- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT02878096
Bioavailability of [14C]-SK-1404 ADME & IV Microtracer Study
An Open-Label, 2-Part Sequential Dose Study Designed to Assess the Absolute Bioavailability, Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-SK-1404 Administered to Healthy Male Subjects
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
Tutkimuksen yleiskatsaus
Yksityiskohtainen kuvaus
This is a single-centre, 2-part, open-label, non-randomised, sequential, single dose study in healthy male subjects. It is planned to enrol a single cohort of 6 healthy male subjects who will participate in Parts 1 and Part 2 of the study.
In Part 1, each subject will receive a single PO dose of SK-1404 followed by an IV microtracer dose of [14C]-SK-1404.
In Part 2, each subject will receive a single PO dose of [14C]-SK-1404.
Opintotyyppi
Ilmoittautuminen (Todellinen)
Vaihe
- Vaihe 1
Yhteystiedot ja paikat
Opiskelupaikat
-
-
Nottingham
-
Ruddington, Nottingham, Yhdistynyt kuningaskunta, NG11 6JS
- Quotient Clinical
-
-
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Perustiede
- Jako: Ei käytössä
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: [14C]-SK-1404
|
In Part 1, each subject will receive a single PO dose of SK-1404 followed by an IV microtracer dose of [14C]-SK-1404.
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Absolute bioavailability (F) calculated with the AUC values of IV administration in Part 1 and PO administration in Part 2
Aikaikkuna: Predose to 96hr
|
Predose to 96hr
|
|
|
Mass balance recovery of total radioactivity in urine, faeces and all excreta
Aikaikkuna: Predose to 168hr
|
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
Aikaikkuna: Predose to 168hr
|
Predose to 168hr
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Ae total radioactivity in plasma by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
Aikaikkuna: Predose to 168hr
|
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
Aikaikkuna: Predose to 168hr
|
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
Aikaikkuna: Predose to 168hr
|
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
Aikaikkuna: Predose to 168hr
|
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
Aikaikkuna: Predose to 168hr
|
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
Aikaikkuna: Predose to 168hr
|
Predose to 168hr
|
|
|
Number and structural identification of unknown metabolites of SK-1404 with an AUC of more than 10% of circulating total radioactivity
Aikaikkuna: Predose to 168hr
|
Predose to 168hr
|
|
|
The peak plasma concentration (Cmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The time from dosing at which Cmax was apparent (Tmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The elapsed time from dosing at which the analyte was first quantifiable in a concentration vs time profile (Tlag) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The area under the concentration-time curve from dosing to the last measurable concentration (AUC(0-last)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The area under the concentration-time curve from dosing extrapolated to infinity (AUC(0-inf)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The percentage of AUC(0-inf) extrapolated beyond the last measured time point (AUC%extrap) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The terminal elimination rate constant calculated from the slope of the apparent elimination phase (lambda-z) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The apparent terminal elimination half-life (T1/2) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The apparent total clearance (CL/F) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The apparent volume of distribution (Vd) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The apparent volume of distribution (Vss) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The mean residence time (MRT) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Aikaikkuna: Predose to 96hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 96hr
|
|
The peak plasma concentration (Cmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The time from dosing at which Cmax was apparent (Tmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The elapsed time from dosing at which the analyte was first quantifiable in a concentration vs time profile (Tlag) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The area under the concentration-time curve from dosing to the last measurable concentration (AUC(0-last)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The area under the concentration-time curve from dosing extrapolated to infinity (AUC(0-inf)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The percentage of AUC(0-inf) extrapolated beyond the last measured time point (AUC%extrap) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The terminal elimination rate constant calculated from the slope of the apparent elimination phase (lambda-z) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The apparent terminal elimination half-life (T1/2) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The absolute bioavailability (F, PO vs IV from Part 1) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The apparent total clearance (CL/F) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The apparent volume of distribution (Vd/F) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
The mean residence time (MRT) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Aikaikkuna: Predose to 168hr
|
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
|
Predose to 168hr
|
|
To collect further information about the safety and tolerability of IMP
Aikaikkuna: Predose to 168hr
|
By assessing physical examination, safety laboratory tests, vital signs, electrocardiograms (ECGs) and AEs.
|
Predose to 168hr
|
Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Päätutkija: Litza McKenzie, MBChB BScMedSci, Quotient Clinical
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Arvio)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Arvio)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- QCL117764
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
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