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

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

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

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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: AZD9291


Participation Criteria
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Eligibility Criteria
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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. -

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Urine (h): 0-4, 4-8, 8-12, 12-24, every 24 hrs to 504, 648-72, 816-40, 984-1008 and 1992-2016. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, healthy, pharmacokinetics, Mass balance