A Study to Assess the Relative Bioavailability of Process Variants of Selumetinib in Healthy Male Volunteers

NCT02322749 | Completed Phase 1 Results

• 1 other identifier: D1532C00078
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

A Study to assess, against a reference selumetinib capsule, if the drug levels of a variant of selumetinib capsule are comparable, and to assess how drug levels differed in another variant of Selumetinib in Healthy Male Volunteers.

Conditions

Healthy Volunteers Bioequivalence or Bioavailability Study

Keywords

bioequivalence; bioavailability; pharmacokinetics; Phase I; AZD6244; cancer

Outcome Measures

Primary Outcomes (3)

• Bioequivalence of the Free Base Variant of Selumetinib (Treatment B) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib Cmax]

  The bioequivalence of the free base variant of selumetinib (Treatment B) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the maximum observed plasma concentration (Cmax) of selumetinib in healthy volunteers.

  Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post dose for each of the separate treatment periods (Visits 2, 3 and 4).

• Bioequivalence of the Free Base Variant of Selumetinib (Treatment B) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC]

  The bioequivalence of the free base variant of selumetinib (Treatment B) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC) of selumetinib in healthy volunteers.

  Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post dose for each of the separate treatment periods (Visits 2, 3 and 4).

• Bioequivalence of the Free Base Variant of Selumetinib (Treatment B) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC(0-t)]

  The bioequivalence of the free base variant of selumetinib (Treatment B) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the AUC from time zero to the time of the last quantifiable concentration (AUC\[0-t\]) of selumetinib in healthy volunteers.

  Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post dose for each of the separate treatment periods (Visits 2, 3 and 4).

Secondary Outcomes (5)

• Relative Bioavailability of the TPGS Capsule Variant (Treatment C) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib Cmax]

  Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).

• Relative Bioavailability of the TPGS Capsule Variant (Treatment C) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC]

  Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).

• Relative Bioavailability of the TPGS Capsule Variant (Treatment C) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC(0-t)]

  Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).

• The PK of the Metabolite N-desmethyl Selumetinib by Assessment of Cmax

  Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).

• The PK of N-desmethyl Selumetinib by Assessment of the AUC(0-t)

  Blood samples were collected pre-dose, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).

Study Arms (3)

Treatment A

EXPERIMENTAL

AZD6244 blue reference capsules (3 x 25 mg) administered orally

Drug: selumetinib 75mg single dose

Treatment B

EXPERIMENTAL

AZD6244 blue capsules (3 x 25 mg) Variant 1 (free base variant) administered orally

Drug: selumetinib 75mg single dose

Treatment C

EXPERIMENTAL

AZD6244 blue capsules (3 x 25 mg) Variant 2 (vitamin E polyethylene glycol succinate \[TPGS\] variant) administered orally

Drug: selumetinib 75mg single dose

Interventions

selumetinib 75mg single dose DRUG

3 blue capsules of 25 mg given as a single dose

Also known as: Selumetinib

Treatment A

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Healthy male volunteers of Japanese or non Japanese Asian, or Indian ethnicity 2.Any one parent or grandparent (maternal or paternal) is Japanese or non-Japanese Asian or Indian 3.Involvement in the planning and/or conduct of the study. 4.Previous randomisation to treatment in the present study 5.Participation in another clinical study within 3 month before Visit 1, or participation in a method development study 1 month before Visit 1. 6.Current or past history of central serous retinopathy or retinal vein thrombosis, intraocular pressure greater than 21 mmHg or uncontrolled glaucoma 7.Any clinically significant disease or disorder that may put the healthy volunteer at risk because of participation in the study, influence the result of the study or influence the healthy volunteer's ability to participate in the study 8.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 healthy volunteer at risk because of his participation in the study. 9.Use of prescribed medications and over-the-counter drugs (including herbal remedies) known to have moderate or strong cytochrome P450 (CYP) 3A4 or CYP2C19 inducer or inhibitory effects from 30 days prior to the first administration of investigational product until the follow up visit 10.Use of any other prescribed medications and over-the-counter drugs (including herbal remedies, vitamins and minerals) within 2 weeks or 5 times the half life, whichever is longer, of the respective drug prior to Visit 2, with the exception of occasional use of acetaminophen (paracetamol or TYLENOL®) and over-the-counter adrenergic nasal spray for relief of nasal congestion. No medications known to prolong the QT/corrected QT interval (QTc) interval are allowed 11.Excessive intake of caffeine containing drinks or food. 12.Any intake of grapefruit and Seville oranges or other products containing grapefruit or Seville oranges within 7 days of the first admission 13.A definite or suspected personal history of intolerance or hypersensitivity to drugs and/or their excipients 14.Plasma donation or any blood donation/blood loss greater than 500 mL during the 3 months prior to screening 15.History of, or current alcohol or drug abuse. 16.A suspected/manifested infection according to the International Air Transport Association (IATA) Categories A and B infectious substances 17.Healthy male volunteers who do not agree to use at least 2 effective methods of contraception 18.Positive results at screening for human immunodeficiency virus (HIV) and/or hepatitis B and/or hepatitis C 19.Planned inpatient surgery, dental procedure or hospitalisation during the study 20.Healthy male volunteers who, in the opinion of the Principal Investigator, should not participate in the study 21.Healthy male volunteers with a LVEF \<55% 22.Previous bone marrow transplant 23.Whole blood transfusion within 120 days of the genetic sample collection

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

London, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Interventions

AZD 6244

Results Point of Contact

• Title: Information Centre
• Organization: AstraZeneca

Information.centre@astrazeneca.com

Study Officials

• Olufeyikemi Oluwayi, MBChB

  Quintiles, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2014
• First Posted: December 23, 2014
• Study Start: February 1, 2015
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: August 31, 2016
• Results First Posted: August 31, 2016

Record last verified: 2016-07

Locations

GB (1)