Trial Outcomes & Findings for Absorption, Metabolism, Excretion and Pharmacokinetics of a Single Dose [14C]AZD2014 Followed by a Multiple Dose Phase (NCT NCT02640755)
NCT ID: NCT02640755
Last Updated: 2019-04-22
Results Overview
The mean CL/F of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
4 participants
Primary outcome timeframe
Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.
Results posted on
2019-04-22
Participant Flow
First subject enrolled: 8 February 2016; Last Subject Last Visit: 21 December 2016 (End of Study \[EoS\]). The study was performed at a single study centre in the United Kingdom. Adult patients with advanced solid tumours refractory or resistant to standard therapies were recruited into this 2 period study.
4 patients were enrolled (signed informed consent). Following \[14C\]-AZD2014, patients either continued AZD2014 as monotherapy or in combination with a standard regimen of fulvestrant or paclitaxel as appropriate and at the Investigator's discretion. No patients were recruited into AZD2014+paclitaxel treatment regimen.
Participant milestones
| Measure |
[14C]-AZD2014 Then AZD2014 Monotherapy
Single Dose Period: Patients were given a single oral dose of radiolabelled AZD2014 (\[14C\]-AZD2014) as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue non-radiolabelled AZD2014 (AZD2014 monotherapy), which was administered as an oral tablet. Patients continued treatment as outpatients until withdrawal due to adverse events (AEs), withdrawal of consent, progression of disease according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Single Dose Period (Day 1 - 8)
STARTED
|
3
|
1
|
|
Single Dose Period (Day 1 - 8)
COMPLETED
|
3
|
1
|
|
Single Dose Period (Day 1 - 8)
NOT COMPLETED
|
0
|
0
|
|
Multiple Dose Period (Day 8 - EoS)
STARTED
|
3
|
1
|
|
Multiple Dose Period (Day 8 - EoS)
COMPLETED
|
1
|
0
|
|
Multiple Dose Period (Day 8 - EoS)
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
[14C]-AZD2014 Then AZD2014 Monotherapy
Single Dose Period: Patients were given a single oral dose of radiolabelled AZD2014 (\[14C\]-AZD2014) as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue non-radiolabelled AZD2014 (AZD2014 monotherapy), which was administered as an oral tablet. Patients continued treatment as outpatients until withdrawal due to adverse events (AEs), withdrawal of consent, progression of disease according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Multiple Dose Period (Day 8 - EoS)
Condition under investigation worsened
|
0
|
1
|
|
Multiple Dose Period (Day 8 - EoS)
Subjective progression of disease
|
1
|
0
|
|
Multiple Dose Period (Day 8 - EoS)
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Absorption, Metabolism, Excretion and Pharmacokinetics of a Single Dose [14C]AZD2014 Followed by a Multiple Dose Phase
Baseline characteristics by cohort
| Measure |
[14C]-AZD2014 Then AZD2014 Monotherapy
n=3 Participants
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue non-radiolabelled AZD2014 (AZD2014 monotherapy), which was administered as an oral tablet. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
n=1 Participants
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
Total
n=4 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32 and 48 hours (h) post [14C]-AZD2014 dose in the Single Dose Period.Population: The Pharmacokinetic (PK) analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean concentrations of total radioactivity in plasma collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 48 hours post-dose. Geometric mean concentrations were not quantifiable after 48 hours. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
0.5 h (n = 3)
|
4013 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 41.55
|
—
|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
1 h (n = 4)
|
3415 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 40.69
|
—
|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
1.5 h (n = 4)
|
2901 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 34.87
|
—
|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
2 h (n = 4)
|
2693 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 36.75
|
—
|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
3 h (n = 4)
|
2105 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 38.82
|
—
|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
4 h (n = 4)
|
1818 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 37.85
|
—
|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
6 h (n = 4)
|
1419 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 37.31
|
—
|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
8 h (n = 4)
|
914.1 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 42.85
|
—
|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
12 h (n = 4)
|
478.6 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 47.42
|
—
|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
24 h (n = 4)
|
97.16 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 35.55
|
—
|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
32 h (n = 4)
|
45.68 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 35.92
|
—
|
|
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014
48 h (n = 3)
|
27.21 nanogram equivalent/millilitre (ngEq/mL)
Geometric Coefficient of Variation 43.22
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean concentrations of AZD2014 in plasma collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 24 hours post-dose. Geometric mean concentrations were not quantifiable after 24 hours.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
0.5 h (n = 3)
|
3704 ng/mL
Geometric Coefficient of Variation 29.79
|
—
|
|
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
1 h (n = 4)
|
3090 ng/mL
Geometric Coefficient of Variation 39.49
|
—
|
|
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
1.5 h (n = 4)
|
2758 ng/mL
Geometric Coefficient of Variation 26.33
|
—
|
|
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
2 h (n = 4)
|
2409 ng/mL
Geometric Coefficient of Variation 22.11
|
—
|
|
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
3 h (n = 4)
|
1768 ng/mL
Geometric Coefficient of Variation 26.45
|
—
|
|
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
4 h (n = 4)
|
1439 ng/mL
Geometric Coefficient of Variation 43.74
|
—
|
|
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
6 h (n = 4)
|
917.7 ng/mL
Geometric Coefficient of Variation 8.278
|
—
|
|
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
8 h (n = 4)
|
619.4 ng/mL
Geometric Coefficient of Variation 40.08
|
—
|
|
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
12 h (n = 4)
|
314.6 ng/mL
Geometric Coefficient of Variation 67.36
|
—
|
|
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014
24 h (n = 2)
|
35.11 ng/mL
Geometric Coefficient of Variation 103.2
|
—
|
PRIMARY outcome
Timeframe: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean concentrations of total radioactivity in saliva collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of saliva collection up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total \[14C\] radioactivity in saliva was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014
1 h (n = 2)
|
5495 ngEq/mL
Geometric Coefficient of Variation 89.69
|
—
|
|
Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014
2 h (n = 3)
|
650.2 ngEq/mL
Geometric Coefficient of Variation 52.98
|
—
|
|
Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014
4 h (n = 3)
|
264.3 ngEq/mL
Geometric Coefficient of Variation 62.10
|
—
|
|
Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014
6 h (n = 3)
|
135.4 ngEq/mL
Geometric Coefficient of Variation 73.87
|
—
|
|
Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014
8 h (n = 3)
|
158.5 ngEq/mL
Geometric Coefficient of Variation 33.15
|
—
|
|
Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014
10 h (n = 3)
|
105.2 ngEq/mL
Geometric Coefficient of Variation 39.57
|
—
|
|
Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014
12 h (n = 3)
|
104.0 ngEq/mL
Geometric Coefficient of Variation 48.01
|
—
|
PRIMARY outcome
Timeframe: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean concentrations of AZD2014 in saliva collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014
1 h (n = 3)
|
4159 ng/mL
Geometric Coefficient of Variation 84.68
|
—
|
|
AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014
2 h (n = 4)
|
416.3 ng/mL
Geometric Coefficient of Variation 84.85
|
—
|
|
AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014
4 h (n = 4)
|
169.1 ng/mL
Geometric Coefficient of Variation 52.50
|
—
|
|
AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014
6 h (n = 4)
|
75.08 ng/mL
Geometric Coefficient of Variation 40.23
|
—
|
|
AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014
8 h (n = 4)
|
73.27 ng/mL
Geometric Coefficient of Variation 15.19
|
—
|
|
AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014
10 h (n = 3)
|
32.59 ng/mL
Geometric Coefficient of Variation 60.47
|
—
|
|
AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014
12 h (n = 2)
|
33.96 ng/mL
Geometric Coefficient of Variation 69.25
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean concentrations of total radioactivity in blood collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of blood sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014
0.5 h (n = 3)
|
2725 ngEq/mL
Geometric Coefficient of Variation 38.13
|
—
|
|
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014
1 h (n = 4)
|
2293 ngEq/mL
Geometric Coefficient of Variation 42.50
|
—
|
|
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014
1.5 h (n = 4)
|
1980 ngEq/mL
Geometric Coefficient of Variation 36.01
|
—
|
|
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014
2 h (n = 4)
|
1783 ngEq/mL
Geometric Coefficient of Variation 36.48
|
—
|
|
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014
3 h (n = 4)
|
1421 ngEq/mL
Geometric Coefficient of Variation 38.64
|
—
|
|
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014
4 h (n = 4)
|
1255 ngEq/mL
Geometric Coefficient of Variation 37.07
|
—
|
|
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014
6 h (n = 4)
|
964.9 ngEq/mL
Geometric Coefficient of Variation 39.01
|
—
|
|
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014
8 h (n = 4)
|
632.1 ngEq/mL
Geometric Coefficient of Variation 43.65
|
—
|
|
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014
12 h (n = 4)
|
345.0 ngEq/mL
Geometric Coefficient of Variation 44.17
|
—
|
PRIMARY outcome
Timeframe: From pre-dose Day 1 to Day 8 of the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean cumulative percentage of \[14C\]-AZD2014 dose recovered as total radioactivity by the end of the Single Dose Period (Day 1 - 8) is presented. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=3 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Cumulative Percentage of [14C]-AZD2014 Recovered by Day 8
|
92.02 Percentage of dose administered
Standard Deviation 1.994
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
Mean AZD2014 Cmax values in plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva
Cmax in plasma
|
4254 ng/mL
Geometric Coefficient of Variation 37.73
|
—
|
|
Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva
Cmax in saliva
|
5410 ng/mL
Geometric Coefficient of Variation 94.34
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
AZD2014 Tmax values for plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva
Tmax in plasma
|
0.53 h
Full Range 37.73 • Interval 0.5 to 0.57
|
—
|
|
Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva
Tmax in saliva
|
1.00 h
Interval 0.98 to 1.17
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
AZD2014 t(last) values in plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva
t(last) in plasma
|
17.04 h
Geometric Coefficient of Variation 41.33
|
—
|
|
Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva
t(last) in saliva
|
10.57 h
Geometric Coefficient of Variation 21.76
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
Mean AUC for AZD2014 following administration of \[14C\]-AZD2014 on Day 1 is presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC) for AZD2014
|
17170 h*ng/mL
Geometric Coefficient of Variation 29.80
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
Mean AUC(0-t) values in plasma and saliva for AZD2014 following administration of \[14C\]-AZD2014 on Day 1 are presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva
AUC(0-t) in plasma
|
16510 h*ng/mL
Geometric Coefficient of Variation 29.31
|
—
|
|
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva
AUC(0-t) in saliva
|
6025 h*ng/mL
Geometric Coefficient of Variation 78.70
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean CL/F of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Apparent Total Body Clearance (CL/F) of AZD2014
|
7.282 L/h
Geometric Coefficient of Variation 29.80
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The MRT of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Mean Residence Time (MRT) of AZD2014
|
5.200 h
Geometric Coefficient of Variation 27.98
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean Vss/F of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Apparent Volume of Distribution at Steady State (Vss/F) for AZD2014 in Plasma
|
37.86 L
Geometric Coefficient of Variation 31.68
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean lambda\_z of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Terminal Elimination Rate Constant (lambda_z) for AZD2014 in Plasma
|
0.1941 1/h
Geometric Coefficient of Variation 32.54
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h ost [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean t1/2(lambda\_z) for AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Half-life Associated With Terminal Slope (lambda_z) of a Semi-logarithmic Concentration-time Curve (t1/2[lambda_z]) for AZD2014 in Plasma
|
3.571 h
Geometric Coefficient of Variation 32.54
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
Mean \[14C\] radioactivity Cmax values in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Cmax for Total [14C] Radioactivity in Whole Blood and Saliva
Cmax in saliva
|
6966 ngEq/mL
Geometric Coefficient of Variation 76.90
|
—
|
|
Cmax for Total [14C] Radioactivity in Whole Blood and Saliva
Cmax in whole blood
|
3004 ngEq/mL
Geometric Coefficient of Variation 36.91
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
\[14C\] radioactivity tmax in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 is presented .
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Tmax for [14C] Radioactivity in Whole Blood and Saliva
tmax in whole blood
|
0.53 h
Full Range 37.73 • Interval 0.5 to 0.57
|
—
|
|
Tmax for [14C] Radioactivity in Whole Blood and Saliva
tmax in saliva
|
1.00 h
Interval 0.98 to 1.17
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
Mean \[14C\] radioactivity t(last) values in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
T(Last) for [14C] Radioactivity in Whole Blood and Saliva
t(last) in whole blood
|
18.26 h
Geometric Coefficient of Variation 53.16
|
—
|
|
T(Last) for [14C] Radioactivity in Whole Blood and Saliva
t(last) in saliva
|
15.33 h
Geometric Coefficient of Variation 39.24
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean ratios of whole blood total radioactivity to plasma total radioactivity are presented for the timepoints of sample collection up to 12 hours post-dose. Geometric mean ratios were not calculated after 12 hours.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity
0.5 h
|
0.6861 ngEq/mL:ngEq/mL
Geometric Coefficient of Variation 8.213
|
—
|
|
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity
1 h
|
0.6713 ngEq/mL:ngEq/mL
Geometric Coefficient of Variation 9.982
|
—
|
|
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity
1.5 h
|
0.6825 ngEq/mL:ngEq/mL
Geometric Coefficient of Variation 7.089
|
—
|
|
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity
2 h
|
0.6623 ngEq/mL:ngEq/mL
Geometric Coefficient of Variation 5.377
|
—
|
|
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity
3 h
|
0.6750 ngEq/mL:ngEq/mL
Geometric Coefficient of Variation 5.583
|
—
|
|
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity
4 h
|
0.6904 ngEq/mL:ngEq/mL
Geometric Coefficient of Variation 8.647
|
—
|
|
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity
6 h
|
0.6797 ngEq/mL:ngEq/mL
Geometric Coefficient of Variation 7.197
|
—
|
|
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity
8 h
|
0.6917 ngEq/mL:ngEq/mL
Geometric Coefficient of Variation 11.16
|
—
|
|
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity
12 h
|
0.7211 ngEq/mL:ngEq/mL
Geometric Coefficient of Variation 8.798
|
—
|
PRIMARY outcome
Timeframe: Saliva was collected at 1, 2, 4, 6, 8 and 10 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
The mean ratios of saliva AZD2014 to saliva radioactivity concentrations are presented for the timepoints of saliva collection up to 10 hours post-dose. Geometric mean ratios were not calculated after 10 hours. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=3 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva
1 h
|
1.011 ng/mL:ngEq/mL
Geometric Coefficient of Variation 5.350
|
—
|
|
Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva
2 h
|
0.8217 ng/mL:ngEq/mL
Geometric Coefficient of Variation 18.20
|
—
|
|
Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva
4 h
|
0.7001 ng/mL:ngEq/mL
Geometric Coefficient of Variation 6.167
|
—
|
|
Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva
6 h
|
0.4993 ng/mL:ngEq/mL
Geometric Coefficient of Variation 28.85
|
—
|
|
Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva
8 h
|
0.4671 ng/mL:ngEq/mL
Geometric Coefficient of Variation 45.52
|
—
|
|
Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva
10 h
|
0.3648 ng/mL:ngEq/mL
Geometric Coefficient of Variation 21.01
|
—
|
PRIMARY outcome
Timeframe: Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
Mean fe%(R) values per urine collection period are presented as a percentage of the total \[14C\]-AZD2014 dose administered on Day 1.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])
0 - 6 h
|
1.575 % of total [14C]-AZD2014 dose
Standard Deviation 1.165
|
—
|
|
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])
6 - 12 h
|
0.7471 % of total [14C]-AZD2014 dose
Standard Deviation 0.7198
|
—
|
|
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])
12 - 24 h
|
0.3472 % of total [14C]-AZD2014 dose
Standard Deviation 0.3251
|
—
|
|
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])
24 - 48 h
|
0.0460 % of total [14C]-AZD2014 dose
Standard Deviation 0.0697
|
—
|
|
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])
48 - 72 h
|
0 % of total [14C]-AZD2014 dose
Standard Deviation 0
|
—
|
|
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])
72 - 96 h
|
0 % of total [14C]-AZD2014 dose
Standard Deviation 0
|
—
|
|
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])
96 - 120 h
|
0 % of total [14C]-AZD2014 dose
Standard Deviation 0
|
—
|
|
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])
120 - 144 h
|
NA % of total [14C]-AZD2014 dose
Standard Deviation NA
Not calculable due to insufficient number of participants with events (3 reportable values required as a minimum for calculation of a PK parameter).
|
—
|
|
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])
144 - 168 h
|
0 % of total [14C]-AZD2014 dose
Standard Deviation 0
|
—
|
PRIMARY outcome
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
CL(R) of AZD2014 from plasma up to 168 h post-dose.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=4 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Renal Clearance (CL[R]) of AZD2014 From Plasma.
|
0.1596 L/h
Geometric Coefficient of Variation 78.34
|
—
|
PRIMARY outcome
Timeframe: Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
fe cum%(R) by the end of each collection period is presented following administration of \[14C\]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=3 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])
0 - 6 h
|
5.514 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 3.917
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])
0 - 12 h
|
8.990 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 4.711
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])
0 - 24 h
|
11.06 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 5.130
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])
0 - 48 h
|
11.81 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 5.294
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])
0 - 72 h
|
11.96 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 5.378
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])
0 - 96 h
|
12.03 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 5.416
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])
0 - 120 h
|
12.07 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 5.441
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])
0 - 144 h
|
12.07 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 5.441
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])
0 - 168 h
|
12.08 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 5.453
|
—
|
PRIMARY outcome
Timeframe: Stool was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.
fe cum%(f) by the end of each collection period is presented following administration of \[14C\]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=3 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])
0 - 24 h
|
18.23 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 21.55
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])
0 - 48 h
|
52.85 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 5.033
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])
0 - 72 h
|
77.04 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 6.843
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])
0 - 96 h
|
78.59 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 6.029
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])
0 - 120 h
|
79.25 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 5.390
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])
0 - 144 h
|
79.70 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 5.167
|
—
|
|
Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])
0 - 168 h
|
79.94 Cumulative % of total [14C]-AZD2014 dose
Standard Deviation 4.955
|
—
|
SECONDARY outcome
Timeframe: From Day 1 of the Single Dose Period to 30 days after the last dose of AZD2014 administered in the Multiple Dose Period.Population: The safety analysis population consisted of all patients who received at least one dose of AZD2014 (radiolabelled or non-radiolabelled).
AEs (including serious AEs \[SAEs\]) were collected from the time of informed consent (Visit 1) and throughout the study, including the 30-day follow-up. The numbers of patients experiencing any AEs and SAEs, causally related AEs and SAEs, and SAEs which were fatal are presented.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=3 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
n=1 Participants
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Number of AEs Experienced by Patients.
Patients who experienced any AE
|
3 Participants
|
1 Participants
|
|
Number of AEs Experienced by Patients.
Patients who experienced any causally related AE
|
3 Participants
|
1 Participants
|
|
Number of AEs Experienced by Patients.
Patients who experienced any SAE
|
1 Participants
|
1 Participants
|
|
Number of AEs Experienced by Patients.
Patients who experienced any causally related SAE
|
0 Participants
|
0 Participants
|
|
Number of AEs Experienced by Patients.
Patients who experienced fatal SAE
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.Population: The efficacy analysis population consisted of all patients who received at least one dose of study treatment and had a baseline tumour assessment.
Anti-tumour activity through assessment of BOR. BOR was defined for each patient as follows according to the RECIST 1.1 criteria: Complete Response (CR): Disappearance of all target lesions since baseline. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions. Stable Disease (SD): Any cases that do not qualify for either PR or progressive disease (PD). PD: At least a 20% increase in the sum of the diameters of target lesions. BOR for each patient was determined as the best response recorded from the day study treatment started until progression or until the last evaluable RECIST tumour assessment in the absence of progression.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=3 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
n=1 Participants
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Best Overall Response (BOR) Assessment
Response: CR
|
0 Participants
|
0 Participants
|
|
Best Overall Response (BOR) Assessment
Response: PR
|
0 Participants
|
0 Participants
|
|
Best Overall Response (BOR) Assessment
Non-response: SD
|
3 Participants
|
0 Participants
|
|
Best Overall Response (BOR) Assessment
Non-response: Progression
|
0 Participants
|
1 Participants
|
|
Best Overall Response (BOR) Assessment
Non-response: Not evaluable
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.Population: The efficacy analysis population consisted of all patients who received at least one dose of study treatment and had a baseline tumour assessment. Patients with available data are presented.
Assessment of anti-tumour activity through measurement of tumour lesions. Tumour size was defined as the sum of the lengths of the longest diameters of the RECIST 1.1 target lesions.
Outcome measures
| Measure |
[14C]-AZD2014 (Period 1 [Day 1 - 8])
n=3 Participants
125 mg \[14C\]-AZD2014 single oral dose was administered on Day 1. Patients fasted for 2 hours before or 1 hour after administration, and were administered prophylactic anti-emetics.
Samples of whole blood, plasma, urine, faeces, saliva and biofluid (vomit) were collected at various time points up to 168 h post-dose to characterise the absorption, metabolism, excretion and PK of AZD2014.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
n=1 Participants
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Best Percentage Change in Tumour Size From Baseline
|
-8.75 Percentage change in tumour size
Interval -13.0 to -4.5
|
3.1 Percentage change in tumour size
Interval 3.1 to 3.1
|
Adverse Events
[14C]-AZD2014 Then AZD2014 Monotherapy
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
[14C]-AZD2014 Then AZD2014 + Fulvestrant
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
[14C]-AZD2014 Then AZD2014 Monotherapy
n=3 participants at risk
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic predose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue non-radiolabelled AZD2014 (AZD2014 monotherapy), which was administered as an oral tablet. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
n=1 participants at risk
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
General disorders
Malaise
|
33.3%
1/3 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 2 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
Other adverse events
| Measure |
[14C]-AZD2014 Then AZD2014 Monotherapy
n=3 participants at risk
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic predose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue non-radiolabelled AZD2014 (AZD2014 monotherapy), which was administered as an oral tablet. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
[14C]-AZD2014 Then AZD2014 + Fulvestrant
n=1 participants at risk
Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose).
Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.
|
|---|---|---|
|
Infections and infestations
Candida infection
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 2 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Infections and infestations
Lower respiratory tract infection
|
33.3%
1/3 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Infections and infestations
Oral candidiasis
|
33.3%
1/3 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 2 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Blood and lymphatic system disorders
Anaemia
|
33.3%
1/3 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Nervous system disorders
Headache
|
33.3%
1/3 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Nervous system disorders
Mononeuropathy
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Nervous system disorders
Presyncope
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Vascular disorders
Hypotension
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 2 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 2 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Gastrointestinal disorders
Anal inflammation
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Gastrointestinal disorders
Nausea
|
66.7%
2/3 • Number of events 4 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 2 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Gastrointestinal disorders
Stomatitis
|
66.7%
2/3 • Number of events 2 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Gastrointestinal disorders
Vomiting
|
66.7%
2/3 • Number of events 4 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
33.3%
1/3 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
66.7%
2/3 • Number of events 3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Skin and subcutaneous tissue disorders
Onychomadesis
|
33.3%
1/3 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
66.7%
2/3 • Number of events 2 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
33.3%
1/3 • Number of events 2 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Reproductive system and breast disorders
Vulvovaginal dryness
|
33.3%
1/3 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
General disorders
Mucosal inflammation
|
33.3%
1/3 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 2 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Investigations
Neutrophil count decreased
|
33.3%
1/3 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
0.00%
0/1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Investigations
White blood cell count decreased
|
33.3%
1/3 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
|
Injury, poisoning and procedural complications
Stoma site erythema
|
0.00%
0/3 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
100.0%
1/1 • Number of events 1 • TEAEs were collected from first dose of AZD2014 up to 30 days after the last dose. For patients who received AZD2014 monotherapy AEs were collected over approximately 11 months, and over approximately 2 months for those who received AZD2014 + fulvestrant.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER