Bioavailability of [14C]-SK-1404 ADME & IV Microtracer Study

NCT02878096 | Completed Phase 1 DMC

• 1 other identifier: QCL117764
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of the study are:

• To determine the absolute bioavailability of SK-1404
• To assess the mass balance recovery after a single oral (PO) dose of carbon-14 (14C)-SK-1404
• To provide plasma, urine and faecal samples for metabolite profiling and structural identification The secondary objectives of the study are:
• To determine the routes and rates of elimination of \[14C\]-SK-1404
• To identify the chemical structure of each metabolite with an exposure (AUC) of more than 10% of circulating total radioactivity
• To explore the intravenous (IV) pharmacokinetics (PK) of \[14C\]-SK-1404
• To further explore the PO PK of SK-1404
• To provide additional safety and tolerability information for SK-1404

Conditions

Nocturia

Keywords

nocturnal polyuria

Outcome Measures

Primary Outcomes (3)

• Absolute bioavailability (F) calculated with the AUC values of IV administration in Part 1 and PO administration in Part 2

  Predose to 96hr

• Mass balance recovery of total radioactivity in urine, faeces and all excreta

  Amount excreted (Ae), and Ae as a percentage of the administered dose (%Ae), cumulative recovery (Cum Ae) and cumulative recovery expressed as a percentage of the dose (Cum %Ae)

  Predose to 168hr

• Number and structural identification of known and unknown metabolites of SK-1404 in the plasma, urine and faeces samples

  Predose to 168hr

Secondary Outcomes (32)

• Ae total radioactivity in plasma by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404

  Predose to 168hr

• %Ae total radioactivity in plasma by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404

  Predose to 168hr

• Cum Ae (total) for urine by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404

  Predose to 168hr

• Cum %Ae (total) for urine by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404

  Predose to 168hr

• Cum Ae (total) for faeces by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404

  Predose to 168hr

Study Arms (1)

[14C]-SK-1404

EXPERIMENTAL

Drug: [14C]-SK-1404

Interventions

[14C]-SK-1404 DRUG

In Part 1, each subject will receive a single PO dose of SK-1404 followed by an IV microtracer dose of \[14C\]-SK-1404.

[14C]-SK-1404

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males
• Age 30 to 65 years of age
• Body mass index of 18.0 to 35.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
• Must be willing and able to communicate and participate in the whole study
• Must provide written informed consent
• Must have regular bowel movements (ie average stool production of ≥1 and ≤3 stools per day)
• Must agree to use an adequate method of contraception

You may not qualify if:

• Males with pregnant partners
• Participation in a clinical research study within the 3 months prior to IMP dose
• Subjects who are study site employees, or immediate family members of a study site or sponsor employee
• Subjects who have previously been enrolled in this study
• Subjects who have previously been dosed with SK-1404
• History of any drug or alcohol abuse in the past 2 years
• Regular alcohol consumption in males \>21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) in the past year
• Current smokers and those who have smoked within the last 12 months; this includes cigarettes, e-cigarettes and nicotine replacement products. A breath carbon monoxide reading of greater than 10 ppm at screening or admission
• Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study
• Subjects who have been enrolled in an ADME study in the last 12 months
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
• Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1)
• Aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase \>1.5 × upper limit of normal confirmed by repeat testing
• Serum sodium below the lower limit of normal

Sponsors & Collaborators

• Sanwa Kagaku Kenkyusho Co., Ltd.: lead

Study Sites (1)

Quotient Clinical

Ruddington, Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Nocturia

Condition Hierarchy (Ancestors)

Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Litza McKenzie, MBChB BScMedSci

  Quotient Clinical

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2016
• First Posted: August 25, 2016
• Study Start: July 1, 2016
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: October 14, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)