Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-KW-6356
Study Details
Study Description
Brief Summary
This is an open-label, single-dose study in healthy male subjects to investigate the absorption, metabolism, and excretion (AME) of KW-6356.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: KW-6356 Single oral dose of carbon-14-KW-6356. |
Drug: KW-6356
Single oral dose of KW-6356
|
Outcome Measures
Primary Outcome Measures
- Cmax [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Maximum observed concentration (KW-6356 in plasma and total radioactivity in plasma and blood).
- tmax [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Time of maximum observed concentration (KW-6356 in plasma and total radioactivity in plasma and blood).
- AUC0-t [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
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).
- %AUCextra [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Percentage of estimated part for the calculation of AUC0-∞ (KW-6356 in plasma and total radioactivity in plasma and blood).
- t1/2 [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Elimination half-life (KW-6356 in plasma and total radioactivity in plasma and blood).
- kel [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Elimination rate constant (KW-6356 in plasma and total radioactivity in plasma and blood).
- Vz/F [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Apparent volume of distribution during terminal phase (KW-6356 in plasma).
- CL/F [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Apparent oral clearance (KW-6356 in plasma).
- MRT [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Mean residence time (KW-6356 in plasma).
- 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.]
- Aeurine [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Cumulative amount excreted in urine (total radioactivity in urine).
- feurine [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Fraction of the dose administered excreted in urine (total radioactivity in urine).
- Aefeces [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Cumulative amount excreted in feces (total radioactivity in feces).
- fefeces [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Fraction of the dose administered excreted in feces (total radioactivity in feces).
- Aetotal [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Total amount excreted (total radioactivity in urine and feces).
- fetotal [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Fraction of the dose administered excreted in urine and feces (total radioactivity in urine and feces).
- Metabolic profiling and identification (plasma, urine, and feces). [Pre-dose up to 168 hours post dose, up to 336 hours post dose.]
Secondary Outcome Measures
- Adverse Events [From screening through study completion, an average of 6 weeks.]
Number of subjects experiencing an adverse event related to treatment.
- Severe adverse events. [From screening through study completion, an average of 6 weeks.]
Number of subjects experiencing a severe adverse event related to treatment.
- Serum chemistry, hematology, and urinalysis. [From screening through study completion, an average of 6 weeks.]
Number of subjects with abnormal laboratory values that are related to treatment.
- Vital signs [From screening through study completion, an average of 6 weeks.]
Number of subjects with abnormal vital signs that are related to treatment.
- 12-lead ECG. [From screening through study completion, an average of 6 weeks.]
Number of subjects with abnormal ECG that are related to treatment.
- Physical examination. [From screening through study completion, an average of 6 weeks.]
Number of subjects with abnormal physical exam findings that are related to treatment.
Eligibility Criteria
Criteria
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.
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In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations.
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Able to sign an ICF and willing to abide by the study restrictions.
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Will agree to use contraception.
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History of at least 1 bowel movement per day.
Exclusion Criteria:
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Any clinically significant illness as determined by the Principal Investigator.
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History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance.
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Have received any investigational drug within 30 days or 5.5 half-lives, whichever is longer, prior to study dosing.
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History of drug or alcohol abuse or dependence within 2 years prior to signing of ICF.
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Hospital admission, surgery, within 3 months before investigational product administration.
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Positive hepatitis B surface antigen or hepatitis C RNA, or positive for acquired human immunodeficiency virus.
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Positive urine drug screen for drugs of abuse.
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History of requiring treatment for urinary retention within 3 months before investigational product administration.
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History of seizures.
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Subjects with history of, or active suicidal ideation, or suicide attempt.
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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.
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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.
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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.
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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.
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Use of any nonprescription medications (for 14 days prior to Check-in).
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Use of tobacco- or nicotine-containing products within 3 months prior to Check-in, or positive cotinine.
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Receipt of blood products within 2 months prior to Check-in.
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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.
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Poor peripheral venous access.
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Have previously completed or withdrawn from this study or any other study investigating KW-6356, and have previously received the investigational product.
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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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Covance Clinical Research Unit Inc. | Madison | Wisconsin | United States | 53704 |
Sponsors and Collaborators
- Kyowa Kirin, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 6356-009