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Study Evaluating the Pharmacokinetic and Mass Balance of Single Dose [14C] AZD9291 in Volunteers

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ClinicalTrials.gov Identifier: NCT02096679
Recruitment Status : Completed
First Posted : March 26, 2014
Results First Posted : July 30, 2015
Last Update Posted : October 21, 2015
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
Study to evaluate the pharmacokinetic and Mass Balance of single dose [14C] AZD9291 in healthy male volunteers

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: AZD9291 Phase 1

Detailed Description:
A Single-centre, Non-Randomised, Open-label, Pharmacokinetic and Mass Balance Study of Orally Administered [14C]-AZD9291 in Healthy Male Volunteers

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase I, Single-centre, Non-Randomised, Open-label, Pharmacokinetic and Mass Balance Study of Orally Administered [14C]-AZD9291 in Healthy Male Volunteers
Study Start Date : May 2014
Actual Primary Completion Date : August 2014
Actual Study Completion Date : August 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: [14C]-AZD9291 20mg (oral solution)
Volunteers will receive 20 mg [14C]-AZD9291 containing a nominal 1 μCi activity, administered by mouth, as a solution.
Drug: AZD9291
Volunteer will receive a single oral dose of 20 mg [14C]-AZD9291 as a solution on Day 1




Primary Outcome Measures :
  1. Percentage of Radioactive Dose of [14C] Radiolabelled AZD9291 Recovered in Urine, Faeces, and in Total. [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. Urine (h): 0-4, 4-8, 8-12, 12-24, every 24 hrs to 504, 648-72, 816-40, 984-1008 and 1992-2016. Faeces: 0-24h and then as per urine. ]
    The percentage of radioactive dose of [14C] radiolabelled AZD9291 recovered in urine, faeces, and in total, up to Day 85.


Secondary Outcome Measures :
  1. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration AUC(0-t) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of area under the concentration-time curve from time zero to the time of the last quantifiable concentration AUC(0-t), derived from the curve taken during the treatment period.

  2. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve From Time Zero to the Time of 72 Hours AUC(0-72) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72 ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of area under the concentration-time curve from time zero to the time of 72 hours AUC(0-72), derived from the curve taken during the treatment period.

  3. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve From Time Zero to 24 Hours AUC(0-24) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of area under the concentration-time curve from time zero to the time of 24 hours AUC(0-24), derived from the curve taken during the treatment period.

  4. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Maximum Plasma Concentration (Cmax) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of maximum plasma concentration (Cmax), derived from the curve taken during the treatment period.

  5. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Time to Cmax (Tmax) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of by assessment of time to Cmax (tmax), derived from the curve taken during the treatment period.

  6. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Lag Time Before Observation of Quantifiable Analyte Concentrations (Tlag) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of lag time before observation of quantifiable analyte concentrations (tlag), derived from the curve taken during the treatment period.

  7. Pharmacokinetics of AZD9291 Plasma, Whole Blood and Plasma [14C] Radioactivity by Assessment of Apparent Oral Clearance (CL/F) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291 plasma, whole blood and plasma [14C] radioactivity by assessment of apparent oral clearance (CL/F), derived from the curve taken during the treatment period.

  8. Pharmacokinetics of AZD9291 Plasma, Whole Blood and Plasma [14C] Radioactivity by Assessment of Apparent Volume of Distribution (Vz/F) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of apparent volume of distribution (Vz/F), derived from the curve taken during the treatment period.

  9. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Half-life (t1/2,λz) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of elimination half-life (t1/2,λz), derived from the curve taken during the treatment period.

  10. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Rate Constant (λz) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of elimination rate constant (λz), derived from the curve taken during the treatment period.

  11. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of AUC Metabolite to Parent Ratio, AZ7550 or AZ5104 AUC/AZD9291 AUC Adjusted for Differences in Molecular Weight (M/PAUC) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of AUC metabolite to parent ratio, AZ7550 or AZ5104 AUC/AZD9291 AUC adjusted for differences in molecular weight (M/PAUC), derived from the curves taken during the treatment period.

  12. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Cmax Metabolite to Parent Ratio, AZ7550 or AZ5104 (M/PCmax) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of Cmax metabolite to parent ratio, AZ7550 or AZ5104 (M/PCmax), derived from the curves taken during the treatment period.

  13. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Cmax Ratio of Plasma AZD9291, AZ7550 or AZ5104 (PL) to Plasma Radioactivity (Cmax(PL)/Cmax(PR)) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of Cmax ratio of plasma AZD9291, AZ7550 or AZ5104 (PL) to plasma radioactivity (Cmax(PL)/Cmax(PR)), derived from the curves taken during the treatment period.

  14. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Cmax Ratio of Whole Blood Radioactivity (WBR) to PR Cmax (WBR)/Cmax(PR) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of Cmax ratio of whole blood radioactivity (WBR) to PR Cmax (WBR)/Cmax(PR), derived from the curves taken during the treatment period.

  15. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of AUC Ratio of Plasma AZD9291, AZD7550 or AZD5104 (PL) to Plasma Radioactivity (PR) AUC(PL)/AUC(PR) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of AUC ratio of plasma AZD9291, AZD7550 or AZD5104 (PL) to plasma radioactivity (PR) AUC(PL)/AUC(PR), derived from the curves taken during the treatment period.

  16. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of AUC Ratio of WBR to PR (AUC(WBR)/AUC(PR)) [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of AUC ratio of WBR to PR (AUC(WBR)/AUC(PR)), derived from the curves taken during the treatment period.

  17. Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve AUC [ Time Frame: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, every 24 to 168, 336, 504, 648, 816, 904 and 1992. ]
    Pharmacokinetics of AZD9291, its metabolites and whole blood and plasma [14C] radioactivity by assessment of area under the concentration-time curve AUC, derived from the curve taken during the treatment period.

  18. Pharmacokinetics of AZD9291, Its Metabolites and Urine [14C] Total Radioactivity by Assessment of Urine Concentration or Concentration Equivalent x Urine Volume (Aeu) [ Time Frame: Urine (h): 0-4, 4-8, 8-12, 12-24, every 24 hrs to 504, 648-72, 816-40, 984-1008 and 1992-2016. ]
    Pharmacokinetics of AZD9291, its metabolites and urine [14C] total radioactivity by assessment of urine concentration or concentration equivalent x urine volume (Aeu), derived from the curve taken during the treatment period.

  19. Pharmacokinetics of AZD9291 and Urine [14C] Total Radioactivity by Assessment of Percentage (or Fraction) of Actually Administered Dose / Radioactivity (Feu) [ Time Frame: Urine (h): 0-4, 4-8, 8-12, 12-24, every 24 hrs to 504, 648-72, 816-40, 984-1008 and 1992-2016. ]
    Pharmacokinetics of AZD9291 and urine [14C] total radioactivity by assessment of percentage (or fraction) of actually administered dose / radioactivity (feu), derived from the curve taken during the treatment period.



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.


Ages Eligible for Study:   30 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

1, Volunteers must be willing to use reliable methods of contraception (condom and spermicide), even if their partners are postmenopausal, surgically sterile, or using an effective hormonal method of contraception or intrauterine coil. 2. In addition, volunteers must agree to continue to take similar contraceptive precautions until 6 months after the last administration of AZD9291 and avoid procreative sex as well as sperm donation for 6 months.

Exclusion Criteria: 1, Any clinically relevant abnormalities in physical examination, vital signs, hematology,clinical chemistry, urinalysis or ECG at baseline in the opinion of the investigator. 2. Radiation exposure from clinical studies, including that from the present study, excluding background radiation but including diagnostic X-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. -


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): NCT02096679


Locations
United Kingdom
Research Site
Nottingham, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Joanne Collier, MD Quotient Clinical Ltd, Mere Way, Ruddington Fields, Nottingham, United Kingdom. NG11 6JS

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02096679     History of Changes
Other Study ID Numbers: D5160C00011
First Posted: March 26, 2014    Key Record Dates
Results First Posted: July 30, 2015
Last Update Posted: October 21, 2015
Last Verified: October 2015

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

Additional relevant MeSH terms:
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action