Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-KW-6356

Subjects will be screened to assess their eligibility to enter the study within approximately 4 weeks prior to dose administration. Subjects will be confined to the Clinical Research Unit (CRU) for their entire participation in this study. Eight subjects will be enrolled to allow 6 subjects to complete the study. Each subject will report to the CRU and be confined from Day -1 (the day before dosing) through at least Day 8 (168 hours postdose). A single dose of study drug will be administered on Day 1 (0 hour). On Day 8, subjects can be asked to remain as a resident within the CRU for an additional period to allow for ongoing 24-hour urine, fecal, and blood sample collections. These collections can continue up to a maximum of 336 hours postdose (Day 15). Subjects can be discharged prior to Day 15 if the following individual subject discharge criteria have been satisfied: ≥ 90% of the 14C dose recovered in combined urine and feces, and ≤ 1% of the total radioactive dose is recovered in combined excreta (urine and feces) in 3 consecutive 24-hour periods in which a fecal sample is provided.

Inclusion criteria

• Males, of any race, between 18 and 65 years of age, inclusive.
• Body mass index between 18.0 and 30.0 kg/m2, inclusive.
• In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations.
• Able to sign an ICF and willing to abide by the study restrictions.
• Will agree to use contraception.
• History of at least 1 bowel movement per day.

Exclusion criteria

• Any clinically significant illness as determined by the Principal Investigator.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance.
• Have received any investigational drug within 30 days or 5.5 half-lives, whichever is longer, prior to study dosing.
• History of drug or alcohol abuse or dependence within 2 years prior to signing of ICF.
• Hospital admission, surgery, within 3 months before investigational product administration.
• Positive hepatitis B surface antigen or hepatitis C RNA, or positive for acquired human immunodeficiency virus.
• Positive urine drug screen for drugs of abuse.
• History of requiring treatment for urinary retention within 3 months before investigational product administration.
• History of seizures.
• Subjects with history of, or active suicidal ideation, or suicide attempt.
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed). Subjects with cholecystectomy will not be allowed.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including inducers/inhibitors of CYP3A4 and St. John's wort, within 30 days prior to Day 1.
• Use or intend to use any prescription medications/products within 30 days or 5.5 half-lives (if known), whichever is longer, prior to Check-in.
• Use or intend to use slow-release medications/products considered to still be active within 30 days or 5.5 half-lives (if known), whichever is longer, prior to Check-in.
• Use of any nonprescription medications (for 14 days prior to Check-in).
• Use of tobacco- or nicotine-containing products within 3 months prior to Check-in, or positive cotinine.
• Receipt of blood products within 2 months prior to Check-in.
• Donation of blood (> 200 mL) from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
• Poor peripheral venous access.
• Have previously completed or withdrawn from this study or any other study investigating KW-6356, and have previously received the investigational product.
• Subjects with exposure to significant diagnostic or therapeutic radiation (eg, serial X-ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to Check-in.
• Subjects who have participated in a radiolabeled drug study where exposures are known to the Investigator within the previous 4 months prior to admission to the clinic for this study or participated in a radiolabeled drug study where exposures are not known to the Investigator within the previous 6 months prior to admission to the clinic for this study.
• Subjects who, in the opinion of the Investigator, should not participate in this study.