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

Phase 1CompletedNCT02096679

AstraZeneca8 enrolled

Overview

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

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Healthy Volunteers

Interventions

AZD9291DRUG

Volunteer will receive a single oral dose of 20 mg \[14C\]-AZD9291 as a solution on Day 1

Eligibility

Sex: MALEMin age: 30 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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. -

Locations (1)

Research Site

Nottingham, United Kingdom

Outcomes

Primary Outcomes

Percentage of Radioactive Dose of [14C] Radiolabelled AZD9291 Recovered in Urine, Faeces, and in Total.

The percentage of radioactive dose of \[14C\] radiolabelled AZD9291 recovered in urine, faeces, and in total, up to Day 85.

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.

Secondary Outcomes

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)

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.

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 72 Hours AUC(0-72)

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.

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 24 Hours AUC(0-24)

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.

Data from ClinicalTrials.gov

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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 Maximum Plasma Concentration (Cmax)

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.

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 Time to Cmax (Tmax)

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.

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)

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.

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)

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.

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 Volume of Distribution (Vz/F)

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.

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)

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.

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)

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.

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)

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.

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)

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.

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))

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.

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)

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.

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)

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.

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))

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.

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

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.

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 Urine [14C] Total Radioactivity by Assessment of Urine Concentration or Concentration Equivalent x Urine Volume (Aeu)

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.

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)

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.

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.