A Study of LY3031207 in Healthy Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01449630
First received: October 5, 2011
Last updated: April 13, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Healthy Volunteers
Drug: LY3031207
Drug: Placebo
Drug: Celecoxib
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: A Single-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of LY3031207 in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Number of Participants with one or more drug related Adverse Events (AEs) or any Serious AEs [ Time Frame: Baseline to study completion (estimate 4 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: Area under the concentration-time curve (AUC) of LY3031207 [ Time Frame: Pre-dose up to 144 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum concentration (Cmax) of LY3031207 [ Time Frame: Pre-dose up to 144 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacodynamics: Percent change from baseline of ex vivo whole blood prostaglandin E (PGE) synthesis after lipopolysaccharide (LPS) stimulation [ Time Frame: Pre-dose up to 144 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacodynamics: Percent change from baseline of urinary excretion of Prostaglandin E(2) Metabolite (PGEM) metabolites [ Time Frame: Predose up to 24 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacodynamics: Percent change from baseline of urinary excretion of Prostacyclin Metabolite (PGIM) [ Time Frame: Pre dose up to 12 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacodynamics: Percent change from baseline of urinary excretion of Thromboxane A Metabolite (TXAM) [ Time Frame: Pre dose up to 12 hours post dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: October 2011
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY3031207
Single dose of up to 900mg of LY3031207 administered orally in up to three occasions separated by at least a 3 week wash-out period between each dose.
Drug: LY3031207
Administered orally
Placebo Comparator: Placebo
Single dose of placebo administered orally in up to two occasions separated by at least a 3 week wash-out period between each dose.
Drug: Placebo
Administered orally
Active Comparator: Celecoxib
Single 400mg dose of celecoxib administered orally on one occasion.
Drug: Celecoxib
Administered orally

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 (eg., 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 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 kg/m^2, inclusive
  • Normotensive defined as supine systolic blood pressure (BP) <140 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 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 nonsteroidal 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 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 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 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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01449630

Locations
United States, Indiana
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.
Evansville, Indiana, United States, 47710
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01449630     History of Changes
Other Study ID Numbers: 14283, I5W-EW-LBCA
Study First Received: October 5, 2011
Last Updated: April 13, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Central Nervous System Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 20, 2014