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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02046850
Recruitment Status : Completed
First Posted : January 28, 2014
Last Update Posted : April 29, 2014
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
Study to assess the effect of Rifampicin on the pharmacokinetics of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Male Volunteers

Condition or disease Intervention/treatment Phase
Solid Tumours Drug: selumetinib Drug: rifampicin Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : February 2014
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Rifampin

Arm Intervention/treatment
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).




Primary Outcome Measures :
  1. 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 ]
    Samples taken during each of the 3 treatments


Secondary Outcome Measures :
  1. 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 ]
    Samples taken during each of the 3 treatments

  2. 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 ]
    Samples taken during each of the 3 treatments

  3. 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 ]
    Samples taken during each of the 3 treatments

  4. 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 ]
    Samples taken during each of the 3 treatments

  5. 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 ]
    Samples taken during each of the 3 treatments

  6. 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 ]
    Samples taken during each of the 3 treatments

  7. 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 ]
    Samples taken during each of the 3 treatments

  8. 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 ]
    Samples taken during each of the 3 treatments

  9. 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 ]
    Samples taken during each of the 3 treatments

  10. 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 ]
    Samples taken during each of the 3 treatments

  11. 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 ]
    Samples taken during each of the 3 treatments

  12. 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 ]
    Samples taken during each of the 3 treatments


Other Outcome Measures:
  1. 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 ]
    Assessments performed during each of the 3 treatments



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02046850


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

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02046850    
Other Study ID Numbers: D1532C00085
First Posted: January 28, 2014    Key Record Dates
Last Update Posted: April 29, 2014
Last Verified: April 2014
Keywords provided by AstraZeneca:
Phase I, healthy, pharmacokinetics,
Additional relevant MeSH terms:
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Rifampin
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
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