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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [14C]-AZD9291 20mg (oral solution) | Experimental | Volunteers will receive 20 mg [14C]-AZD9291 containing a nominal 1 μCi activity, administered by mouth, as a solution. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD9291 | Drug | Volunteer will receive a single oral dose of 20 mg [14C]-AZD9291 as a solution on Day 1 |
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| 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. |
| 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. |
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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. -
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| Name | Affiliation | Role |
|---|---|---|
| Joanne Collier, MD | Quotient Clinical Ltd, Mere Way, Ruddington Fields, Nottingham, United Kingdom. NG11 6JS | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Nottingham | United Kingdom |
8 evaluable patients were planned to be enrolled. These 8 evaluable patients were assigned to take 20 mg [14C]-AZD9291 oral solution (free base equivalent) containing a nominal dose 1 μCi (0.037 MBq) activity as a single administration on Day 1
8 subjects were recruited into the study, as anticipated in the protocol. All received treatment with 20 mg [14C]-AZD9291 oral solution (free base equivalent) containing a nominal dose 1 μCi (0.037 MBq) activity as a single administration on Day 1 and all completed the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | AZD9291 20mg | 20 mg [14C]-AZD9291 oral solution (free base equivalent) containing a nominal dose 1 μCi (0.037 MBq) activity as a single administration on Day 1 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | AZD9291 20mg | 20 mg [14C]-AZD9291 oral solution (free base equivalent) containing a nominal dose 1 μCi (0.037 MBq) activity as a single administration on Day 1 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Mean | Standard Deviation | Percentage radioactive dose recovered | 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. |
|
From screening through to day 85 (end of study)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AZD9291 20mg | 20 mg [14C]-AZD9291 oral solution (free base equivalent) containing a nominal dose 1 μCi (0.037 MBq) activity as a single administration on Day 1 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenopia | Eye disorders | MedDRA version 17.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Mireille Cantarini | AstraZeneca | ClinicalTrialTransparency@astrazeneca.com |
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| ID | Term |
|---|---|
| C000596361 | osimertinib |
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| 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. |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | nM*h | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | nM*h | Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72 |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | nM*h | Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | nM | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Median | Inter-Quartile Range | hours | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Median | Inter-Quartile Range | hours | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Mean | Full Range | L/h | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Mean | Full Range | L | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Mean | Full Range | hour | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | 1/h | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | Ratio | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | ratio | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | ratio | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | ratio | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | ratio | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | ratio | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Geometric Mean | Full Range | nM*h | 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. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Mean | Standard Deviation | nmol | Urine (h): 0-4, 4-8, 8-12, 12-24, every 24 hrs to 504, 648-72, 816-40, 984-1008 and 1992-2016. |
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| Secondary | 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. | Pharmacokinetic population - all subjects who received 1 dose of [14C]-AZD9291 and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the investigational product | Posted | Mean | Standard Deviation | Percentage of administered dose | Urine (h): 0-4, 4-8, 8-12, 12-24, every 24 hrs to 504, 648-72, 816-40, 984-1008 and 1992-2016. |
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|
| 0 |
| 8 |
| 7 |
| 8 |
| Visual impairment | Eye disorders | MedDRA version 17.0 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 17.0 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA version 17.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version 17.0 | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA version 17.0 | Non-systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA version 17.0 | Non-systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA version 17.0 | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 17.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version 17.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.0 | Non-systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA version 17.0 | Non-systematic Assessment |
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The Principal Investigator (PI) agrees to collaborate on the contents and formation of any publication and to pay due consideration to comments and opinions offered. AstraZeneca have 30 days for final manuscript review and may require that submission for publication be delayed in order to file patent applications
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