Healthy Volunteers Bioavailability Study Clinical Trial
Official title:
A Study to Assess the Absolute Bioavailability of a Single Oral Dose of Selumetinib With Respect to an Intravenous Microdose of [14C] Selumetinib in Healthy Male Volunteers
To assess the absolute bioavailability of oral selumetinib in healthy male volunteers
| Status | Completed |
| Enrollment | 21 |
| Est. completion date | October 2014 |
| Est. primary completion date | October 2014 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Male |
| Age group | 18 Years to 65 Years |
| Eligibility |
Inclusion Criteria: 1. Provision of written informed consent 2. Healthy male volunteers aged 18 to 65 3. Male volunteers with sexual partners who are pregnant or who could become pregnant should use two highly effective methods of contraception (including one barrier method) for at least 14 days after completing the study and should avoid sperm donation for 14 days after study completion. 4. Body mass index between 18 and 30 kg/m2 and weighing between 50 and 100 kg. 5. Use no nicotine containing products for at least 3 months prior to screening with a negative cotinine screen at screening and Day 1 (Visit 2) 6. Calculated creatinine clearance greater than 50 mL/min using Cockcroft Gault formula. Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study 2. Previous enrolment for treatment in the present study 3. Japanese or non Japanese Asian or Indian ethnicity. 4. Any one parent or grandparent is Japanese or non-Japanese Asian or Indian. 5. Treatment with another new chemical entity or participation in any other clinical study that included drug treatment within at least 3 months 6. Participation in another clinical study involving administration of [14C] radioactivity within 1 year. 7. Current or past history of central serious retinopathy or retinal vein thrombosis, intraocular pressure greater than 21 mmHg or uncontrolled glaucoma. 8. Any clinically significant disease or disorder which, may put the volunteer at risk because of participation in the study, influence the study result or influence the volunteer's ability to participate in the study. 9. Any clinically relevant abnormal findings in physical examination, haematology, clinical chemistry, urinalysis, vital signs or 12 lead ECG at Visit 1, which may put the volunteer at risk because of his participation in the study. 10. Use of drugs with enzyme inducing properties such as St John's Wort within 4 weeks prior to the administration of the investigational product 11. Use of any other prescribed medicine and over the counter drugs within 2 week or 5 times the half life, whichever is longer prior to the administration of the investigational product up to and including the follow up visit (Visit 4), with the exception of occasional use of paracetamol or ibuprofen and over the counter adrenergic nasal spray. No medications known to prolong the QT/corrected QT interval are allowed. 12. Excessive intake of caffeine containing drinks or food 13. Any intake of grapefruit and Seville oranges including products containing grapefruit or Seville oranges within 7 days of the admission on Day -1. 14. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to Selumetinib. 15. Plasma donation within 1 month of screening (Visit 1) or any blood donation or blood loss greater than 500 mL during the 3 months prior to screening (Visit 1). 16. History of or current alcohol or drug abuse. 17. A suspected or manifested infection according to the International Air Transport Association Categories A and B infectious substances. 18. Positive results on screening tests for HIV and/or hepatitis B and/or hepatitis C. 19. Baseline LVEF <55% measured by echocardiography. 20. Planned inpatient surgery, dental procedure or hospitalisation during the study. 21. Healthy male volunteers who in the opinion of the Principal Investigator, should not participate in the study. 22. Judgment by Principal Investigator that the volunteer should not participate in the study if they have ongoing or recent minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements. |
Allocation: Non-Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | Research Site | Ruddington |
| Lead Sponsor | Collaborator |
|---|---|
| AstraZeneca |
United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Absolute bioavailability of selumetinib in healthy male volunteers | Absolute bioavailability will be calculated as: (selumetinib AUC/[14C] selumetinib AUC) x ([14C] selumetinib dose/selumetinib dose) x 100 | From single dose administration at Day 1 up to 72 hours post dose | No |
| Secondary | Safety and tolerability of selumetinib | Adverse events, physical examination, vital signs, clinical laboratory assessment, 12-lead ECG, echocardiogram, ophthalmic examination. | in maximum 32 days from screening visit | Yes |
| Secondary | PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Maximum observed plasma concentration (Cmax) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Area under the plasma concentration-time curve from zero extrapolated to infinity (AUC) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration AUC(0-t) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Area under the plasma concentration-time curve from time zero to 12 hours postdose (AUC(0-12)) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Time to maximum observed concentration (tmax) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Terminal half life (t1/2) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Terminal rate constant (?z) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Mean residence time (MRT) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | PK (Pharmacokinetics) of selumetinib after single oral dose in terms of Apparent systemic plasma clearance (CL/F) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | PK (Pharmacokinetics) of selumetinib after single oral dose of selumetinib in terms of Apparent volume of distribution at steady state (Vss/F) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | PK (Pharmacokinetics) of selumetinib after single oral dose of selumetinib in terms of Apparent volume of distribution during the terminal phase (Vz/F) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | PK (Pharmacokinetics) of N-desmethyl selumetinib after single oral dose of selumetinib in terms of the metabolite to parent AUC and Cmax ratios (MR AUC and MR Cmax) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of Cmax | From single dose administrationat Day 1 up to 72 hours post dose | No | |
| Secondary | Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of AUC | From single dose administrationat Day 1 up to 72 hours post dose | No | |
| Secondary | Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of AUC(0-t) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of AUC(0-12) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of tmax | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of t1/2 | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of ?z | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of MRT | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of Systemic clearance (CL) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of Volume of distribution at steady state (Vss) | From single dose administration at Day 1 up to 72 hours post dose | No | |
| Secondary | Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of Volume of distribution during the terminal phase (Vz) | From single dose administration at Day 1 up to 72 hours post dose | No |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
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