recent (within 3 months of screening) history of acute viral hepatitis; or subjects with known Gilbert Syndrome
* History of active neuropsychiatric disease
* Evidence of human immunodeficiency virus (HIV) infection and/or positive HIV antibodies
* Have a significant history of or current other cardiovascular, respiratory (especially asthma and chronic obstructive pulmonary disease), hepatic, renal, GI, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data. History of prior surgeries (at least 3 months prior to dosing), such as splenectomy, cholecystectomy, and appendectomy are not exclusionary
* Regularly use of known drugs of abuse and/or show positive findings on urinary drug screening
* Are women with a positive pregnancy test or women who are lactating
* Intended use of over-the-counter medications or prescription medication within 14 days prior to dosing, this includes but is not limited to antihypertensives, diuretics, antiplatelet or anticoagulant drugs, and antidepressants
* Any use of NSAIDs, celecoxib, aspirin or acetaminophen (at doses \>1 gram \[gm\] per day) within 14 days of screening
* Any use of herbal or dietary supplements, or grapefruit and/or grapefruit juice, Seville oranges, starfruit, or pomegranate within 14 days prior to dosing of study drug
* Have donated blood of more than 500 milliliter (mL) within the last month
* Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) or are unwilling to stop alcohol consumption for the duration of the study (1 unit = 12 ounce \[oz\] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
* Subjects who smoke more than 10 cigarettes per day or are unwilling to follow the Clinical Research Unit (CRU) smoking rules
* Subjects with any major surgery within 30 days prior to screening or subjects with planned surgeries to occur during the study

Primary outcomes:
measure: Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE
timeFrame: Baseline, up to 4 months
Secondary outcomes:
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3031207
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 96, 144 hours post dose
measure: Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 96, 144 hours post dose
measure: Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation
timeFrame: Predose, 0.5, 1, 2, 8, 24 and 144 hours post dose.
measure: Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM)
timeFrame: 0 to 2, 2 to 4, 4 to 6, 6 to 12 and 12 to 24 hours post dose
measure: Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM)
timeFrame: 0 to 2, 2 to 4, 4 to 6, and 6 to 12 hours post dose
measure: Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM)
timeFrame: 0 to 2, 2 to 4, 4 to 6, and 6 to 12 hours post dose
Other outcomes:
Locations:
city: Evansville
country: United States
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.
state: Indiana
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: