- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico 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
Visão geral do estudo
Descrição detalhada
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.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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Nottingham
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Ruddington, Nottingham, Reino Unido, NG11 6JS
- Quotient Clinical
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Ciência básica
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: [14C]-SK-1404
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In Part 1, each subject will receive a single PO dose of SK-1404 followed by an IV microtracer dose of [14C]-SK-1404.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Absolute bioavailability (F) calculated with the AUC values of IV administration in Part 1 and PO administration in Part 2
Prazo: Predose to 96hr
|
Predose to 96hr
|
|
|
Mass balance recovery of total radioactivity in urine, faeces and all excreta
Prazo: 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
Prazo: Predose to 168hr
|
Predose to 168hr
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Ae total radioactivity in plasma by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: Predose to 168hr
|
By assessing physical examination, safety laboratory tests, vital signs, electrocardiograms (ECGs) and AEs.
|
Predose to 168hr
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Litza McKenzie, MBChB BScMedSci, Quotient Clinical
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- QCL117764
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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