A Relative Bioavailability and Food Effect Study of New Formulations

Lilly

Status and phase: Completed; Phase 1

Conditions: Chronic Inflammatory Disorder; Arthritis, Rheumatoid

Treatments: Drug: LY3009104

Study type: Interventional

Funder types: Industry

Identifiers

NCT01398475

14016 (Other Identifier)

I4V-MC-JADH (Other Identifier)

Details and patient eligibility

About

The purpose of this trial is to assess the effect of 3 formulations on the relative bioavailability of LY3009104. Participants will receive single dose of LY3009104 on 4 separate occasions with and without food. Safety evaluation and serial pharmacokinetic (PK) samples will be collected during each treatment period. Approximately 5 to 7 days of washout period between each treatment and a follow-up visit will occur approximately 5 to 7 days after the last dose of study drug.

Enrollment: 15 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Overtly healthy males or females as determined by medical history and physical examination
• Have a body mass index (BMI) of 18.5 to 29.9 kilograms per square meter (kg/m^2), inclusive, at screening
• Have 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
• Have normal blood pressure and pulse rate as determined by the investigator
• Have venous access sufficient to allow for blood sampling
• 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

Male Participants:

• Agree to use two forms of highly effective methods of birth control [oral, injectable, or implanted hormonal contraceptives; condom with spermicidal foam/gel/film/cream/suppository; occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; intrauterine device; intrauterine system, for example, progestin releasing coil; and vasectomised male (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate)] with female partners of childbearing potential during the study and for at least 3 months following the last dose of study drug

Female participants:

• Are women of non-childbearing potential, defined as: women with Mayer Rokitansky Kuster Hauser Syndrome (also referred to as Clinical Absence of Uterus and Vagina), or women who have had surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation), or women greater than 60 years of age, or women greater than 40 and less than 60 years of age who have had a cessation of menses for at least 12 months and a follicle-stimulating hormone (FSH) test confirming non-childbearing potential [FSH ≥40 milli-international units per milliliter (mIU/mL)]

Exclusion criteria

• Are currently enrolled in, or have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have a history of adverse drug reactions or "drug allergy" to more than 3 types of systemically administered medications (all penicillins and cephalosporins may be considered 1 type of medication for this purpose)
• Are participants who have previously received the investigational product in this study, have completed or withdrawn from this study or any other study investigating LY3009104
• 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
• Current or recent history (<30 days prior to screening and/or <45 days prior to Check-in) of a clinically significant bacterial, fungal, parasitic, viral (not including rhinopharyngitis), or mycobacterial infection
• Have an absolute neutrophil count (ANC) less than 2000 cells per microliter (cell/μL). For abnormal values, a single repeat will be allowed
• Have a history of, or current, cardiovascular, respiratory, hepatic, renal, gastrointestinal, 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
• Regularly use known drugs of abuse
• Have had symptomatic herpes zoster or herpes simplex infection within 90 days prior to the first dose
• Have been exposed to a live vaccine within 12 weeks prior to the first dose or expected to need/receive a live vaccine (including herpes zoster vaccination) during the course of the study
• Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
• Show evidence of hepatitis C and/or positive hepatitis C antibody
• Show evidence of hepatitis B and/or positive hepatitis B surface antigen
• Intend to use over-the-counter or prescription medication and herbal supplements within 14 days prior to dosing and during the study
• Intend to use vitamins and mineral supplements within 2 days prior to dosing and during the study
• Have donated blood of more than 450 milliliters (mL) within the previous 3 months
• Have consumed grapefruit, starfruit, pomelos, or products containing these fruits, 7 days prior to the first dose and during the study
• 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 48 hours prior to admission in each period until the 48 hour PK sample has been collected [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 used any tobacco-containing or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to enrollment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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15 participants in 4 patient groups

LY3009104 Reference Formulation

Experimental group

Description:

8 milligrams (mg) LY3009104 (two 4-mg phosphate salt capsules), administered orally in the fasted state, once only. There will be a washout period of 5 to 7 days between doses of study drug.

Treatment:

Drug: LY3009104

LY3009104 Test Formulation 1

Experimental group

Description:

8 mg LY3009104 (one 8-mg smaller particle free base tablet), administered orally in the fasted state, once only. There will be a washout period of 5 to 7 days between doses of study drug.

Treatment:

Drug: LY3009104

LY3009104 Test Formulation 2

Experimental group

Description:

8 mg LY3009104 (one 8-mg larger particle free base tablet), administered orally in the fasted state, once only. There will be a washout period of 5 to 7 days between doses of study drug.

Treatment:

Drug: LY3009104

LY3009104 Test Formulation 2 + Meal

Experimental group

Description:

8 mg LY3009104 (one 8-mg larger particle free base tablet), administered orally with high-fat/high calorie meal, once only. There will be a washout period of 5 to 7 days between doses of study drug.

Treatment:

Drug: LY3009104