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Trial record 6 of 91 for:    MEK Inhibitor AZD-6244

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02322749
First received: December 9, 2014
Last updated: July 20, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Healthy Volunteers Bioequivalence or Bioavailability Study
Drug: selumetinib 75mg single dose
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase I, Single Centre, Randomised, Open Label, Crossover Study to Assess the Bioequivalence or Relative Bioavailability of Variants of Selumetinib (AZD6244, Hyd-Sulfate) Blue Capsules in Healthy Male Volunteers Aged 18 to 45 Years

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Bioequivalence of the Free Base Variant of Selumetinib (Treatment B) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib Cmax] [ Time Frame: 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). ] [ Designated as safety issue: No ]
    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.

  • Bioequivalence of the Free Base Variant of Selumetinib (Treatment B) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC] [ Time Frame: 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). ] [ Designated as safety issue: No ]
    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.

  • Bioequivalence of the Free Base Variant of Selumetinib (Treatment B) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC(0-t)] [ Time Frame: 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). ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Relative Bioavailability of the TPGS Capsule Variant (Treatment C) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib Cmax] [ Time Frame: 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). ] [ Designated as safety issue: No ]
    The relative bioavailability of the TPGS capsule variant of selumetinib (Treatment C) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the Cmax of selumetinib in healthy volunteers.

  • Relative Bioavailability of the TPGS Capsule Variant (Treatment C) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC] [ Time Frame: 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). ] [ Designated as safety issue: No ]
    The relative bioavailability of the TPGS capsules variant of selumetinib (Treatment C) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the AUC of selumetinib in healthy volunteers.

  • Relative Bioavailability of the TPGS Capsule Variant (Treatment C) Compared to the Blue Reference Capsule (Treatment A) [Selumetinib AUC(0-t)] [ Time Frame: 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). ] [ Designated as safety issue: No ]
    The relative bioavailability of the TPGS capsule variant of selumetinib (Treatment C) as compared to the blue reference capsule (Treatment A) was evaluated by comparing the AUC[0-t] of selumetinib in healthy volunteers.

  • The PK of the Metabolite N-desmethyl Selumetinib by Assessment of Cmax [ Time Frame: 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). ] [ Designated as safety issue: No ]
    The PK of the metabolite N-desmethyl selumetinib was evaluated by assessing the Cmax of the metabolite in healthy volunteers after oral administration of single doses of the blue reference capsule (Treatment A), the free base variant capsule (Treatment B) and the TPGS variant capsule (Treatment C).

  • The PK of N-desmethyl Selumetinib by Assessment of the AUC(0-t) [ Time Frame: 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). ] [ Designated as safety issue: No ]
    The PK of the metabolite N-desmethyl selumetinib was evaluated by assessing the AUC(0-t) of the metabolite in healthy volunteers after oral administration of single doses of the blue reference capsule (Treatment A), the free base variant capsule (Treatment B) and the TPGS variant capsule (Treatment C).


Enrollment: 48
Study Start Date: February 2015
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A
AZD6244 blue reference capsules (3 x 25 mg) administered orally
Drug: selumetinib 75mg single dose
3 blue capsules of 25 mg given as a single dose
Other Name: Selumetinib
Experimental: Treatment B
AZD6244 blue capsules (3 x 25 mg) Variant 1 (free base variant) administered orally
Drug: selumetinib 75mg single dose
3 capsules of 25 mg given as a single dose
Other Name: Selumetinib
Experimental: Treatment C
AZD6244 blue capsules (3 x 25 mg) Variant 2 (vitamin E polyethylene glycol succinate [TPGS] variant) administered orally
Drug: selumetinib 75mg single dose
3 capsules of 25 mg given as a single dose
Other Name: Selumetinib

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
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 45 years 3.Calculated creatinine clearance (CrCL) >50 mL/minute using the Cockcroft-Gault formula 4.Healthy volunteers with sexual partners who could become pregnant should agree to use 2 highly effective methods of contraception. Healthy volunteers with sexual partners who are pregnant should agree to use an effective method of contraception (barrier method) from the first administration until 12 weeks after the last administration of the investigational product. Healthy volunteers should avoid sperm donation during the study and for 12 weeks after the last administration of the investigational product 5.Use no nicotine containing products for at least 3 months prior to screening 6.For inclusion in the genetic component of the study, healthy volunteers provide written informed consent for genetic research.

Exclusion Criteria:

1.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

  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: NCT02322749

Locations
United Kingdom
Research Site
London, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Olufeyikemi Oluwayi, MBChB Quintiles, Inc.
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02322749     History of Changes
Other Study ID Numbers: D1532C00078 
Study First Received: December 9, 2014
Results First Received: April 28, 2016
Last Updated: July 20, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
bioequivalence
bioavailability
pharmacokinetics
Phase I
AZD6244
cancer

ClinicalTrials.gov processed this record on September 28, 2016