Trial Outcomes & Findings for Study Evaluating the Pharmacokinetic and Mass Balance of Single Dose [14C] AZD9291 in Volunteers (NCT NCT02096679)
NCT ID: NCT02096679
Last Updated: 2015-10-21
Results Overview
The percentage of radioactive dose of \[14C\] radiolabelled AZD9291 recovered in urine, faeces, and in total, up to Day 85.
COMPLETED
PHASE1
8 participants
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.
2015-10-21
Participant Flow
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.
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
Participant milestones
| Measure |
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
|
|---|---|
|
Overall Study
STARTED
|
8
|
|
Overall Study
COMPLETED
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study Evaluating the Pharmacokinetic and Mass Balance of Single Dose [14C] AZD9291 in Volunteers
Baseline characteristics by cohort
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Age, Continuous
|
42 Years
STANDARD_DEVIATION 13 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.Population: 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
The percentage of radioactive dose of \[14C\] radiolabelled AZD9291 recovered in urine, faeces, and in total, up to Day 85.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Percentage of Radioactive Dose of [14C] Radiolabelled AZD9291 Recovered in Urine, Faeces, and in Total.
Urine
|
14.2 Percentage radioactive dose recovered
Standard Deviation 2.08
|
|
Percentage of Radioactive Dose of [14C] Radiolabelled AZD9291 Recovered in Urine, Faeces, and in Total.
Faeces
|
67.8 Percentage radioactive dose recovered
Standard Deviation 4.35
|
|
Percentage of Radioactive Dose of [14C] Radiolabelled AZD9291 Recovered in Urine, Faeces, and in Total.
Total
|
81.9 Percentage radioactive dose recovered
Standard Deviation 4.41
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
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)
AZD9291
|
1580 nM*h
Full Range 17.7 • Interval 799.0 to 2480.0
|
|
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)
AZ5104
|
125 nM*h
Full Range 17.4 • Interval 93.6 to 234.0
|
|
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)
AZ7550
|
113 nM*h
Full Range 15.6 • Interval 72.3 to 153.0
|
|
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)
[14C] plasma
|
178000 nM*h
Full Range 15.2 • Interval 146000.0 to 227000.0
|
|
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)
[14C] blood
|
158000 nM*h
Full Range 12.8 • Interval 135000.0 to 206000.0
|
SECONDARY outcome
Timeframe: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
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)
AZD9291
|
1010 nM*h
Full Range 17.7 • Interval 632.0 to 1490.0
|
|
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)
AZ5104
|
72.1 nM*h
Full Range 17.4 • Interval 53.8 to 108.0
|
|
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)
AZ7550
|
50.9 nM*h
Full Range 15.6 • Interval 40.9 to 64.0
|
|
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)
[14C] plasma
|
9670 nM*h
Full Range 15.2 • Interval 8060.0 to 12200.0
|
|
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)
[14C] blood
|
10700 nM*h
Full Range 12.8 • Interval 8240.0 to 13200.0
|
SECONDARY outcome
Timeframe: Blood samples (hrs) - 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
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)
AZD9291
|
444 nM*h
Full Range 17.7 • Interval 318.0 to 632.0
|
|
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)
AZ5104
|
24.4 nM*h
Full Range 17.4 • Interval 17.3 to 36.6
|
|
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)
AZ7550
|
15.7 nM*h
Full Range 15.6 • Interval 12.1 to 20.5
|
|
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)
[14C] plasma
|
1980 nM*h
Full Range 15.2 • Interval 1630.0 to 2420.0
|
|
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)
[14C] blood
|
2300 nM*h
Full Range 12.8 • Interval 1840.0 to 2740.0
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Maximum Plasma Concentration (Cmax)
AZD9291
|
29.9 nM
Full Range 17.7 • Interval 22.3 to 38.5
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Maximum Plasma Concentration (Cmax)
AZ5104
|
1.41 nM
Full Range 17.4 • Interval 0.918 to 2.09
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Maximum Plasma Concentration (Cmax)
AZ7550
|
.957 nM
Full Range 15.6 • Interval 0.804 to 1.34
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Maximum Plasma Concentration (Cmax)
[14C] plasma
|
217 nM
Full Range 15.2 • Interval 189.0 to 280.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Maximum Plasma Concentration (Cmax)
[14C] blood
|
260 nM
Full Range 12.8 • Interval 187.0 to 330.0
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Time to Cmax (Tmax)
AZD9291
|
6 hours
Inter-Quartile Range 17.7 • Interval 6.0 to 8.12
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Time to Cmax (Tmax)
AZ5104
|
6 hours
Inter-Quartile Range 17.4 • Interval 6.0 to 36.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Time to Cmax (Tmax)
AZ7550
|
36 hours
Inter-Quartile Range 15.6 • Interval 6.0 to 48.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Time to Cmax (Tmax)
[14C] plasma
|
144 hours
Inter-Quartile Range 15.2 • Interval 96.0 to 168.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Time to Cmax (Tmax)
[14C] blood
|
132.02 hours
Inter-Quartile Range 12.8 • Interval 96.0 to 168.07
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Lag Time Before Observation of Quantifiable Analyte Concentrations (Tlag)
AZD9291
|
0 hours
Inter-Quartile Range 17.7 • Interval 0.0 to 0.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Lag Time Before Observation of Quantifiable Analyte Concentrations (Tlag)
AZ5104
|
.51 hours
Inter-Quartile Range 17.4 • Interval 0.5 to 1.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Lag Time Before Observation of Quantifiable Analyte Concentrations (Tlag)
AZ7550
|
.76 hours
Inter-Quartile Range 15.6 • Interval 0.0 to 1.5
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Lag Time Before Observation of Quantifiable Analyte Concentrations (Tlag)
[14C] plasma
|
0 hours
Inter-Quartile Range 15.2 • Interval 0.0 to 0.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Lag Time Before Observation of Quantifiable Analyte Concentrations (Tlag)
[14C] blood
|
.25 hours
Inter-Quartile Range 12.8 • Interval 0.0 to 0.5
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Pharmacokinetics of AZD9291 Plasma, Whole Blood and Plasma [14C] Radioactivity by Assessment of Apparent Oral Clearance (CL/F)
AZD9291
|
26.7 L/h
Full Range 17.7 • Interval 16.1 to 49.9
|
|
Pharmacokinetics of AZD9291 Plasma, Whole Blood and Plasma [14C] Radioactivity by Assessment of Apparent Oral Clearance (CL/F)
[14C] plasma
|
.213 L/h
Full Range 15.2 • Interval 0.165 to 0.262
|
|
Pharmacokinetics of AZD9291 Plasma, Whole Blood and Plasma [14C] Radioactivity by Assessment of Apparent Oral Clearance (CL/F)
[14C] blood
|
.231 L/h
Full Range 12.8 • Interval 0.183 to 0.28
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Pharmacokinetics of AZD9291 Plasma, Whole Blood and Plasma [14C] Radioactivity by Assessment of Apparent Volume of Distribution (Vz/F)
AZD9291
|
2260 L
Full Range 17.7 • Interval 1630.0 to 3600.0
|
|
Pharmacokinetics of AZD9291 Plasma, Whole Blood and Plasma [14C] Radioactivity by Assessment of Apparent Volume of Distribution (Vz/F)
[14C] plasma
|
146 L
Full Range 15.2 • Interval 117.0 to 168.0
|
|
Pharmacokinetics of AZD9291 Plasma, Whole Blood and Plasma [14C] Radioactivity by Assessment of Apparent Volume of Distribution (Vz/F)
[14C] blood
|
191 L
Full Range 12.8 • Interval 128.0 to 230.0
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Half-life (t1/2,λz)
AZD9291
|
61.2 hour
Full Range 17.7 • Interval 48.2 to 77.5
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Half-life (t1/2,λz)
AZ5104
|
55.2 hour
Full Range 17.4 • Interval 41.3 to 77.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Half-life (t1/2,λz)
AZ7550
|
82 hour
Full Range 15.6 • Interval 60.2 to 100.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Half-life (t1/2,λz)
[14C] plasma
|
474 hour
Full Range 15.2 • Interval 415.0 to 537.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Half-life (t1/2,λz)
[14C] blood
|
562 hour
Full Range 12.8 • Interval 477.0 to 685.0
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Rate Constant (λz)
AZD9291
|
.0115 1/h
Full Range 17.7 • Interval 0.00894 to 0.0144
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Rate Constant (λz)
AZ5104
|
.0129 1/h
Full Range 17.4 • Interval 0.00901 to 0.0168
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Rate Constant (λz)
AZ7550
|
.00854 1/h
Full Range 15.6 • Interval 0.00692 to 0.0115
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Rate Constant (λz)
[14C] plasma
|
.00147 1/h
Full Range 15.2 • Interval 0.00129 to 0.00167
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Elimination Rate Constant (λz)
[14C] blood
|
.00125 1/h
Full Range 12.8 • Interval 0.00101 to 0.00145
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
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)
AZ5104
|
.0909 Ratio
Full Range 17.4 • Interval 0.0566 to 0.18
|
|
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)
AZ7550
|
.0848 Ratio
Full Range 15.6 • Interval 0.0635 to 0.162
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
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)
AZ5104
|
.0471 ratio
Full Range 17.4 • Interval 0.0346 to 0.0937
|
|
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)
AZ7550
|
.0319 ratio
Full Range 15.6 • Interval 0.0232 to 0.0502
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
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))
AZD9291
|
.138 ratio
Full Range 17.7 • Interval 0.117 to 0.199
|
|
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))
AZ5104
|
.00648 ratio
Full Range 17.4 • Interval 0.00421 to 0.0109
|
|
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))
AZ7550
|
.0044 ratio
Full Range 15.6 • Interval 0.00328 to 0.00586
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
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)
|
1.2 ratio
Full Range 12.8 • Interval 0.984 to 1.65
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
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)
AZD9291
|
.00826 ratio
Full Range 17.4 • Interval 0.00429 to 0.0163
|
|
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)
AZ5104
|
.000751 ratio
Full Range 15.6 • Interval 0.000508 to 0.00158
|
|
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)
AZ7550
|
.000698 ratio
Full Range 15.2 • Interval 0.000566 to 0.00103
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
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))
|
.917 ratio
Full Range 12.8 • Interval 0.809 to 1.06
|
SECONDARY outcome
Timeframe: 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.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve AUC
AZD9291
|
1590 nM*h
Full Range 17.7 • Interval 803.0 to 2490.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve AUC
AZ5104
|
143 nM*h
Full Range 17.4 • Interval 106.0 to 242.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve AUC
AZ7550
|
132 nM*h
Full Range 15.6 • Interval 92.5 to 170.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve AUC
[14C] plasma
|
190000 nM*h
Full Range 15.2 • Interval 153000.0 to 242000.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Whole Blood and Plasma [14C] Radioactivity by Assessment of Area Under the Concentration-time Curve AUC
[14C] blood
|
174000 nM*h
Full Range 12.8 • Interval 143000.0 to 219000.0
|
SECONDARY outcome
Timeframe: Urine (h): 0-4, 4-8, 8-12, 12-24, every 24 hrs to 504, 648-72, 816-40, 984-1008 and 1992-2016.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Pharmacokinetics of AZD9291, Its Metabolites and Urine [14C] Total Radioactivity by Assessment of Urine Concentration or Concentration Equivalent x Urine Volume (Aeu)
AZ7550
|
184 nmol
Standard Deviation 75.4 • Interval 72.3 to 153.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Urine [14C] Total Radioactivity by Assessment of Urine Concentration or Concentration Equivalent x Urine Volume (Aeu)
AZD9291
|
329 nmol
Standard Deviation 133 • Interval 799.0 to 2480.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Urine [14C] Total Radioactivity by Assessment of Urine Concentration or Concentration Equivalent x Urine Volume (Aeu)
AZ5104
|
167 nmol
Standard Deviation 85.8 • Interval 93.6 to 234.0
|
|
Pharmacokinetics of AZD9291, Its Metabolites and Urine [14C] Total Radioactivity by Assessment of Urine Concentration or Concentration Equivalent x Urine Volume (Aeu)
[14C] urine
|
3870 nmol
Standard Deviation 673 • Interval 146000.0 to 227000.0
|
SECONDARY outcome
Timeframe: Urine (h): 0-4, 4-8, 8-12, 12-24, every 24 hrs to 504, 648-72, 816-40, 984-1008 and 1992-2016.Population: 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
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.
Outcome measures
| Measure |
AZD9291 20mg
n=8 Participants
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
|
|---|---|
|
Pharmacokinetics of AZD9291 and Urine [14C] Total Radioactivity by Assessment of Percentage (or Fraction) of Actually Administered Dose / Radioactivity (Feu)
AZD9291
|
.823 Percentage of administered dose
Standard Deviation .332 • Interval 799.0 to 2480.0
|
|
Pharmacokinetics of AZD9291 and Urine [14C] Total Radioactivity by Assessment of Percentage (or Fraction) of Actually Administered Dose / Radioactivity (Feu)
AZ5104
|
.416 Percentage of administered dose
Standard Deviation .214 • Interval 93.6 to 234.0
|
|
Pharmacokinetics of AZD9291 and Urine [14C] Total Radioactivity by Assessment of Percentage (or Fraction) of Actually Administered Dose / Radioactivity (Feu)
AZ7550
|
.460 Percentage of administered dose
Standard Deviation .189 • Interval 72.3 to 153.0
|
|
Pharmacokinetics of AZD9291 and Urine [14C] Total Radioactivity by Assessment of Percentage (or Fraction) of Actually Administered Dose / Radioactivity (Feu)
[14C] urine
|
9.67 Percentage of administered dose
Standard Deviation 1.69 • Interval 146000.0 to 227000.0
|
Adverse Events
AZD9291 20mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AZD9291 20mg
n=8 participants at risk
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
|
|---|---|
|
Eye disorders
Asthenopia
|
12.5%
1/8 • Number of events 1 • From screening through to day 85 (end of study)
|
|
Eye disorders
Visual impairment
|
12.5%
1/8 • Number of events 1 • From screening through to day 85 (end of study)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
12.5%
1/8 • Number of events 1 • From screening through to day 85 (end of study)
|
|
Gastrointestinal disorders
Constipation
|
12.5%
1/8 • Number of events 3 • From screening through to day 85 (end of study)
|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8 • Number of events 1 • From screening through to day 85 (end of study)
|
|
General disorders
Non-cardiac chest pain
|
12.5%
1/8 • Number of events 1 • From screening through to day 85 (end of study)
|
|
Infections and infestations
Otitis media
|
12.5%
1/8 • Number of events 1 • From screening through to day 85 (end of study)
|
|
Injury, poisoning and procedural complications
Laceration
|
12.5%
1/8 • Number of events 1 • From screening through to day 85 (end of study)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.5%
1/8 • Number of events 2 • From screening through to day 85 (end of study)
|
|
Nervous system disorders
Headache
|
25.0%
2/8 • Number of events 5 • From screening through to day 85 (end of study)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
12.5%
1/8 • Number of events 1 • From screening through to day 85 (end of study)
|
|
Vascular disorders
Hot flush
|
12.5%
1/8 • Number of events 1 • From screening through to day 85 (end of study)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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
- Publication restrictions are in place
Restriction type: OTHER