Trial record 6 of 92 for:    MEK Inhibitor AZD-6244

To Assess the Effect of Rifampicin on the Pharmacokinetics of Selumetinib in Healthy Male Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02046850
First received: January 24, 2014
Last updated: April 28, 2014
Last verified: April 2014
  Purpose
Study to assess the effect of Rifampicin on the pharmacokinetics of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Male Volunteers

Condition Intervention Phase
Solid Tumours
Drug: selumetinib
Drug: rifampicin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase I Open-label, Single-center Study to Assess the Effect of the CYP3A4 Inducer Rifampicin on the Pharmacokinetics of a 75 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Volunteers Aged 18 to 45 Years

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Pharmacokinetics of selumetinib by assessment of area under the plasma concentration-time curve from time zero to infinity (AUC) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments


Secondary Outcome Measures:
  • Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of area under the plasma concentration-time from time zero to the time of the last quantifiable concentration (AUC(0-t) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments

  • Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of area under the plasma concentration-time curve from time zero to 12 hours post-dose AUC(0-12) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments

  • Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of maximum plasma concentration (Cmax) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments

  • Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of time to Cmax (tmax) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments

  • Pharmacokinetics of selumetinib, by assessment of apparent systemic plasma clearance (CL/F) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments

  • Pharmacokinetics of selumetinib, by assessment of apparent volume at distribution equilibrium, mean residence time (MRT)*CL/F (Vss/F) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments

  • Pharmacokinetics of selumetinib, by assessment of apparent volume at distribution (Vz/F) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments

  • Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of terminal half-life (t1/2) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments

  • Pharmacokinetics of selumetinib, N-desmethyl selumetinib,(and the amide metabolite, if deemed appropriate) by assessment of terminal rate constant (λz) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments

  • Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of AUC metabolite to parent ratio, n-desmethyl selumetinib (MRAUC) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments

  • Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of Cmax metabolite to parent ratio, n-desmethyl selumetinib (MRCmax) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments

  • Pharmacokinetics of selumetinib by assessment of mean residence time (MRT) [ Time Frame: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post dose ] [ Designated as safety issue: No ]
    Samples taken during each of the 3 treatments


Other Outcome Measures:
  • Safety variables (adverse events, physical examinations, ophthalmologic assessments, vital signs, clinical laboratory assessments, and 12 lead electrocardiograms) [ Time Frame: Baseline (Day-1) up to Day 25 ] [ Designated as safety issue: Yes ]
    Assessments performed during each of the 3 treatments


Estimated Enrollment: 24
Study Start Date: February 2014
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: selumetinib 75mg.
Volunteers will receive selumetinib 75mg administered by mouth, as a capsule
Drug: selumetinib
Volunteers will receive a single oral dose of 75 mg selumetinib on day 1 (Treatment A).
Other Name: AZD6244
rifampicin 600mg.
Volunteers will receive rifampicin 600mg administered by mouth, as a capsule
Drug: rifampicin
Volunteers will receive single, daily, oral doses of 600 mg rifampicin on Days 4 to 11 (Treatment B).
Other Name: AZD6244
Experimental: selumetinib 75mg and rifampicin 600mg
Volunteers will receive selumetinib 75mg and rifampicin 600mg, by mouth, as a capsule
Drug: selumetinib
On day 12 volunteers will receive a single oral dose of 75 mg selumetinib (Treatment C).
Drug: rifampicin
On day 12 volunteers will receive a single oral dose of 600 mg rifampicin. Once daily rifampicin administrations will continue through to Day 14 (Treatment C).

Detailed Description:
A Open-label, Single-center Study to Assess the Effect of the CYP3A4 inducer Rifampicin on the Pharmacokinetics of a 75 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Volunteers
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria: 1. Have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive). 2. Must not have smoked or used nicotine products within the previous 3 months. 3. Have a calculated creatinine clearance (CrCL) greater than 50 mL/min using the Cockcroft-Gault formula.

Exclusion Criteria: 1. Subjects of Japanese or non-Japanese Asian ethnicity. 2. Any one parent or grandparent (maternal or paternal) is Japanese or non-Japanese Asian (eg, China, Taiwan, Korea, Philippines, Thailand, Vietnam and Malaysia). Asian Indians are acceptable. 3. Current or past history of central serous retinopathy or retinal vein thrombosis,intra-ocular pressure greater than 21 mmHg or uncontrolled glaucoma. 4. Any clinically relevant abnormal findings in physical examination, hematology, clinical chemistry, urinalysis, vital signs or ECG at baseline in the opinion of the investigator. 5. History of presence of any clinically significant disease or disorder in the opinion of the investigator.

  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: NCT02046850

Locations
United States, Kansas
Research Site
Overland Park, Kansas, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Eleanor Lisbon, MD Quintiles 6700 W 115th Street, Kansas, US
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02046850     History of Changes
Other Study ID Numbers: D1532C00085 
Study First Received: January 24, 2014
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Phase I, healthy, pharmacokinetics,

Additional relevant MeSH terms:
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Rifampin
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers

ClinicalTrials.gov processed this record on August 25, 2016