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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers Bioavailability Study
• Intervention / Treatment: Drug: selumetinib 75mg single dose; Other: [14C] selumetinib IV solution

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Bioavailability	To calculate absolute bioavailability we used the formula: Area Under the Curve (oral dose)/Area Under the Curve (intravenous dose)*100	0 to 72 hours post-dose

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Stuart Mair, Quotient Clinical LTD

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: August 8, 2014
• First Submitted That Met QC Criteria: September 10, 2014
• First Posted (Estimate): September 12, 2014

Study Record Updates

• Last Update Posted (Estimate): April 5, 2016
• Last Update Submitted That Met QC Criteria: March 4, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: cancer; pharmacokinetics; bioavailability; AZD6244; I phase
• Other Study ID Numbers: D1532C00080