A Study to Determine the Effects of Itraconazole on the Pharmacokinetics (PK) of DS-8500 in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
Study will assess the effects of itraconazole on the pharmacokinetic (PK) parameters of single-dose DS-8500a in healthy subjects. This is an open-label study in healthy subjects.

Official Title
-----------------
An Open-Label, One-Sequence, Two-Period Study to Evaluate the Effects of Itraconazole on the Pharmacokinetics of DS-8500a in Healthy Subjects

Conditions
-----------------
Pharmacokinetics

Intervention / Treatment
-----------------
* Drug: DS-8500a
* Drug: Itraconazole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female subjects between 18 and 45 y of age, with a Body-Mass Index (BMI) of 18 kg/m2 to 30 kg/m2, inclusive, at Screening. Good health as determined by evaluations performed at Screening and during Enrollment on Day -1. Negative serum pregnancy test at Screening and a negative urine pregnancy test during Enrollment on Day -1 for all female subjects. Additionally, female subjects must be: Surgically sterile (ie, bilateral tubal ligation or removal of both ovaries and/or uterus at least 6 mo prior to dosing) Naturally postmenopausal (spontaneous cessation of menses) for at least 24 consecutive mo prior to dosing, with a follicle stimulating hormone (FSH) level at Screening of ≥ 40 mIU/mL Non-lactating Male subjects must agree to contraception (condom with spermicide) in addition to having their female partner (if of childbearing potential) use another form of contraception (eg, an intrauterine device, diaphragm with spermicide, oral contraceptive, injectables, or subdermal hormonal implant) from the first dose until 12 wk following last administration. Also, male subjects must not donate sperm during the study and afterwards for a period of 12 wk. Provided written informed consent prior to participating in the study. Able to understand and willing to comply with all the study requirements, and willing to allow the collection of all blood and urine specimens. Negative urine test for drugs of abuse (opiates, benzodiazepines, amphetamines, cannabinoids, cocaine, barbiturates, phencyclidine), cotinine, and alcohol at Screening and During Enrollment on Day -1. Willingness to abstain from grapefruit/grapefruit juice and Seville oranges 10 d before the first dose of study drug on Day 1 until the end of the study on Day 31. Willingness to refrain from consuming food or beverages containing caffeine/xanthine and alcohol 24 h prior to Enrollment on Day -1 until the end of the study on Day 31. Exclusion Criteria: History or current evidence of clinically significant cardiac, hepatic, renal, pulmonary, endocrine/metabolic, neurologic, infectious, gastrointestinal (ie, any condition which may affect drug absorption), hematologic, or oncologic disease. Laboratory results (serum chemistry, hematology, and urinalysis) outside of the normal range and considered clinically significant in the opinion of the PI. Liver function (AST, ALT, bilirubin) test results must be below the ULN at Screening and during Enrollment on Day -1. A QTcF interval duration > 450 msec at Screening. Participation in a previous DS-8500a study, or dosing with itraconazole, within 6 mo prior to the first dose. Known sensitivity to product components of DS-8500a and/or itraconazole. Current participation in another investigational study or prior participation in an investigational study within the past 30 d prior to the first dose. Use of any prescription or over-the-counter (OTC) medications (systemic or topical), vitamins, or dietary/herbal supplements, including St John's Wort (hypericin), within 14 d prior to the first dose. Consumption of more than 28 units of alcohol per wk (males) or 14 units of alcohol per wk (females), where 1 unit of alcohol equals 1/2 pint of beer, 4 ounces of wine, or 1 ounce of spirits, or significant history of alcoholism or drug/chemical abuse within the last 2 y. Use of tobacco products or nicotine-containing products, including smoking cessation aids, such as gums or patches, within 6 mo prior to the first dose. Positive test result for HBsAg, HCV, or HIV antibody. Employment by the clinic. Familial relationship (spouse and/or first degree relative) with another study participant. Any other reason that, in the opinion of the PI, precludes subject participation in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single study arm<br>DS-8500a and itraconazole | Drug: DS-8500a<br>* DS-8500a 25mg tablet<br>Drug: Itraconazole<br>* 200mg itraconazole<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum concentration (Cmax) of DS-8500a | To assess the effects of itraconazole on the pharmacokinetic (PK) parameters of single-dose DS-8500a | Day 1 to Day 6 | 
| time of maximum concentration (Tmax) of DS-8500a | To assess the effects of itraconazole on the pharmacokinetic (PK) parameters of single-dose DS-8500a | Day 1 to Day 6 | 
| Area under the concentration curve (AUC) of DS-8500a | To assess the effects of itraconazole on the pharmacokinetic (PK) parameters of single-dose DS-8500a | Day 1 to Day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of adverse events | To assess the the safety of DS-8500a | Day 1 to Day 31 | 
| change in physical examination findings | To assess the the safety of DS-8500a | Day 1 to Day 31 | 
| change in 12-lead electrocardiogram | To assess the the safety of DS-8500a | Day 1 to Day 31 | 
| change in vital sign measurements | To assess the the safety of DS-8500a | Day 1 to Day 31 | 
| change in clinical laboratory test results | To assess the the safety of DS-8500a | Day 1 to Day 31 |