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

Healthy Male Subjects Clinical Trial

Official title:

A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-KW-6356 Following a Single Oral Dose in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04147910
• Other study ID #: 6356-009
• Status: Completed
• Phase: Phase 1
• Start date: August 21, 2019
• Est. completion date: October 2, 2019

Study information

• Verified date: April 2024
• Source: Kyowa Kirin Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, single-dose study in healthy male subjects to investigate the absorption, metabolism, and excretion (AME) of KW-6356.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: October 2, 2019
• Est. primary completion date: October 2, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Males, of any race, between 18 and 65 years of age, inclusive.

2. Body mass index between 18.0 and 30.0 kg/m2, inclusive.

3. In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations.

4. Able to sign an ICF and willing to abide by the study restrictions.

5. Will agree to use contraception.

6. History of at least 1 bowel movement per day.

Exclusion Criteria:

1. Any clinically significant illness as determined by the Principal Investigator.

2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance.

3. Have received any investigational drug within 30 days or 5.5 half-lives, whichever is longer, prior to study dosing.

4. History of drug or alcohol abuse or dependence within 2 years prior to signing of ICF.

5. Hospital admission, surgery, within 3 months before investigational product administration.

6. Positive hepatitis B surface antigen or hepatitis C RNA, or positive for acquired human immunodeficiency virus.

7. Positive urine drug screen for drugs of abuse.

8. History of requiring treatment for urinary retention within 3 months before investigational product administration.

9. History of seizures.

10. Subjects with history of, or active suicidal ideation, or suicide attempt.

11. 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.

12. 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.

13. 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.

14. 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.

15. Use of any nonprescription medications (for 14 days prior to Check-in).

16. Use of tobacco- or nicotine-containing products within 3 months prior to Check-in, or positive cotinine.

17. Receipt of blood products within 2 months prior to Check-in.

18. 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.

19. Poor peripheral venous access.

20. Have previously completed or withdrawn from this study or any other study investigating KW-6356, and have previously received the investigational product.

21. 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.

22. 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.

23. Subjects who, in the opinion of the Investigator, should not participate in this study.

Related Conditions & MeSH terms

• Healthy Male Subjects

Intervention

Drug:
• KW-6356
Single oral dose of KW-6356

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit Inc.	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Kyowa Kirin, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax	Maximum observed concentration (KW-6356 in plasma and total radioactivity in plasma and blood).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	tmax	Time of maximum observed concentration (KW-6356 in plasma and total radioactivity in plasma and blood).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	AUC0-t	Area under the drug concentration-time curve from time zero to the last quantifiable concentration (KW-6356 in plasma and total radioactivity in plasma and blood).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	%AUCextra	Percentage of estimated part for the calculation of AUC0-8 (KW-6356 in plasma and total radioactivity in plasma and blood).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	t1/2	Elimination half-life (KW-6356 in plasma and total radioactivity in plasma and blood).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	kel	Elimination rate constant (KW-6356 in plasma and total radioactivity in plasma and blood).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	Vz/F	Apparent volume of distribution during terminal phase (KW-6356 in plasma).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	CL/F	Apparent oral clearance (KW-6356 in plasma).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	MRT	Mean residence time (KW-6356 in plasma).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	Whole blood/plasma concentration ratio (total radioactivity in blood and plasma).		Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	Aeurine	Cumulative amount excreted in urine (total radioactivity in urine).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	feurine	Fraction of the dose administered excreted in urine (total radioactivity in urine).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	Aefeces	Cumulative amount excreted in feces (total radioactivity in feces).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	fefeces	Fraction of the dose administered excreted in feces (total radioactivity in feces).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	Aetotal	Total amount excreted (total radioactivity in urine and feces).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	fetotal	Fraction of the dose administered excreted in urine and feces (total radioactivity in urine and feces).	Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Primary	Metabolic profiling and identification (plasma, urine, and feces).		Pre-dose up to 168 hours post dose, up to 336 hours post dose.
Secondary	Adverse Events	Number of subjects experiencing an adverse event related to treatment.	From screening through study completion, an average of 6 weeks.
Secondary	Severe adverse events.	Number of subjects experiencing a severe adverse event related to treatment.	From screening through study completion, an average of 6 weeks.
Secondary	Serum chemistry, hematology, and urinalysis.	Number of subjects with abnormal laboratory values that are related to treatment.	From screening through study completion, an average of 6 weeks.
Secondary	Vital signs	Number of subjects with abnormal vital signs that are related to treatment.	From screening through study completion, an average of 6 weeks.
Secondary	12-lead ECG.	Number of subjects with abnormal ECG that are related to treatment.	From screening through study completion, an average of 6 weeks.
Secondary	Physical examination.	Number of subjects with abnormal physical exam findings that are related to treatment.	From screening through study completion, an average of 6 weeks.