Trial Outcomes & Findings for AZD2014 and Fulvestrant in Patients With ER+ Advanced Metastatic Breast Cancer (NCT NCT01597388)

NCT ID: NCT01597388

Last Updated: 2024-12-27

Results Overview

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE1
• Target enrollment: 99 participants
• Primary outcome timeframe: Up to 12 Months
• Results posted on: 2024-12-27

Participant Flow

One hundred ten (110) patients enrolled in the study; 100 patients were assigned to a treatment schedule and 10 patients were screen failures. One patient withdrew from the study prior to receiving study drug and was excluded from the safety analysis set. Patients were treated at 5 sites in the US from 21 May 2012 until 4 August 2016.

Participant milestones

Measure	35 mg BID Continuous Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous Participants took 75 mg of AZD2014 one time each day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycles.	100 mg QD Continuous Participants took 100 mg of AZD2014 one time each day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycles.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Overall Study STARTED	6	13	14	10	37	4	8	5	2
Overall Study COMPLETED	6	13	14	10	37	4	8	5	2
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

AZD2014 and Fulvestrant in Patients With ER+ Advanced Metastatic Breast Cancer

Baseline characteristics by cohort

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time each day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycles.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time each day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycles.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	Total n=99 Participants Total of all reporting groups
Age, Continuous	58.5 Years n=5 Participants	64.0 Years n=7 Participants	61.0 Years n=5 Participants	62.0 Years n=4 Participants	61.0 Years n=21 Participants	55.0 Years n=8 Participants	55.5 Years n=8 Participants	59.0 Years n=24 Participants	55.0 Years n=42 Participants	61.0 Years n=42 Participants
Age, Customized ≥18 and <50 years	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	7 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants	13 Participants n=42 Participants
Age, Customized ≥50 to <65 years	3 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	5 Participants n=4 Participants	18 Participants n=21 Participants	4 Participants n=8 Participants	7 Participants n=8 Participants	3 Participants n=24 Participants	0 Participants n=42 Participants	54 Participants n=42 Participants
Age, Customized ≥65 years	2 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	12 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants	32 Participants n=42 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	13 Participants n=7 Participants	14 Participants n=5 Participants	10 Participants n=4 Participants	37 Participants n=21 Participants	4 Participants n=8 Participants	8 Participants n=8 Participants	5 Participants n=24 Participants	2 Participants n=42 Participants	99 Participants n=42 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	24 Participants n=21 Participants	4 Participants n=8 Participants	5 Participants n=8 Participants	4 Participants n=24 Participants	2 Participants n=42 Participants	42 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	9 Participants n=4 Participants	13 Participants n=21 Participants	0 Participants n=8 Participants	3 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	56 Participants n=42 Participants
Race/Ethnicity, Customized White	6 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	10 Participants n=4 Participants	35 Participants n=21 Participants	2 Participants n=8 Participants	7 Participants n=8 Participants	5 Participants n=24 Participants	2 Participants n=42 Participants	90 Participants n=42 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	8 Participants n=42 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Region of Enrollment United States	6 Participants n=5 Participants	13 Participants n=7 Participants	14 Participants n=5 Participants	10 Participants n=4 Participants	37 Participants n=21 Participants	4 Participants n=8 Participants	8 Participants n=8 Participants	5 Participants n=24 Participants	2 Participants n=42 Participants	99 Participants n=42 Participants
Weight	77.42 kg STANDARD_DEVIATION 15.953 • n=5 Participants	73.29 kg STANDARD_DEVIATION 18.845 • n=7 Participants	74.51 kg STANDARD_DEVIATION 19.236 • n=5 Participants	74.53 kg STANDARD_DEVIATION 23.776 • n=4 Participants	67.62 kg STANDARD_DEVIATION 15.511 • n=21 Participants	79.88 kg STANDARD_DEVIATION 17.854 • n=8 Participants	68.95 kg STANDARD_DEVIATION 14.115 • n=8 Participants	77.98 kg STANDARD_DEVIATION 12.586 • n=24 Participants	77.45 kg STANDARD_DEVIATION NA • n=42 Participants	71.96 kg STANDARD_DEVIATION 17.134 • n=42 Participants
ECOG Performance Status (PS) PS = 0	3 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	5 Participants n=4 Participants	16 Participants n=21 Participants	2 Participants n=8 Participants	5 Participants n=8 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants	52 Participants n=42 Participants
ECOG Performance Status (PS) PS = 1	3 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	21 Participants n=21 Participants	2 Participants n=8 Participants	3 Participants n=8 Participants	4 Participants n=24 Participants	1 Participants n=42 Participants	47 Participants n=42 Participants
ECOG Performance Status (PS) PS = 2	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
ECOG Performance Status (PS) PS = 3	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
ECOG Performance Status (PS) PS = 4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Tumour Grade G1	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	4 Participants n=42 Participants
Tumour Grade G2	3 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	14 Participants n=21 Participants	1 Participants n=8 Participants	2 Participants n=8 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants	39 Participants n=42 Participants
Tumour Grade G3	1 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	8 Participants n=21 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants	2 Participants n=24 Participants	1 Participants n=42 Participants	23 Participants n=42 Participants
Tumour Grade G4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Tumour Grade Gx	1 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	1 Participants n=4 Participants	10 Participants n=21 Participants	1 Participants n=8 Participants	4 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	25 Participants n=42 Participants
Tumour Grade Missing	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	7 Participants n=42 Participants
Histology Type Cannot be determined	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Histology Type Invasive carcinoma (NOS)	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	8 Participants n=42 Participants
Histology Type Invasive ductal	4 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	5 Participants n=4 Participants	17 Participants n=21 Participants	1 Participants n=8 Participants	5 Participants n=8 Participants	4 Participants n=24 Participants	1 Participants n=42 Participants	50 Participants n=42 Participants
Histology Type Invasive ductal/extensive intraductal component	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	4 Participants n=42 Participants
Histology Type Invasive lobular	2 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	9 Participants n=42 Participants
Histology Type Other	0 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	2 Participants n=4 Participants	11 Participants n=21 Participants	2 Participants n=8 Participants	3 Participants n=8 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants	27 Participants n=42 Participants
Malignant pleural effusion Absent	5 Participants n=5 Participants	12 Participants n=7 Participants	14 Participants n=5 Participants	7 Participants n=4 Participants	33 Participants n=21 Participants	1 Participants n=8 Participants	7 Participants n=8 Participants	5 Participants n=24 Participants	2 Participants n=42 Participants	86 Participants n=42 Participants
Malignant pleural effusion Present	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	3 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	13 Participants n=42 Participants
Time from Diagnosis to Enrollment ≤ 6 months	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Time from Diagnosis to Enrollment > 6 to ≤ 12 months	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Time from Diagnosis to Enrollment > 12 to ≤ 24 months	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	6 Participants n=42 Participants
Time from Diagnosis to Enrollment > 24 months	6 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	9 Participants n=4 Participants	33 Participants n=21 Participants	4 Participants n=8 Participants	8 Participants n=8 Participants	5 Participants n=24 Participants	2 Participants n=42 Participants	92 Participants n=42 Participants
Time from most recent progression to enrollment ≤ 3 months	5 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	8 Participants n=4 Participants	28 Participants n=21 Participants	3 Participants n=8 Participants	8 Participants n=8 Participants	5 Participants n=24 Participants	2 Participants n=42 Participants	82 Participants n=42 Participants
Time from most recent progression to enrollment During screening, after informed consent	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants
Time from most recent progression to enrollment > 3 to ≤ 12 months	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	11 Participants n=42 Participants
Time from most recent progression to enrollment > 12 months	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	4 Participants n=42 Participants
Overall disease classification Metastatic	6 Participants n=5 Participants	13 Participants n=7 Participants	14 Participants n=5 Participants	9 Participants n=4 Participants	37 Participants n=21 Participants	4 Participants n=8 Participants	8 Participants n=8 Participants	5 Participants n=24 Participants	2 Participants n=42 Participants	98 Participants n=42 Participants
Overall disease classification Locally advanced	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants
Estrogen Receptor Positive (ER+) Yes	6 Participants n=5 Participants	13 Participants n=7 Participants	14 Participants n=5 Participants	10 Participants n=4 Participants	37 Participants n=21 Participants	4 Participants n=8 Participants	8 Participants n=8 Participants	5 Participants n=24 Participants	2 Participants n=42 Participants	99 Participants n=42 Participants
Estrogen Receptor Positive (ER+) No	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Progesterone Receptor Positive (PR+) Yes	3 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	7 Participants n=4 Participants	30 Participants n=21 Participants	4 Participants n=8 Participants	4 Participants n=8 Participants	1 Participants n=24 Participants	2 Participants n=42 Participants	65 Participants n=42 Participants
Progesterone Receptor Positive (PR+) No	3 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	3 Participants n=4 Participants	7 Participants n=21 Participants	0 Participants n=8 Participants	4 Participants n=8 Participants	4 Participants n=24 Participants	0 Participants n=42 Participants	34 Participants n=42 Participants
Human Epidermal Growth Factor Receptor Positive (HER+) Yes	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants	0 Participants n=8 Participants	2 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	9 Participants n=42 Participants
Human Epidermal Growth Factor Receptor Positive (HER+) No	6 Participants n=5 Participants	12 Participants n=7 Participants	14 Participants n=5 Participants	9 Participants n=4 Participants	33 Participants n=21 Participants	4 Participants n=8 Participants	6 Participants n=8 Participants	4 Participants n=24 Participants	2 Participants n=42 Participants	90 Participants n=42 Participants

PRIMARY outcome

Timeframe: Up to 12 Months

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Adverse Events Any Adverse Event (AE)	6 Participants	13 Participants	14 Participants	10 Participants	37 Participants	4 Participants	8 Participants	5 Participants	2 Participants
Adverse Events Any AE, Causally Related to Fulvestrant Only	2 Participants	3 Participants	6 Participants	3 Participants	12 Participants	0 Participants	2 Participants	0 Participants	1 Participants
Adverse Events AE Outcome of Death, Related to Fulvestrant Only	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Adverse Events Any SAE, Causally Related to AZD2014	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Adverse Events Any AE, Causally Related to AZD2014	5 Participants	12 Participants	14 Participants	9 Participants	35 Participants	4 Participants	8 Participants	5 Participants	2 Participants
Adverse Events Any AE of CTCAE Grade ≥ 3 (G3)	3 Participants	8 Participants	10 Participants	6 Participants	24 Participants	3 Participants	6 Participants	3 Participants	1 Participants
Adverse Events AEs of CTCAE G3, Causally Related to AZD2014	2 Participants	8 Participants	7 Participants	5 Participants	16 Participants	0 Participants	6 Participants	2 Participants	0 Participants
Adverse Events Any AE of CTCAE G3, Related to Fulvestrant Only	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Adverse Events Any Adverse Event with Outcome of Death	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Adverse Events AE with Outcome of Death, Related to AZD2014	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Adverse Events Any Serious Adverse Event (SAE)	0 Participants	1 Participants	3 Participants	1 Participants	7 Participants	0 Participants	3 Participants	1 Participants	0 Participants
Adverse Events Any SAE, Causally Related to Fulvestrant Only	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Adverse Events Any AE Leading to Discontinuation of AZD2014	2 Participants	4 Participants	2 Participants	3 Participants	2 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Adverse Events Any SAE Leading to Discontinuation of AZD2014	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 28 Days

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Adverse Events Leading to Dose Reduction of AZD2014	1 Participants	7 Participants	4 Participants	6 Participants	12 Participants	0 Participants	4 Participants	3 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to 12 Months

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Clinically Important Changes in Haematology Parameters Change in Leukocytes to CTCAE Grade 3 or 4	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Haematology Parameters Change in Lymphocytes ≥ 2 CTCAE Grades	2 Participants	6 Participants	8 Participants	5 Participants	10 Participants	0 Participants	1 Participants	2 Participants	1 Participants
Clinically Important Changes in Haematology Parameters Change in Lymphocytes to CTCAE Grade 3 or 4	0 Participants	3 Participants	3 Participants	0 Participants	7 Participants	1 Participants	1 Participants	1 Participants	1 Participants
Clinically Important Changes in Haematology Parameters Change in Neutrophils ≥ 2 CTCAE Grades	1 Participants	4 Participants	1 Participants	3 Participants	12 Participants	1 Participants	1 Participants	1 Participants	0 Participants
Clinically Important Changes in Haematology Parameters Change in Neutrophils to CTCAE Grade 3 or 4	0 Participants	1 Participants	1 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Haematology Parameters Change in Platelets to CTCAE Grade 3 or 4	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Clinically Important Changes in Haematology Parameters Change in Hemoglobin ≥ 2 CTCAE Grades	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Haematology Parameters Change in Hemoglobin to CTCAE Grade 3 or 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Haematology Parameters Change in Leukocytes ≥ 2 CTCAE Grades	0 Participants	4 Participants	2 Participants	1 Participants	9 Participants	2 Participants	2 Participants	3 Participants	0 Participants
Clinically Important Changes in Haematology Parameters Change in Platelets ≥ 2 CTCAE Grades	0 Participants	0 Participants	2 Participants	0 Participants	2 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Clinically Important Changes in Haematology Parameters Change in aPTT ≥ 2 CTCAE Grades	0 Participants	1 Participants	0 Participants	0 Participants	3 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Clinically Important Changes in Haematology Parameters Change in aPTT to CTCAE Grade 3 or 4	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Clinically Important Changes in Haematology Parameters Change in INR ≥ 2 CTCAE Grades	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Haematology Parameters Change in INR to CTCAE Grade 3 or 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 12 Months

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Clinically Important Changes in Clinical Chemistry Parameters Change in AST to CTCAE Grade 3 or 4	0 Participants	0 Participants	5 Participants	2 Participants	3 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Alk Phosphatase ≥ 2 CTCAE Grades	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Alk Phosphatase to CTCAE Grade 3 or 4	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Albumin ≥ 2 CTCAE Grades	0 Participants	1 Participants	2 Participants	2 Participants	6 Participants	1 Participants	2 Participants	1 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Creatinine ≥ 2 CTCAE Grades	0 Participants	1 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Creatinine to CTCAE Grade 3 or 4	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Phosphate ≥ 2 CTCAE Grades	1 Participants	2 Participants	0 Participants	2 Participants	15 Participants	1 Participants	1 Participants	2 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Phosphate to CTCAE Grade 3 or 4	0 Participants	0 Participants	0 Participants	0 Participants	7 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Urate ≥ 2 CTCAE Grades	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Urate to CTCAE Grade 3 or 4	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Calcium ≥ 2 CTCAE Grades	0 Participants	3 Participants	1 Participants	0 Participants	6 Participants	1 Participants	2 Participants	2 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Calcium to CTCAE Grade 3 or 4	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Sodium ≥ 2 CTCAE Grades	0 Participants	1 Participants	0 Participants	3 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Sodium to CTCAE Grade 3 or 4	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Fasting Glucose to CTCAE Grade 3 or 4	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in NonFasting Glucose ≥ 2 CTCAE Grades	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	2 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Non Fasting Glucose to CTCAE Gr.3 or 4	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in ALT ≥ 2 CTCAE Grades	0 Participants	1 Participants	3 Participants	3 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in ALT to CTCAE Grade 3 or 4	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in AST ≥ 2 CTCAE Grades	0 Participants	2 Participants	3 Participants	2 Participants	2 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Albumin to CTCAE Grade 3 or 4	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Bilirubin ≥ 2 CTCAE Grades	1 Participants	0 Participants	1 Participants	0 Participants	3 Participants	0 Participants	2 Participants	1 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Bilirubin to CTCAE Grade 3 or 4	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Potassium ≥ 2 CTCAE Grades	1 Participants	1 Participants	2 Participants	5 Participants	5 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Potassium to CTCAE Grade 3 or 4	0 Participants	0 Participants	1 Participants	5 Participants	5 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Magnesium ≥ 2 CTCAE Grades	0 Participants	1 Participants	0 Participants	2 Participants	1 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Magnesium to CTCAE Grade 3 or 4	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Clinically Important Changes in Clinical Chemistry Parameters Change in Fasting Glucose ≥ 2 CTCAE Grades	1 Participants	1 Participants	1 Participants	1 Participants	7 Participants	1 Participants	4 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Left Ventricular Ejection Fraction Screening	59.2 % Left Ventricular Ejection Fraction Standard Deviation 4.5	64.0 % Left Ventricular Ejection Fraction Standard Deviation 5.4	60.9 % Left Ventricular Ejection Fraction Standard Deviation 6.2	61.4 % Left Ventricular Ejection Fraction Standard Deviation 9.8	62.6 % Left Ventricular Ejection Fraction Standard Deviation 4.1	62.5 % Left Ventricular Ejection Fraction Standard Deviation 2.9	66.9 % Left Ventricular Ejection Fraction Standard Deviation 4.6	63.8 % Left Ventricular Ejection Fraction Standard Deviation 5.2	NA % Left Ventricular Ejection Fraction Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Left Ventricular Ejection Fraction End of Study	NA % Left Ventricular Ejection Fraction Standard Deviation NA Mean and SD were not calculated because data was available from \< 3 participants.	64.0 % Left Ventricular Ejection Fraction Standard Deviation 2.0	62.3 % Left Ventricular Ejection Fraction Standard Deviation 4.1	61.8 % Left Ventricular Ejection Fraction Standard Deviation 8.3	62.5 % Left Ventricular Ejection Fraction Standard Deviation 2.9	NA % Left Ventricular Ejection Fraction Standard Deviation NA Data not collected	NA % Left Ventricular Ejection Fraction Standard Deviation NA Data not collected	NA % Left Ventricular Ejection Fraction Standard Deviation NA Data not collected	NA % Left Ventricular Ejection Fraction Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Left Ventricular Ejection Fraction Change from Baseline to End of Study	NA % Left Ventricular Ejection Fraction Standard Deviation NA Mean and SD were not	1.4 % Left Ventricular Ejection Fraction Standard Deviation 5.9	-1.5 % Left Ventricular Ejection Fraction Standard Deviation 2.4	0.0 % Left Ventricular Ejection Fraction Standard Deviation 7.6	-1.3 % Left Ventricular Ejection Fraction Standard Deviation 3.9	NA % Left Ventricular Ejection Fraction Standard Deviation NA Data not collected	NA % Left Ventricular Ejection Fraction Standard Deviation NA Data not collected	NA % Left Ventricular Ejection Fraction Standard Deviation NA Data not collected	NA % Left Ventricular Ejection Fraction Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.

PRIMARY outcome

Timeframe: 24 hours

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
QTcF Over 24 Hours Baseline	423.12 msec Standard Deviation 11.070	421.92 msec Standard Deviation 22.715	412.78 msec Standard Deviation 14.222	415.95 msec Standard Deviation 14.849	419.95 msec Standard Deviation 20.502	427.13 msec Standard Deviation 32.995	424.84 msec Standard Deviation 6.932	435.26 msec Standard Deviation 7.971	NA msec Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
QTcF Over 24 Hours 12 Hours Postdose	427.74 msec Standard Deviation 15.157	425.46 msec Standard Deviation 21.533	409.67 msec Standard Deviation 19.176	414.59 msec Standard Deviation 15.760	414.09 msec Standard Deviation 18.188	431.70 msec Standard Deviation 16.896	420.66 msec Standard Deviation 10.462	432.46 msec Standard Deviation 16.503	NA msec Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
QTcF Over 24 Hours 24 Hours Postdose	425.54 msec Standard Deviation 10.519	421.45 msec Standard Deviation 16.339	409.33 msec Standard Deviation 16.313	415.29 msec Standard Deviation 16.968	422.73 msec Standard Deviation 17.900	426.77 msec Standard Deviation 16.591	NA msec Standard Deviation NA Data not collected	NA msec Standard Deviation NA Data not collected	NA msec Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
QTcF Over 24 Hours 0.25 Hours Postdose	429.66 msec Standard Deviation 5.707	420.13 msec Standard Deviation 18.333	413.04 msec Standard Deviation 14.934	418.44 msec Standard Deviation 16.145	NA msec Standard Deviation NA Data not collected	NA msec Standard Deviation NA Data not collected	NA msec Standard Deviation NA Data not collected	NA msec Standard Deviation NA Data not collected	NA msec Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
QTcF Over 24 Hours 0.5 Hours Postdose	431.84 msec Standard Deviation 7.504	419.18 msec Standard Deviation 21.362	415.08 msec Standard Deviation 14.762	418.91 msec Standard Deviation 14.437	413.28 msec Standard Deviation 19.715	418.90 msec Standard Deviation 14.897	415.67 msec Standard Deviation 16.874	420.06 msec Standard Deviation 18.388	NA msec Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
QTcF Over 24 Hours 1 Hour Postdose	431.00 msec Standard Deviation 10.149	422.21 msec Standard Deviation 21.863	416.08 msec Standard Deviation 17.581	416.20 msec Standard Deviation 14.530	416.22 msec Standard Deviation 19.738	427.77 msec Standard Deviation 10.186	419.61 msec Standard Deviation 16.514	421.20 msec Standard Deviation 21.336	NA msec Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
QTcF Over 24 Hours 1.5 Hours Postdose	431.82 msec Standard Deviation 8.569	425.15 msec Standard Deviation 22.106	415.36 msec Standard Deviation 16.394	415.33 msec Standard Deviation 15.020	417.10 msec Standard Deviation 19.672	434.33 msec Standard Deviation 14.199	420.43 msec Standard Deviation 15.627	427.48 msec Standard Deviation 20.863	NA msec Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
QTcF Over 24 Hours 2 Hours Postdose	433.02 msec Standard Deviation 11.921	423.31 msec Standard Deviation 22.678	415.84 msec Standard Deviation 17.508	414.01 msec Standard Deviation 17.988	414.99 msec Standard Deviation 17.250	424.00 msec Standard Deviation 22.528	418.60 msec Standard Deviation 15.144	422.94 msec Standard Deviation 18.036	NA msec Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
QTcF Over 24 Hours 4 Hours Postdose	422.00 msec Standard Deviation 10.583	419.97 msec Standard Deviation 21.322	411.18 msec Standard Deviation 15.886	410.88 msec Standard Deviation 13.815	414.04 msec Standard Deviation 17.351	424.43 msec Standard Deviation 17.832	426.60 msec Standard Deviation 16.724	422.40 msec Standard Deviation 10.397	NA msec Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
QTcF Over 24 Hours 6 Hours Postdose	421.50 msec Standard Deviation 15.453	419.14 msec Standard Deviation 21.269	411.85 msec Standard Deviation 13.387	414.74 msec Standard Deviation 16.413	412.80 msec Standard Deviation 17.342	417.00 msec Standard Deviation 20.421	422.94 msec Standard Deviation 18.577	418.34 msec Standard Deviation 13.781	NA msec Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
QTcF Over 24 Hours 8 Hours Postdose	424.86 msec Standard Deviation 12.688	420.16 msec Standard Deviation 20.437	411.16 msec Standard Deviation 15.587	413.56 msec Standard Deviation 15.072	414.17 msec Standard Deviation 18.533	419.90 msec Standard Deviation 22.274	416.80 msec Standard Deviation 15.144	425.54 msec Standard Deviation 12.246	NA msec Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.

PRIMARY outcome

Timeframe: 28 Days

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Post-Baseline Glucose Elevation Subjects with Max Post-Baseline CTCAE Grade ≥ 2	1 Participants	0 Participants	0 Participants	1 Participants	7 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Post-Baseline Glucose Elevation Subjects with Max Post-Baseline CTCAE Grade ≥ 3	0 Participants	1 Participants	2 Participants	1 Participants	5 Participants	0 Participants	3 Participants	1 Participants	0 Participants
Post-Baseline Glucose Elevation Subjects with Max Post-Baseline CTCAE Grade ≥ 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Post-Baseline Glucose Elevation Participants with ≥ 1 post-baseline elevation	3 Participants	6 Participants	7 Participants	5 Participants	29 Participants	3 Participants	6 Participants	5 Participants	0 Participants
Post-Baseline Glucose Elevation Subjects with Max Post-Baseline CTCAE Grade ≥ 1	2 Participants	5 Participants	5 Participants	3 Participants	17 Participants	2 Participants	2 Participants	4 Participants	0 Participants

PRIMARY outcome

Timeframe: 28 Days

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Sitting Diastolic Blood Pressure Cycle 1, Day 1	74.8 mmHg Standard Deviation 9.43	77.4 mmHg Standard Deviation 9.82	75.4 mmHg Standard Deviation 6.91	76.5 mmHg Standard Deviation 8.03	74.4 mmHg Standard Deviation 11.68	73.8 mmHg Standard Deviation 8.62	75.5 mmHg Standard Deviation 12.32	76.6 mmHg Standard Deviation 8.59	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Sitting Diastolic Blood Pressure Cycle 1, Day 8	74.5 mmHg Standard Deviation 5.96	74.3 mmHg Standard Deviation 8.58	75.3 mmHg Standard Deviation 8.84	72.6 mmHg Standard Deviation 12.68	72.4 mmHg Standard Deviation 11.77	70.8 mmHg Standard Deviation 5.38	78.3 mmHg Standard Deviation 10.64	75.8 mmHg Standard Deviation 7.63	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Sitting Diastolic Blood Pressure Baseline	72.8 mmHg Standard Deviation 7.31	75.4 mmHg Standard Deviation 10.43	77.4 mmHg Standard Deviation 7.71	74.9 mmHg Standard Deviation 8.36	74.4 mmHg Standard Deviation 11.68	73.8 mmHg Standard Deviation 8.62	75.5 mmHg Standard Deviation 13.32	76.6 mmHg Standard Deviation 8.59	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Sitting Diastolic Blood Pressure Cycle 1, Day 15	74.7 mmHg Standard Deviation 2.16	72.8 mmHg Standard Deviation 8.64	75.4 mmHg Standard Deviation 7.86	68.7 mmHg Standard Deviation 7.12	73.1 mmHg Standard Deviation 11.09	70.0 mmHg Standard Deviation 7.87	74.2 mmHg Standard Deviation 14.11	69.0 mmHg Standard Deviation 9.59	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Sitting Diastolic Blood Pressure Cycle 1, Day 22	72.5 mmHg Standard Deviation 7.48	73.9 mmHg Standard Deviation 9.37	76.2 mmHg Standard Deviation 6.20	77.0 mmHg Standard Deviation 5.40	70.9 mmHg Standard Deviation 11.76	74.8 mmHg Standard Deviation 10.24	75.0 mmHg Standard Deviation 12.40	73.2 mmHg Standard Deviation 13.10	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Sitting Diastolic Blood Pressure Cycle 2, Day 1	72.0 mmHg Standard Deviation 8.00	73.3 mmHg Standard Deviation 10.49	72.7 mmHg Standard Deviation 8.91	74.1 mmHg Standard Deviation 7.36	71.4 mmHg Standard Deviation 10.43	73.3 mmHg Standard Deviation 4.57	72.5 mmHg Standard Deviation 12.42	68.0 mmHg Standard Deviation 5.29	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.

PRIMARY outcome

Timeframe: 28 Days

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Sitting Systolic Blood Pressure Cycle 1, Day 8	124.0 mmHg Standard Deviation 5.93	120.4 mmHg Standard Deviation 9.12	123.7 mmHg Standard Deviation 16.41	122.2 mmHg Standard Deviation 20.67	122.2 mmHg Standard Deviation 13.88	115.3 mmHg Standard Deviation 13.30	127.9 mmHg Standard Deviation 17.59	124.8 mmHg Standard Deviation 21.56	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Sitting Systolic Blood Pressure Cycle 1, Day 15	119.7 mmHg Standard Deviation 6.59	115.5 mmHg Standard Deviation 17.50	121.6 mmHg Standard Deviation 17.68	115.2 mmHg Standard Deviation 9.17	122.8 mmHg Standard Deviation 14.96	112.8 mmHg Standard Deviation 13.10	128.3 mmHg Standard Deviation 15.87	126.6 mmHg Standard Deviation 10.97	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Sitting Systolic Blood Pressure Cycle 1, Day 22	116.7 mmHg Standard Deviation 12.09	124.7 mmHg Standard Deviation 16.92	123.5 mmHg Standard Deviation 21.17	125.4 mmHg Standard Deviation 16.67	116.6 mmHg Standard Deviation 16.62	115.5 mmHg Standard Deviation 15.50	119.9 mmHg Standard Deviation 19.18	109.2 mmHg Standard Deviation 8.32	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Sitting Systolic Blood Pressure Cycle 2, Day 1	111.7 mmHg Standard Deviation 17.83	119.7 mmHg Standard Deviation 17.59	123.6 mmHg Standard Deviation 24.89	116.6 mmHg Standard Deviation 10.31	119.3 mmHg Standard Deviation 17.81	112.5 mmHg Standard Deviation 9.00	113.2 mmHg Standard Deviation 18.54	117.0 mmHg Standard Deviation 9.06	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Sitting Systolic Blood Pressure Cycle 1, Day 1	113.5 mmHg Standard Deviation 17.02	125.1 mmHg Standard Deviation 15.68	122.6 mmHg Standard Deviation 18.05	124.7 mmHg Standard Deviation 14.51	124.4 mmHg Standard Deviation 19.04	122.3 mmHg Standard Deviation 14.31	120.8 mmHg Standard Deviation 17.65	137.8 mmHg Standard Deviation 19.18	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Sitting Systolic Blood Pressure Baseline	114.2 mmHg Standard Deviation 9.13	126.3 mmHg Standard Deviation 14.65	127.4 mmHg Standard Deviation 14.09	125.2 mmHg Standard Deviation 20.82	124.4 mmHg Standard Deviation 19.04	122.3 mmHg Standard Deviation 14.31	120.8 mmHg Standard Deviation 17.65	137.8 mmHg Standard Deviation 19.18	NA mmHg Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.

PRIMARY outcome

Timeframe: 28 Days

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Respiratory Rate Baseline	18.3 breaths/min Standard Deviation 2.66	17.5 breaths/min Standard Deviation 1.85	18.3 breaths/min Standard Deviation 1.33	17.8 breaths/min Standard Deviation 2.39	17.5 breaths/min Standard Deviation 0.96	17.5 breaths/min Standard Deviation 0.58	18.1 breaths/min Standard Deviation 0.83	17.6 breaths/min Standard Deviation 0.89	NA breaths/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Respiratory Rate Cycle 1, Day 1	16.0 breaths/min Standard Deviation 1.63	16.6 breaths/min Standard Deviation 1.43	17.7 breaths/min Standard Deviation 1.33	17.3 breaths/min Standard Deviation 1.34	17.5 breaths/min Standard Deviation 0.96	17.5 breaths/min Standard Deviation 0.58	18.1 breaths/min Standard Deviation 0.83	17.6 breaths/min Standard Deviation 0.89	NA breaths/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Respiratory Rate Cycle 1, Day 8	17.3 breaths/min Standard Deviation 1.63	16.4 breaths/min Standard Deviation 1.89	17.6 breaths/min Standard Deviation 1.34	17.5 breaths/min Standard Deviation 0.85	17.2 breaths/min Standard Deviation 1.47	16.8 breaths/min Standard Deviation 0.96	17.3 breaths/min Standard Deviation 1.89	18.0 breaths/min Standard Deviation 0.00	NA breaths/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Respiratory Rate Cycle 1, Day 15	17.2 breaths/min Standard Deviation 0.98	17.1 breaths/min Standard Deviation 1.38	18.5 breaths/min Standard Deviation 1.20	17.9 breaths/min Standard Deviation 1.66	17.6 breaths/min Standard Deviation 1.03	17.0 breaths/min Standard Deviation 0.82	17.7 breaths/min Standard Deviation 0.82	17.4 breaths/min Standard Deviation 0.89	NA breaths/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Respiratory Rate Cycle 1, Day 22	17.3 breaths/min Standard Deviation 2.07	17.8 breaths/min Standard Deviation 1.03	18.0 breaths/min Standard Deviation 1.15	17.1 breaths/min Standard Deviation 1.07	17.6 breaths/min Standard Deviation 1.54	17.8 breaths/min Standard Deviation 1.26	17.6 breaths/min Standard Deviation 0.79	18.0 breaths/min Standard Deviation 0.00	NA breaths/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Respiratory Rate Cycle 2, Day 1	17.3 breaths/min Standard Deviation 1.63	17.6 breaths/min Standard Deviation 1.16	17.8 breaths/min Standard Deviation 0.99	18.3 breaths/min Standard Deviation 1.28	17.3 breaths/min Standard Deviation 2.11	17.8 breaths/min Standard Deviation 1.26	17.3 breaths/min Standard Deviation 1.03	17.5 breaths/min Standard Deviation 1.00	NA breaths/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.

PRIMARY outcome

Timeframe: 28 Days

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Heart Rate Baseline	87.5 beats/min Standard Deviation 11.36	84.5 beats/min Standard Deviation 13.31	82.7 beats/min Standard Deviation 14.14	81.0 beats/min Standard Deviation 13.11	83.5 beats/min Standard Deviation 15.32	73.5 beats/min Standard Deviation 10.75	86.1 beats/min Standard Deviation 21.40	79.6 beats/min Standard Deviation 5.32	NA beats/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Heart Rate Cycle 1, Day 1	87.3 beats/min Standard Deviation 4.92	77.7 beats/min Standard Deviation 14.28	87.3 beats/min Standard Deviation 19.53	86.8 beats/min Standard Deviation 12.90	83.5 beats/min Standard Deviation 15.32	73.5 beats/min Standard Deviation 10.75	86.1 beats/min Standard Deviation 21.40	79.6 beats/min Standard Deviation 5.32	NA beats/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Heart Rate Cycle 1, Day 8	80.8 beats/min Standard Deviation 11.39	81.2 beats/min Standard Deviation 15.93	85.4 beats/min Standard Deviation 19.97	92.6 beats/min Standard Deviation 12.47	84.4 beats/min Standard Deviation 15.61	71.5 beats/min Standard Deviation 6.61	79.4 beats/min Standard Deviation 15.78	75.5 beats/min Standard Deviation 12.01	NA beats/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Heart Rate Cycle 1, Day 15	80.2 beats/min Standard Deviation 9.97	89.3 beats/min Standard Deviation 16.83	86.7 beats/min Standard Deviation 18.48	82.8 beats/min Standard Deviation 8.60	81.3 beats/min Standard Deviation 14.79	83.3 beats/min Standard Deviation 15.33	82.5 beats/min Standard Deviation 17.65	77.4 beats/min Standard Deviation 7.92	NA beats/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Heart Rate Cycle 1, Day 22	82.4 beats/min Standard Deviation 13.58	87.8 beats/min Standard Deviation 16.95	85.3 beats/min Standard Deviation 20.23	86.1 beats/min Standard Deviation 11.18	84.6 beats/min Standard Deviation 17.27	77.8 beats/min Standard Deviation 7.80	87.4 beats/min Standard Deviation 25.97	88.8 beats/min Standard Deviation 11.43	NA beats/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.
Heart Rate Cycle 2, Day 1	83.5 beats/min Standard Deviation 11.81	89.7 beats/min Standard Deviation 11.63	84.0 beats/min Standard Deviation 16.39	87.9 beats/min Standard Deviation 12.45	85.7 beats/min Standard Deviation 15.53	78.0 beats/min Standard Deviation 15.75	83.0 beats/min Standard Deviation 13.94	85.0 beats/min Standard Deviation 12.68	NA beats/min Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm.

PRIMARY outcome

Timeframe: 28 Days

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Body Temperature Baseline	36.35 °C Standard Deviation 0.327	36.44 °C Standard Deviation 0.399	36.46 °C Standard Deviation 0.303	36.48 °C Standard Deviation 0.297	36.57 °C Standard Deviation 0.320	36.60 °C Standard Deviation 0.183	36.39 °C Standard Deviation 0.482	36.40 °C Standard Deviation 0.394	NA °C Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm
Body Temperature Cycle 1, Day 1	36.33 °C Standard Deviation 0.189	36.57 °C Standard Deviation 0.465	36.34 °C Standard Deviation 0.318	36.46 °C Standard Deviation 0.306	36.57 °C Standard Deviation 0.320	36.60 °C Standard Deviation 0.183	36.39 °C Standard Deviation 0.482	36.40 °C Standard Deviation 0.394	NA °C Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm
Body Temperature Cycle 1, Day 8	36.33 °C Standard Deviation 0.308	36.42 °C Standard Deviation 0.217	36.59 °C Standard Deviation 0.493	36.35 °C Standard Deviation 0.372	36.51 °C Standard Deviation 0.370	36.25 °C Standard Deviation 0.129	36.36 °C Standard Deviation 0.276	36.88 °C Standard Deviation 0.359	NA °C Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm
Body Temperature Cycle 1, Day 15	36.48 °C Standard Deviation 0.313	36.74 °C Standard Deviation 0.323	36.45 °C Standard Deviation 0.333	36.35 °C Standard Deviation 0.299	36.50 °C Standard Deviation 0.400	36.30 °C Standard Deviation 0.216	36.77 °C Standard Deviation 0.489	36.42 °C Standard Deviation 0.130	NA °C Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm
Body Temperature Cycle 1, Day 22	36.13 °C Standard Deviation 0.403	36.38 °C Standard Deviation 0.360	36.38 °C Standard Deviation 0.414	36.26 °C Standard Deviation 0.450	36.54 °C Standard Deviation 0.550	36.65 °C Standard Deviation 0.465	36.66 °C Standard Deviation 0.341	36.88 °C Standard Deviation 0.319	NA °C Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm
Body Temperature Cycle 2, Day 1	36.25 °C Standard Deviation 0.315	36.55 °C Standard Deviation 0.238	36.57 °C Standard Deviation 0.312	36.54 °C Standard Deviation 0.444	36.56 °C Standard Deviation 0.292	36.90 °C Standard Deviation 0.294	36.50 °C Standard Deviation 0.456	36.54 °C Standard Deviation 0.152	NA °C Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm

PRIMARY outcome

Timeframe: 28 Days

Population: The analysis population consisted of all participants who received at least one dose of AZD2014.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Oxygen Saturation Cycle 2, Day 1	97.5 % Arterial Oxygen Saturation Standard Deviation 0.55	97.3 % Arterial Oxygen Saturation Standard Deviation 2.09	96.9 % Arterial Oxygen Saturation Standard Deviation 1.26	97.3 % Arterial Oxygen Saturation Standard Deviation 1.04	98.2 % Arterial Oxygen Saturation Standard Deviation 1.39	96.5 % Arterial Oxygen Saturation Standard Deviation 2.52	96.2 % Arterial Oxygen Saturation Standard Deviation 3.31	97.0 % Arterial Oxygen Saturation Standard Deviation 2.16	NA % Arterial Oxygen Saturation Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm
Oxygen Saturation Baseline	97.0 % Arterial Oxygen Saturation Standard Deviation 0.89	97.2 % Arterial Oxygen Saturation Standard Deviation 1.59	96.8 % Arterial Oxygen Saturation Standard Deviation 1.85	96.7 % Arterial Oxygen Saturation Standard Deviation 2.41	97.8 % Arterial Oxygen Saturation Standard Deviation 1.49	97.0 % Arterial Oxygen Saturation Standard Deviation 1.83	97.0 % Arterial Oxygen Saturation Standard Deviation 0.93	97.6 % Arterial Oxygen Saturation Standard Deviation 1.14	NA % Arterial Oxygen Saturation Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm
Oxygen Saturation Cycle 1, Day 1	97.5 % Arterial Oxygen Saturation Standard Deviation 1.00	97.7 % Arterial Oxygen Saturation Standard Deviation 1.90	97.4 % Arterial Oxygen Saturation Standard Deviation 1.16	96.9 % Arterial Oxygen Saturation Standard Deviation 1.90	97.8 % Arterial Oxygen Saturation Standard Deviation 1.49	97.0 % Arterial Oxygen Saturation Standard Deviation 1.83	97.0 % Arterial Oxygen Saturation Standard Deviation 0.93	97.6 % Arterial Oxygen Saturation Standard Deviation 1.14	NA % Arterial Oxygen Saturation Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm
Oxygen Saturation Cycle 1, Day 8	98.3 % Arterial Oxygen Saturation Standard Deviation 1.21	97.5 % Arterial Oxygen Saturation Standard Deviation 1.98	97.1 % Arterial Oxygen Saturation Standard Deviation 1.66	97.1 % Arterial Oxygen Saturation Standard Deviation 1.37	97.8 % Arterial Oxygen Saturation Standard Deviation 1.70	97.0 % Arterial Oxygen Saturation Standard Deviation 2.16	97.7 % Arterial Oxygen Saturation Standard Deviation 1.50	98.3 % Arterial Oxygen Saturation Standard Deviation 2.06	NA % Arterial Oxygen Saturation Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm
Oxygen Saturation Cycle 1, Day 15	97.7 % Arterial Oxygen Saturation Standard Deviation 0.82	96.5 % Arterial Oxygen Saturation Standard Deviation 1.94	97.3 % Arterial Oxygen Saturation Standard Deviation 1.50	97.1 % Arterial Oxygen Saturation Standard Deviation 1.17	98.0 % Arterial Oxygen Saturation Standard Deviation 1.34	97.0 % Arterial Oxygen Saturation Standard Deviation 1.41	97.0 % Arterial Oxygen Saturation Standard Deviation 1.26	96.8 % Arterial Oxygen Saturation Standard Deviation 1.48	NA % Arterial Oxygen Saturation Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm
Oxygen Saturation Cycle 1, Day 22	96.8 % Arterial Oxygen Saturation Standard Deviation 1.72	97.3 % Arterial Oxygen Saturation Standard Deviation 1.82	96.8 % Arterial Oxygen Saturation Standard Deviation 1.77	97.6 % Arterial Oxygen Saturation Standard Deviation 1.51	98.1 % Arterial Oxygen Saturation Standard Deviation 1.63	97.5 % Arterial Oxygen Saturation Standard Deviation 3.11	97.9 % Arterial Oxygen Saturation Standard Deviation 1.57	98.0 % Arterial Oxygen Saturation Standard Deviation 1.63	NA % Arterial Oxygen Saturation Standard Deviation NA Mean and standard deviation were not calculated because there were \< 3 participants in this arm

PRIMARY outcome

Timeframe: 5 Days

Outcome measures

Measure	35 mg BID Continuous n=5 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	971.2 ng/mL Standard Deviation 413.6	1023 ng/mL Standard Deviation 339.4	1895 ng/mL Standard Deviation 965.6	2166 ng/mL Standard Deviation 964.3	—	—	—	—	—

PRIMARY outcome

Timeframe: 5 Days

Outcome measures

Measure	35 mg BID Continuous n=5 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	3478 h*ng/mL Standard Deviation 1398	5080 h*ng/mL Standard Deviation 1985	9723 h*ng/mL Standard Deviation 6408	12590 h*ng/mL Standard Deviation 4900	—	—	—	—	—

PRIMARY outcome

Timeframe: 5 Days

Outcome measures

Measure	35 mg BID Continuous n=5 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	3697 h*ng/mL Standard Deviation 1426	6006 h*ng/mL Standard Deviation 2838	11650 h*ng/mL Standard Deviation 8685	15790 h*ng/mL Standard Deviation 7286	—	—	—	—	—

PRIMARY outcome

Timeframe: 5 Days

Outcome measures

Measure	35 mg BID Continuous n=5 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	3458 h*ng/mL Standard Deviation 1433	5832 h*ng/mL Standard Deviation 2926	11500 h*ng/mL Standard Deviation 8761	15660 h*ng/mL Standard Deviation 7345	—	—	—	—	—

PRIMARY outcome

Timeframe: 5 Days

Outcome measures

Measure	35 mg BID Continuous n=5 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	3731 h*ng/mL Standard Deviation 1412	6392 h*ng/mL Standard Deviation 3350	12360 h*ng/mL Standard Deviation 9950	17360 h*ng/mL Standard Deviation 9479	—	—	—	—	—

PRIMARY outcome

Timeframe: 15 Days

Outcome measures

Measure	35 mg BID Continuous n=33 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=3 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=6 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=5 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	3165 ng/mL Standard Deviation 1052	1933 ng/mL Standard Deviation 793.9	4238 ng/mL Standard Deviation 1440	2454 ng/mL Standard Deviation 838.4	—	—	—	—	—

PRIMARY outcome

Timeframe: 15 Days

Outcome measures

Measure	35 mg BID Continuous n=33 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=3 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=6 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=5 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	1.1 hours Full Range 1052 • Interval 0.5 to 4.0	2.0 hours Full Range 793.9 • Interval 1.07 to 6.15	1.5 hours Full Range 1440 • Interval 0.5 to 8.0	3.0 hours Full Range 838.4 • Interval 1.0 to 4.0	—	—	—	—	—

PRIMARY outcome

Timeframe: 15 Days

Outcome measures

Measure	35 mg BID Continuous n=5 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant	19810 h*ng/mL Standard Deviation 6562	13760 h*ng/mL Standard Deviation 5737	26570 h*ng/mL Standard Deviation 8600	16150 h*ng/mL Standard Deviation 5591	—	—	—	—	—

PRIMARY outcome

Timeframe: 22 Days

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=10 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=11 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=6 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	1374 ng/mL Standard Deviation 447.9	1785 ng/mL Standard Deviation 866	2409 ng/mL Standard Deviation 1305	2327 ng/mL Standard Deviation 1257	—	—	—	—	—

PRIMARY outcome

Timeframe: 22 Days

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=10 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=11 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=6 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	1.3 hours Full Range 447.9 • Interval 0.5 to 4.0	1.0 hours Full Range 866 • Interval 0.5 to 2.0	1.5 hours Full Range 1305 • Interval 0.5 to 6.12	1.5 hours Full Range 1257 • Interval 0.5 to 6.0	—	—	—	—	—

PRIMARY outcome

Timeframe: 15 Days

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=10 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=11 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=6 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant	8611 h*ng/mL Standard Deviation 3864	11810 h*ng/mL Standard Deviation 7107	13510 h*ng/mL Standard Deviation 8937	15580 h*ng/mL Standard Deviation 6024	—	—	—	—	—

SECONDARY outcome

Timeframe: 1 Day

Outcome measures

Measure	35 mg BID Continuous n=5 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.	889.4 ng/mL Geometric Coefficient of Variation 52.72	968.5 ng/mL Geometric Coefficient of Variation 36.45	1678 ng/mL Geometric Coefficient of Variation 55.72	1942 ng/mL Geometric Coefficient of Variation 56.46	—	—	—	—	—

SECONDARY outcome

Timeframe: 1 Day

Outcome measures

Measure	35 mg BID Continuous n=5 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.	1.00 hour Full Range 52.72 • Interval 0.5 to 1.5	1.00 hour Full Range 36.45 • Interval 0.45 to 4.0	1.10 hour Full Range 55.72 • Interval 0.5 to 4.0	1.80 hour Full Range 56.46 • Interval 0.5 to 4.02	—	—	—	—	—

SECONDARY outcome

Timeframe: 1 Day

Outcome measures

Measure	35 mg BID Continuous n=5 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.	3233 h*ng/mL Geometric Coefficient of Variation 46.26 • Interval 0.5 to 1.5	4666 h*ng/mL Geometric Coefficient of Variation 48.2 • Interval 0.45 to 4.0	8185 h*ng/mL Geometric Coefficient of Variation 65.21 • Interval 0.5 to 4.0	11470 h*ng/mL Geometric Coefficient of Variation 53.45 • Interval 0.5 to 4.02	—	—	—	—	—

SECONDARY outcome

Timeframe: 1 Day

Outcome measures

Measure	35 mg BID Continuous n=5 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.	3494 h*ng/mL Geometric Coefficient of Variation 43.96 • Interval 0.5 to 1.5	5543 h*ng/mL Geometric Coefficient of Variation 63.41 • Interval 0.45 to 4.0	9843 h*ng/mL Geometric Coefficient of Variation 75.43 • Interval 0.5 to 4.0	15110 h*ng/mL Geometric Coefficient of Variation 63.32 • Interval 0.5 to 4.02	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 12 months

Population: The population consisted of all patients receiving at least one dose of AZD 2014 and fulvestrant with measurable disease at baseline per RECIST v1.1.

Objective Response Rate (ORR) is defined as the number (%) of patients with a confirmed overall response of either complete response (CR) or partial response (PR).

Outcome measures

Measure	35 mg BID Continuous n=2 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=11 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=13 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=4 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=27 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=3 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=3 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=1 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Objective Response Rate	0 Participants	2 Participants	2 Participants	1 Participants	2 Participants	1 Participants	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: The population consisted of all patients receiving at least one dose of AZD 2014 and fulvestrant with measurable disease at baseline per RECIST v1.1.

Best objective response was the best response a patient had following start of treatment but prior to starting any subsequent cancer therapy and prior to RECIST v1.1 progression or the last evaluable assessment in the absence of RECIST v1.1 progression.

Outcome measures

Measure	35 mg BID Continuous n=2 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=11 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=13 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=4 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=27 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=3 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=3 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=1 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Best Objective Response (BOR) Complete Response	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Best Objective Response (BOR) Partial Response	0 Participants	2 Participants	2 Participants	1 Participants	2 Participants	1 Participants	1 Participants	0 Participants	1 Participants
Best Objective Response (BOR) Stable Disease ≥ 8 weeks	1 Participants	4 Participants	7 Participants	1 Participants	17 Participants	2 Participants	3 Participants	1 Participants	0 Participants
Best Objective Response (BOR) Progression	1 Participants	2 Participants	3 Participants	0 Participants	7 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Best Objective Response (BOR) Not Evaluable	0 Participants	3 Participants	1 Participants	2 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: The number of participants analyzed for Duration of Response is zero in cohorts which had no responders \[35 mg BID Continuous and 170 mg BID Intermittent Days 1 and 2 (fed)\]

Duration of response is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.

Outcome measures

Measure	35 mg BID Continuous Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=2 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=2 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=1 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=1 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=1 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=1 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Duration of Response (DoR)	—	5.1 Months Interval 3.9 to 6.3	9.7 Months Interval 3.3 to 16.0	NA Months Median and interquartile range can not be calculated because there was only one participant in the cohort.	NA Months Interval 3.6 to Median and upper limit of the interquartile range can not be calculated for Duration of Response because response was ongoing for one participant at the time of data cut-off.	NA Months Median and interquartile range can not be calculated because there was only one participant in the cohort.	NA Months Median and interquartile range can not be calculated because there was only one participant in the cohort.	—	10.4 Months Median and interquartile range can not be calculated because there was only one participant in the cohort.

SECONDARY outcome

Timeframe: Up to 12 months

Population: The "tumour assessment" analysis set consisted of all participants who received at least one dose of AZD2014 and fulvestrant and had a baseline tumour assessment.

The Clinical Benefit Rate (CBR) at 24 weeks is defined as the percentage of patients who had a confirmed BOR of CR or PR in the first 24 weeks or who demonstrated SD for a minimum interval of 24 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e., 161 days) following the start of treatment.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=8 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Clinical Benefit Rate (CBR) at 24 Weeks Yes	2 Participants	6 Participants Interval 3.6 to 6.3	4 Participants Interval 3.3 to 16.0	7 Participants Interval 39.1 to 39.1	11 Participants Interval 3.6 to	2 Participants Interval 6.4 to 6.4	3 Participants Interval 12.0 to 12.0	2 Participants	2 Participants Interval 10.4 to 10.4
Clinical Benefit Rate (CBR) at 24 Weeks No	4 Participants	7 Participants	10 Participants	3 Participants	26 Participants	2 Participants	5 Participants	3 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: The "evaluable for response" analysis set consisted of all participants who received at least one dose of AZD2014 and fulvestrant and had measurable disease at baseline per RECIST v1.1.

Baseline was defined as last evaluable assessment prior to starting treatment. Tumour size was the sum of the longest diameters of the target lesions. TLs are measurable tumour lesions.

Outcome measures

Measure	35 mg BID Continuous n=2 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=10 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=12 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=2 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=26 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=3 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=2 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=1 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	NA Percentage Change Standard Deviation NA Mean change in tumour size and standard deviation are not reported when data are available for less than 3 patients.	-9.37 Percentage Change Standard Deviation 39.544	-5.83 Percentage Change Standard Deviation 52.781	NA Percentage Change Standard Deviation NA Mean change in tumour size and standard deviation are not reported when data are available for less than 3 patients.	-0.46 Percentage Change Standard Deviation 28.208	-3.57 Percentage Change Standard Deviation 28.476	-10.96 Percentage Change Standard Deviation 19.012	NA Percentage Change Standard Deviation NA Mean change in tumour size and standard deviation are not reported when data are available for less than 3 patients.	NA Percentage Change Standard Deviation NA Mean change in tumour size and standard deviation are not reported when data are available for less than 3 patients.

SECONDARY outcome

Timeframe: Up to 12 months

Population: The "tumour assessment" analysis set consisted of all participants who received at least one dose of AZD2014 and fulvestrant and had a baseline tumour assessment.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Progression Free Survival	49.4 Weeks 80% Confidence Interval NA • Interval 8.14 to 82.86	35.6 Weeks 80% Confidence Interval 39.544 • Interval 25.57 to 44.43	17.3 Weeks 80% Confidence Interval 52.781 • Interval 16.0 to 21.0	78.3 Weeks 80% Confidence Interval NA • Interval 57.0 to 178.14	22.6 Weeks 80% Confidence Interval 28.208 • Interval 16.14 to 25.14	33.9 Weeks 80% Confidence Interval 28.476 • Interval 17.14 to The upper bound of the 80% C.I. was not a finite number	60.1 Weeks 80% Confidence Interval 19.012 • Interval 16.0 to The upper bound of the 80% C.I. was not a finite number	83.4 Weeks 80% Confidence Interval NA • Interval 7.14 to 83.43	NA Weeks 80% Confidence Interval NA • Interval 61.86 to The median could not be determined because only 1 progression event occurred in this arm. The upper bound of the 80% C.I. was not a finite number

SECONDARY outcome

Timeframe: Up to 12 months

Population: The "tumour assessment" analysis set consisted of all participants who received at least one dose of AZD2014 and fulvestrant and had a baseline tumour assessment.

Outcome measures

Measure	35 mg BID Continuous n=6 Participants Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 Participants Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 Participants Participants took 75 mg of AZD2014 one time per day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	100 mg QD Continuous n=10 Participants Participants took 100 mg of AZD2014 one time per day in 28 day cycles (4 weeks). Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 Participants Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 Participants Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Progression Free Survival at 26 Weeks	33 Percentage 80% Confidence Interval NA • Interval 9.3 to 66.7	38 Percentage 80% Confidence Interval 39.544 • Interval 20.1 to 59.8	21 Percentage 80% Confidence Interval 52.781 • Interval 8.1 to 41.7	60 Percentage 80% Confidence Interval NA • Interval 35.4 to 81.2	35 Percentage 80% Confidence Interval 28.208 • Interval 24.6 to 47.0	50 Percentage 80% Confidence Interval 28.476 • Interval 14.3 to 85.7	38 Percentage 80% Confidence Interval 19.012 • Interval 14.7 to 65.5	40 Percentage 80% Confidence Interval NA • Interval 11.2 to 75.3	100 Percentage 80% Confidence Interval NA • Interval 31.6 to 100.0

Adverse Events

35 mg BID Continuous

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

50 mg BID Continuous

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

75 mg QD Continuous

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

100 mg QD Continuous

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

125 mg BID Intermittent Days 1 and 2 (Fasted)

Serious events: 7 serious events

Other events: 37 other events

Deaths: 0 deaths

125 mg BID Intermittent Days 1 and 2 (Fed)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

170 mg BID Intermittent Days 1 and 2 (Fasted)

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

170 mg BID Intermittent Days 1 and 2 (Fed)

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

125 mg BID Intermittent Days 1 and 4 (Fasted)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	35 mg BID Continuous n=6 participants at risk Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 participants at risk Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 participants at risk Participants took 75 mg of AZD2014 one time each day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycles.	100 mg QD Continuous n=10 participants at risk Participants took 100 mg of AZD2014 one time each day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycles.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 participants at risk Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 participants at risk Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 participants at risk Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 participants at risk Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 participants at risk Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Blood and lymphatic system disorders Evans Syndrome	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Ascities	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Colitis	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Dysphagia	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Enteritis	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Nausea	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	2.7% 1/37 • Number of events 2 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Vomiting	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	2.7% 1/37 • Number of events 2 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
General disorders Fatigue	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Infections and infestations Diverticulitis	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Infections and infestations Pneumonia	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 2 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Infections and infestations Sepsis	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Injury, poisoning and procedural complications Spinal Compression Fracture	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Injury, poisoning and procedural complications Subdural Haematoma	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 2 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Renal and urinary disorders Acute Kidney Injury	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year

Other adverse events

Measure	35 mg BID Continuous n=6 participants at risk Participants took 35 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	50 mg BID Continuous n=13 participants at risk Participants took 50 mg of AZD2014 twice daily continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	75 mg QD Continuous n=14 participants at risk Participants took 75 mg of AZD2014 one time each day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycles.	100 mg QD Continuous n=10 participants at risk Participants took 100 mg of AZD2014 one time each day continuously in 28 day cycles. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycles.	125 mg BID Intermittent Days 1 and 2 (Fasted) n=37 participants at risk Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 2 (Fed) n=4 participants at risk Participants took 125 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fasted) n=8 participants at risk Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	170 mg BID Intermittent Days 1 and 2 (Fed) n=5 participants at risk Participants took 170 mg of AZD2014 twice daily on Days 1 and 2 of each week in 28 day cycles (4 weeks) after eating. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.	125 mg BID Intermittent Days 1 and 4 (Fasted) n=2 participants at risk Participants took 125 mg of AZD2014 twice daily on Days 1 and 4 of each week in 28 day cycles (4 weeks) in a fasted condition. Participants also received intramuscular fulvestrant 500 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle.
Blood and lymphatic system disorders Anaemia	16.7% 1/6 • Number of events 1 • Up to 1 year	23.1% 3/13 • Number of events 3 • Up to 1 year	21.4% 3/14 • Number of events 4 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	8.1% 3/37 • Number of events 4 • Up to 1 year	0.00% 0/4 • Up to 1 year	25.0% 2/8 • Number of events 2 • Up to 1 year	0.00% 0/5 • Up to 1 year	50.0% 1/2 • Number of events 2 • Up to 1 year
Blood and lymphatic system disorders Anaemia of Malignant Disease	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	10.8% 4/37 • Number of events 4 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Blood and lymphatic system disorders Neutropenia	16.7% 1/6 • Number of events 1 • Up to 1 year	7.7% 1/13 • Number of events 2 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	10.8% 4/37 • Number of events 4 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	8.1% 3/37 • Number of events 3 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Eye disorders Vision Blurred	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	0.00% 0/37 • Up to 1 year	0.00% 0/4 • Up to 1 year	25.0% 2/8 • Number of events 2 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Abdominal Distension	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	10.8% 4/37 • Number of events 5 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Abdominal Pain	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	18.9% 7/37 • Number of events 8 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Abdominal Pain, Upper	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	14.3% 2/14 • Number of events 3 • Up to 1 year	0.00% 0/10 • Up to 1 year	13.5% 5/37 • Number of events 5 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Constipation	16.7% 1/6 • Number of events 1 • Up to 1 year	15.4% 2/13 • Number of events 2 • Up to 1 year	14.3% 2/14 • Number of events 3 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	29.7% 11/37 • Number of events 11 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • Number of events 2 • Up to 1 year	61.5% 8/13 • Number of events 8 • Up to 1 year	50.0% 7/14 • Number of events 10 • Up to 1 year	50.0% 5/10 • Number of events 8 • Up to 1 year	51.4% 19/37 • Number of events 26 • Up to 1 year	0.00% 0/4 • Up to 1 year	87.5% 7/8 • Number of events 12 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	100.0% 2/2 • Number of events 2 • Up to 1 year
Gastrointestinal disorders Dry Mouth	16.7% 1/6 • Number of events 1 • Up to 1 year	15.4% 2/13 • Number of events 2 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	20.0% 2/10 • Number of events 3 • Up to 1 year	13.5% 5/37 • Number of events 5 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	40.0% 2/5 • Number of events 3 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Dyspepsia	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	8.1% 3/37 • Number of events 4 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Gastrointestinal disorders Gastrooesophageal Reflux Disease	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	20.0% 2/10 • Number of events 2 • Up to 1 year	16.2% 6/37 • Number of events 7 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Nausea	0.00% 0/6 • Up to 1 year	53.8% 7/13 • Number of events 9 • Up to 1 year	50.0% 7/14 • Number of events 8 • Up to 1 year	90.0% 9/10 • Number of events 15 • Up to 1 year	75.7% 28/37 • Number of events 39 • Up to 1 year	75.0% 3/4 • Number of events 3 • Up to 1 year	100.0% 8/8 • Number of events 15 • Up to 1 year	60.0% 3/5 • Number of events 4 • Up to 1 year	100.0% 2/2 • Number of events 2 • Up to 1 year
Gastrointestinal disorders Oral Pain	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	14.3% 2/14 • Number of events 2 • Up to 1 year	10.0% 1/10 • Number of events 2 • Up to 1 year	21.6% 8/37 • Number of events 11 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Gastrointestinal disorders Stomatitis	50.0% 3/6 • Number of events 4 • Up to 1 year	69.2% 9/13 • Number of events 12 • Up to 1 year	42.9% 6/14 • Number of events 6 • Up to 1 year	70.0% 7/10 • Number of events 10 • Up to 1 year	35.1% 13/37 • Number of events 16 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	50.0% 4/8 • Number of events 6 • Up to 1 year	40.0% 2/5 • Number of events 6 • Up to 1 year	100.0% 2/2 • Number of events 2 • Up to 1 year
Gastrointestinal disorders Vomiting	0.00% 0/6 • Up to 1 year	30.8% 4/13 • Number of events 5 • Up to 1 year	28.6% 4/14 • Number of events 5 • Up to 1 year	30.0% 3/10 • Number of events 4 • Up to 1 year	51.4% 19/37 • Number of events 29 • Up to 1 year	75.0% 3/4 • Number of events 5 • Up to 1 year	100.0% 8/8 • Number of events 18 • Up to 1 year	60.0% 3/5 • Number of events 4 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
General disorders Asthenia	0.00% 0/6 • Up to 1 year	15.4% 2/13 • Number of events 2 • Up to 1 year	21.4% 3/14 • Number of events 3 • Up to 1 year	20.0% 2/10 • Number of events 3 • Up to 1 year	27.0% 10/37 • Number of events 10 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	50.0% 4/8 • Number of events 4 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
General disorders Fatigue	100.0% 3/3 • Number of events 3 • Up to 1 year	53.8% 7/13 • Number of events 13 • Up to 1 year	64.3% 9/14 • Number of events 10 • Up to 1 year	70.0% 7/10 • Number of events 10 • Up to 1 year	62.2% 23/37 • Number of events 24 • Up to 1 year	75.0% 3/4 • Number of events 4 • Up to 1 year	62.5% 5/8 • Number of events 6 • Up to 1 year	80.0% 4/5 • Number of events 5 • Up to 1 year	100.0% 2/2 • Number of events 2 • Up to 1 year
General disorders Oedema Peripheral	16.7% 1/6 • Number of events 1 • Up to 1 year	23.1% 3/13 • Number of events 5 • Up to 1 year	42.9% 6/14 • Number of events 8 • Up to 1 year	0.00% 0/10 • Up to 1 year	18.9% 7/37 • Number of events 7 • Up to 1 year	0.00% 0/4 • Up to 1 year	37.5% 3/8 • Number of events 3 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
General disorders Pain	16.7% 1/6 • Number of events 1 • Up to 1 year	23.1% 3/13 • Number of events 3 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	8.1% 3/37 • Number of events 3 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
General disorders Pyrexia	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 4 • Up to 1 year	21.4% 3/14 • Number of events 3 • Up to 1 year	40.0% 4/10 • Number of events 4 • Up to 1 year	16.2% 6/37 • Number of events 8 • Up to 1 year	0.00% 0/4 • Up to 1 year	25.0% 2/8 • Number of events 2 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Infections and infestations Sinusitis	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	0.00% 0/14 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	0.00% 0/4 • Up to 1 year	37.5% 3/8 • Number of events 4 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Infections and infestations Urinary Tract Infection	33.3% 2/6 • Number of events 2 • Up to 1 year	0.00% 0/13 • Up to 1 year	14.3% 2/14 • Number of events 2 • Up to 1 year	20.0% 2/10 • Number of events 3 • Up to 1 year	21.6% 8/37 • Number of events 10 • Up to 1 year	0.00% 0/4 • Up to 1 year	25.0% 2/8 • Number of events 2 • Up to 1 year	40.0% 2/5 • Number of events 2 • Up to 1 year	0.00% 0/2 • Up to 1 year
Injury, poisoning and procedural complications Fall	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 2 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	5.4% 2/37 • Number of events 2 • Up to 1 year	0.00% 0/4 • Up to 1 year	25.0% 2/8 • Number of events 4 • Up to 1 year	0.00% 0/5 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Investigations Alanine Aminotransferase Increased	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	20.0% 2/10 • Number of events 3 • Up to 1 year	13.5% 5/37 • Number of events 5 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Investigations Aspartate Aminotransferase Increased	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	14.3% 2/14 • Number of events 2 • Up to 1 year	20.0% 2/10 • Number of events 2 • Up to 1 year	21.6% 8/37 • Number of events 9 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Investigations Blood Creatinine Increased	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	14.3% 2/14 • Number of events 2 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	16.2% 6/37 • Number of events 6 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Investigations Breath Sounds Abnormal	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	0.00% 0/14 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	0.00% 0/4 • Up to 1 year	50.0% 4/8 • Number of events 5 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Investigations Transaminases Increased	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	2.7% 1/37 • Number of events 2 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	40.0% 2/5 • Number of events 2 • Up to 1 year	0.00% 0/2 • Up to 1 year
Investigations Weight Decreased	33.3% 2/6 • Number of events 2 • Up to 1 year	15.4% 2/13 • Number of events 2 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	27.0% 10/37 • Number of events 10 • Up to 1 year	50.0% 2/4 • Number of events 2 • Up to 1 year	25.0% 2/8 • Number of events 2 • Up to 1 year	60.0% 3/5 • Number of events 3 • Up to 1 year	0.00% 0/2 • Up to 1 year
Metabolism and nutrition disorders Decreased Appetite	16.7% 1/6 • Number of events 1 • Up to 1 year	38.5% 5/13 • Number of events 5 • Up to 1 year	21.4% 3/14 • Number of events 3 • Up to 1 year	40.0% 4/10 • Number of events 4 • Up to 1 year	40.5% 15/37 • Number of events 16 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	37.5% 3/8 • Number of events 4 • Up to 1 year	60.0% 3/5 • Number of events 3 • Up to 1 year	0.00% 0/2 • Up to 1 year
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • Up to 1 year	30.8% 4/13 • Number of events 5 • Up to 1 year	14.3% 2/14 • Number of events 2 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	16.2% 6/37 • Number of events 6 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/6 • Up to 1 year	23.1% 3/13 • Number of events 5 • Up to 1 year	14.3% 2/14 • Number of events 4 • Up to 1 year	20.0% 2/10 • Number of events 4 • Up to 1 year	13.5% 5/37 • Number of events 9 • Up to 1 year	0.00% 0/4 • Up to 1 year	50.0% 4/8 • Number of events 8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	20.0% 2/10 • Number of events 4 • Up to 1 year	13.5% 5/37 • Number of events 5 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	14.3% 2/14 • Number of events 2 • Up to 1 year	10.0% 1/10 • Number of events 3 • Up to 1 year	18.9% 7/37 • Number of events 11 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	40.0% 2/5 • Number of events 3 • Up to 1 year	0.00% 0/2 • Up to 1 year
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	5.4% 2/37 • Number of events 2 • Up to 1 year	0.00% 0/4 • Up to 1 year	37.5% 3/8 • Number of events 4 • Up to 1 year	20.0% 1/5 • Number of events 2 • Up to 1 year	0.00% 0/2 • Up to 1 year
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	13.5% 5/37 • Number of events 7 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 1/6 • Number of events 1 • Up to 1 year	0.00% 0/13 • Up to 1 year	21.4% 3/14 • Number of events 5 • Up to 1 year	40.0% 4/10 • Number of events 9 • Up to 1 year	16.2% 6/37 • Number of events 6 • Up to 1 year	0.00% 0/4 • Up to 1 year	25.0% 2/8 • Number of events 2 • Up to 1 year	40.0% 2/5 • Number of events 2 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Musculoskeletal and connective tissue disorders Back Pain	33.3% 2/6 • Number of events 2 • Up to 1 year	15.4% 2/13 • Number of events 2 • Up to 1 year	14.3% 2/14 • Number of events 2 • Up to 1 year	20.0% 2/10 • Number of events 2 • Up to 1 year	18.9% 7/37 • Number of events 8 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Musculoskeletal and connective tissue disorders Bone Pain	16.7% 1/6 • Number of events 2 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Musculoskeletal and connective tissue disorders Muscle Spasms	16.7% 1/6 • Number of events 1 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	14.3% 2/14 • Number of events 3 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	8.1% 3/37 • Number of events 3 • Up to 1 year	0.00% 0/4 • Up to 1 year	37.5% 3/8 • Number of events 3 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Musculoskeletal and connective tissue disorders Muscular Weakness	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 2 • Up to 1 year	0.00% 0/14 • Up to 1 year	10.0% 1/10 • Number of events 2 • Up to 1 year	5.4% 2/37 • Number of events 3 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	0.00% 0/14 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	8.1% 3/37 • Number of events 3 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Musculoskeletal and connective tissue disorders Pain in Extremity	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	21.4% 3/14 • Number of events 4 • Up to 1 year	20.0% 2/10 • Number of events 3 • Up to 1 year	16.2% 6/37 • Number of events 7 • Up to 1 year	0.00% 0/4 • Up to 1 year	25.0% 2/8 • Number of events 3 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	50.0% 1/2 • Number of events 2 • Up to 1 year
Nervous system disorders Dizziness	0.00% 0/6 • Up to 1 year	15.4% 2/13 • Number of events 2 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	30.0% 3/10 • Number of events 4 • Up to 1 year	21.6% 8/37 • Number of events 10 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	37.5% 3/8 • Number of events 4 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Nervous system disorders Dysgeusia	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	0.00% 0/14 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	18.9% 7/37 • Number of events 7 • Up to 1 year	50.0% 2/4 • Number of events 2 • Up to 1 year	0.00% 0/8 • Up to 1 year	20.0% 1/5 • Number of events 2 • Up to 1 year	0.00% 0/2 • Up to 1 year
Nervous system disorders Headache	0.00% 0/6 • Up to 1 year	23.1% 3/13 • Number of events 3 • Up to 1 year	14.3% 2/14 • Number of events 2 • Up to 1 year	30.0% 3/10 • Number of events 3 • Up to 1 year	32.4% 12/37 • Number of events 13 • Up to 1 year	0.00% 0/4 • Up to 1 year	50.0% 4/8 • Number of events 9 • Up to 1 year	0.00% 0/5 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Nervous system disorders Peripheral Neuropathy	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	14.3% 2/14 • Number of events 2 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	5.4% 2/37 • Number of events 2 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Psychiatric disorders Anxiety	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	14.3% 2/14 • Number of events 2 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	8.1% 3/37 • Number of events 3 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Psychiatric disorders Confusional State	0.00% 0/6 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	10.8% 4/37 • Number of events 4 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Psychiatric disorders Depression	16.7% 1/6 • Number of events 1 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	8.1% 3/37 • Number of events 3 • Up to 1 year	0.00% 0/4 • Up to 1 year	25.0% 2/8 • Number of events 2 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Psychiatric disorders Insomnia	0.00% 0/6 • Up to 1 year	15.4% 2/13 • Number of events 2 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	10.8% 4/37 • Number of events 4 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Renal and urinary disorders Dysuria	16.7% 1/6 • Number of events 1 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	8.1% 3/37 • Number of events 4 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Reproductive system and breast disorders Pelvic Pain	33.3% 2/6 • Number of events 2 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	5.4% 2/37 • Number of events 2 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Respiratory, thoracic and mediastinal disorders Cough	16.7% 1/6 • Number of events 1 • Up to 1 year	0.00% 0/13 • Up to 1 year	14.3% 2/14 • Number of events 3 • Up to 1 year	40.0% 4/10 • Number of events 8 • Up to 1 year	10.8% 4/37 • Number of events 4 • Up to 1 year	0.00% 0/4 • Up to 1 year	50.0% 4/8 • Number of events 4 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Respiratory, thoracic and mediastinal disorders Dysphonia	16.7% 1/6 • Number of events 1 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	5.4% 2/37 • Number of events 2 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders Dyspnoea, Exertional	16.7% 1/6 • Number of events 1 • Up to 1 year	15.4% 2/13 • Number of events 2 • Up to 1 year	21.4% 3/14 • Number of events 3 • Up to 1 year	20.0% 2/10 • Number of events 2 • Up to 1 year	18.9% 7/37 • Number of events 7 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.00% 0/6 • Up to 1 year	15.4% 2/13 • Number of events 2 • Up to 1 year	0.00% 0/14 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	13.5% 5/37 • Number of events 5 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders Productive Cough	16.7% 1/6 • Number of events 1 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	0.00% 0/14 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	0.00% 0/14 • Up to 1 year	0.00% 0/10 • Up to 1 year	8.1% 3/37 • Number of events 3 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	37.5% 3/8 • Number of events 3 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders Sinus Congestion	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	5.4% 2/37 • Number of events 2 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Respiratory, thoracic and mediastinal disorders Wheezing	16.7% 1/6 • Number of events 1 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	5.4% 2/37 • Number of events 2 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Skin and subcutaneous tissue disorders Alopecia	16.7% 1/6 • Number of events 1 • Up to 1 year	7.7% 1/13 • Number of events 1 • Up to 1 year	14.3% 2/14 • Number of events 3 • Up to 1 year	0.00% 0/10 • Up to 1 year	10.8% 4/37 • Number of events 4 • Up to 1 year	0.00% 0/4 • Up to 1 year	25.0% 2/8 • Number of events 2 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Skin and subcutaneous tissue disorders Dermatitis Acneiform	0.00% 0/6 • Up to 1 year	23.1% 3/13 • Number of events 3 • Up to 1 year	7.1% 1/14 • Number of events 2 • Up to 1 year	0.00% 0/10 • Up to 1 year	5.4% 2/37 • Number of events 2 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 2 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Skin and subcutaneous tissue disorders Dry Skin	50.0% 3/6 • Number of events 3 • Up to 1 year	38.5% 5/13 • Number of events 5 • Up to 1 year	28.6% 4/14 • Number of events 6 • Up to 1 year	10.0% 1/10 • Number of events 1 • Up to 1 year	5.4% 2/37 • Number of events 2 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	25.0% 2/8 • Number of events 2 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	100.0% 2/2 • Number of events 3 • Up to 1 year
Skin and subcutaneous tissue disorders Pruritus	66.7% 4/6 • Number of events 6 • Up to 1 year	46.2% 6/13 • Number of events 9 • Up to 1 year	14.3% 2/14 • Number of events 2 • Up to 1 year	20.0% 2/10 • Number of events 2 • Up to 1 year	16.2% 6/37 • Number of events 6 • Up to 1 year	0.00% 0/4 • Up to 1 year	25.0% 2/8 • Number of events 3 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	100.0% 2/2 • Number of events 2 • Up to 1 year
Skin and subcutaneous tissue disorders Pruritus Generalised	0.00% 0/6 • Up to 1 year	23.1% 3/13 • Number of events 3 • Up to 1 year	0.00% 0/14 • Up to 1 year	20.0% 2/10 • Number of events 2 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • Up to 1 year	23.1% 3/13 • Number of events 5 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	5.4% 2/37 • Number of events 2 • Up to 1 year	25.0% 1/4 • Number of events 1 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Skin and subcutaneous tissue disorders Rash Erythematous	0.00% 0/6 • Up to 1 year	23.1% 3/13 • Number of events 4 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	20.0% 2/10 • Number of events 3 • Up to 1 year	2.7% 1/37 • Number of events 1 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	0.00% 0/5 • Up to 1 year	50.0% 1/2 • Number of events 1 • Up to 1 year
Skin and subcutaneous tissue disorders Rash, Maculo-Papular	33.3% 2/6 • Number of events 2 • Up to 1 year	46.2% 6/13 • Number of events 8 • Up to 1 year	28.6% 4/14 • Number of events 5 • Up to 1 year	20.0% 2/10 • Number of events 2 • Up to 1 year	10.8% 4/37 • Number of events 4 • Up to 1 year	0.00% 0/4 • Up to 1 year	25.0% 2/8 • Number of events 3 • Up to 1 year	0.00% 0/5 • Up to 1 year	100.0% 2/2 • Number of events 2 • Up to 1 year
Vascular disorders Deep Vein Thrombosis	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	5.4% 2/37 • Number of events 2 • Up to 1 year	0.00% 0/4 • Up to 1 year	12.5% 1/8 • Number of events 1 • Up to 1 year	20.0% 1/5 • Number of events 1 • Up to 1 year	0.00% 0/2 • Up to 1 year
Vascular disorders Hypotension	0.00% 0/6 • Up to 1 year	0.00% 0/13 • Up to 1 year	7.1% 1/14 • Number of events 1 • Up to 1 year	0.00% 0/10 • Up to 1 year	16.2% 6/37 • Number of events 7 • Up to 1 year	0.00% 0/4 • Up to 1 year	0.00% 0/8 • Up to 1 year	0.00% 0/5 • Up to 1 year	0.00% 0/2 • Up to 1 year

Additional Information

Julie Charlton

AstraZeneca

Phone: + 01625-582828

Email: ClinicalTrialTransparancy@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place