Phase 1 Study to Evaluate ASN002 Absorption, Metabolism, and Excretion of [14C] Following a Single Oral Dose in Healthy Male Subjects

Study Overview
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Brief Summary
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Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C] ASN002 Following a Single Oral Dose in Healthy Male Subjects

Detailed Description
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This will be a Phase 1, open-label, nonrandomized, single-dose study in healthy male subjects. Subjects will be admitted into the Clinical Research Unit (CRU) on Day 1 and be confined to the CRU until at least Day 7. On Day 1, subjects will receive a single oral dose of [14C] ASN002 at 60 mg containing approximately 300 μCi [14C] ASN002. Subjects will be discharged on Day 7 if the following discharge criteria are met: plasma radioactivity levels below the limit of quantitation for 2 consecutive collections, and ≥90% mass balance recovery, or ≤1% of the total radioactive dose is recovered in combined excreta (urine and feces) in 3 consecutive 24 hour periods. If discharge criteria are not met by Day 7, subjects will remain in the CRU up to a maximum of Day 10.

Official Title
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A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C] ASN002 Following a Single Oral Dose in Healthy Male Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: [14C] ASN002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males, of any race, between 20 and 60 years of age, inclusive, at Screening. Body mass index between 18.5 and 30.0 kg/m2, inclusive, at Screening. In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is not acceptable) at Screening or Check in as assessed by the Investigator (or designee). Males will agree to use contraception as defined in the Protocol body Able to comprehend and willing to sign an ICF and to abide by the study restrictions. History of a minimum of 1 bowel movement per day. Exclusion Criteria: Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee). History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee). 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 not be allowed). History of alcoholism or drug/chemical abuse within 2 years prior to Check in. Consumption of alcohol from 72 hours prior to Check-in until Discharge. Consumption of foods and beverages containing poppy seeds, grapefruit, or Seville oranges from 7 days prior to Check-in until Discharge. Consumption of caffeine containing foods and beverages from 48 hours before Check-in until Discharge. Positive urine drug screen (including cotinine) at Screening or positive alcohol breath test or positive urine drug screen (including cotinine) at Check in. Positive hepatitis panel and/or positive human immunodeficiency virus test. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives (if known), whichever is longer, prior to Check-in. Use or intend to use any medications/products known to alter drug absorption, metabolism, or excretion processes, including St. John's wort, within 14 days prior to Check in, unless deemed acceptable by the Investigator (or designee). Use or intend to use any prescription medications/products within 14 days prior to Check in, unless deemed acceptable by the Investigator (or designee). Use or intend to use slow release medications/products considered to still be active within 14 days prior to Check in, unless deemed acceptable by the Investigator (or designee). Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant derived preparations within 7 days prior to Check in, unless deemed acceptable by the Investigator (or designee). Use of tobacco or nicotine containing products within 3 months prior to Check in. Receipt of blood products within 2 months prior to Check in. Donation of blood from 56 days 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 ASN002, and have previously received the investigational medicinal product (IMP). 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. The total 12-month exposure from this study and a maximum of 2 other previous radiolabeled studies within 4 to 12 months prior to this study will be within the CFR recommended levels considered safe, per United States Title 21 CFR 361.1: less than 5,000 mrem whole body annual exposure with consideration given to the half-lives of the previous radiolabeled study drugs received. Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [14C] ASN002<br>[14C] ASN002 | Drug: [14C] ASN002<br>* [14C] ASN002<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - maximum observed plasma concentration (plasma and whole blood) |  | at pre-dose and up to 144 hours post-dose. If collection is extended up to Day 10: at up to 216 hours post-dose. | 
| tmax - time at which Cmax occurs (plasma and whole blood) |  | at pre-dose and up to 144 hours post-dose. If collection is extended up to Day 10: at up to 216 hours post-dose. | 
| AUC0 t - area under the plasma concentration time curve from time zero to the last measurable concentration (plasma and whole blood) |  | at pre-dose and up to 144 hours post-dose. If collection is extended up to Day 10: at up to 216 hours post-dose. | 
| AUC0-∞ - area under the plasma concentration-time curve from time zero to infinity (plasma and whole blood) |  | at pre-dose and up to 144 hours post-dose. If collection is extended up to Day 10: at up to 216 hours post-dose. | 
| t½ - apparent terminal elimination half-life (plasma and whole blood) |  | at pre-dose and up to 144 hours post-dose. If collection is extended up to Day 10: at up to 216 hours post-dose. | 
| CL/F - apparent total clearance (plasma and whole blood) |  | at pre-dose and up to 144 hours post-dose. If collection is extended up to Day 10: at up to 216 hours post-dose. | 
| VZ/F - apparent volume of distribution (plasma and whole blood) |  | at pre-dose and up to 144 hours post-dose. If collection is extended up to Day 10: at up to 216 hours post-dose. | 
| Total radioactivity in urine and feces | %Ae (urine), %Ae (feces) and %Ae (total): amount excreted and cumulative amount excreted in urine and feces | at pre-dose and up to 144 hours post-dose. If collection is extended up to Day 10: at up to 216 hours post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic Profiling/identification and determination of relative abundance of ASN002 and the metabolites of ASN002 in plasma, urine, and feces |  | Up to 10 days | 
| Safety and tolerability as measured by incidence and severity of adverse events (AEs) |  | Up to 10 days |