Trial record 6 of 77 for:    MEK Inhibitor AZD-6244

A Study to Assess the Absolute Bioavailability of Oral Selumetinib in Healthy Male Volunteers.

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02238782
First received: August 8, 2014
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

To assess the absolute bioavailability of oral selumetinib in healthy male volunteers


Condition Intervention Phase
Healthy Volunteers Bioavailability Study
Drug: selumetinib 75mg single dose
Other: [14C] selumetinib IV solution
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
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

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Absolute bioavailability of selumetinib in healthy male volunteers [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
    Absolute bioavailability will be calculated as: (selumetinib AUC/[14C] selumetinib AUC) x ([14C] selumetinib dose/selumetinib dose) x 100


Secondary Outcome Measures:
  • Safety and tolerability of selumetinib [ Time Frame: in maximum 32 days from screening visit ] [ Designated as safety issue: Yes ]
    Adverse events, physical examination, vital signs, clinical laboratory assessment, 12-lead ECG, echocardiogram, ophthalmic examination.

  • PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Maximum observed plasma concentration (Cmax) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • 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)) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Time to maximum observed concentration (tmax) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Terminal half life (t1/2) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Terminal rate constant (λz) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • PK (Pharmacokinetics) of selumetinib and N-desmethyl selumetinib after single oral dose of selumetinib in terms of Mean residence time (MRT) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • PK (Pharmacokinetics) of selumetinib after single oral dose in terms of Apparent systemic plasma clearance (CL/F) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • PK (Pharmacokinetics) of selumetinib after single oral dose of selumetinib in terms of Apparent volume of distribution at steady state (Vss/F) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • PK (Pharmacokinetics) of selumetinib after single oral dose of selumetinib in terms of Apparent volume of distribution during the terminal phase (Vz/F) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of Cmax [ Time Frame: From single dose administrationat Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of AUC [ Time Frame: From single dose administrationat Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of AUC(0-t) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of AUC(0-12) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of tmax [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of t1/2 [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of λz [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of MRT [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of Systemic clearance (CL) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of Volume of distribution at steady state (Vss) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters after radiolabeled intravenous IV (14C) microdose of selumetinb in terms of Volume of distribution during the terminal phase (Vz) [ Time Frame: From single dose administration at Day 1 up to 72 hours post dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: October 2014
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: selumetinib 75mg single dose
3 capsules of 25 mg administered orally
Drug: selumetinib 75mg single dose
3 capsules of 25 mg given as a single dose
Other Name: Selumetinib
Other: [14C] selumetinib IV solution
single, radiolabeled, IV (infused), microdose (80 μg) of [14C] selumetinib, infused using a syringe pump as a 15-minute infusion, administered 1h 15 min after receiving the oral dose
Other Name: [14C] selumetinib IV solution

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02238782

Contacts
Contact: Quotient Clinical study information +44 (0) 115 974 9000 ClinicalTrialTransparency@astrazeneca.com
Contact: Ian Nisbet +44 (0) 115 931 5503 Ian.Nisbet@quotientclinical.com

Locations
United Kingdom
Research Site Recruiting
Ruddington, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Stuart Mair Quotient Clinical Ltd
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02238782     History of Changes
Other Study ID Numbers: D1532C00080
Study First Received: August 8, 2014
Last Updated: October 15, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
bioavailability
pharmacokinetics
I phase
AZD6244
cancer

Additional relevant MeSH terms:
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014