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

A Phase I, Open-label, Multicentre, Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD2014 Administered Orally in Combination With Intramuscular (IM) Fulvestrant to Patients With Estrogen Receptor Positive (ER+) Advanced, Metastatic Breast Cancer

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01597388

Enrollment

Registered

2012-05-14

Start date

2012-05-08

Completion date

2026-01-13

Last updated

2026-02-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Metastatic Breast Cancer

Keywords

Estrogen receptor positive, Advanced metastatic breast cancer, Estrogen receptor positive advanced metastatic breast cancer

Brief summary

The purpose of this study is to assess safety and tolerability of AZD2014 when given in combination with Fulvestrant

Detailed description

A Phase I, Open-label, Multicentre, Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD2014 Administered Orally in Combination with Intramuscular (IM) Fulvestrant to Patients with Estrogen Receptor Positive (ER+) Advanced, Metastatic Breast Cancer.

Interventions

DRUGAZD2014

Single dose followed by multiple dosing or twice daily dosing for 2 days folllowed by 5 days off each week, or twice daily dosing on the first and fourth day of the week

DRUGFulvestrant

IM monthly after loading dose

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 100 Years

Healthy volunteers

Inclusion criteria

* Provision of signed and dated written informed consent prior to any study specific procedures, sampling analysis * Aged at least 18 * At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computerised tomography (CT) magnetic resonance imaging (MRI) or plain X-ray and is suitable for repeated assessment * Histological or cytological confirmation of an ER+ advanced metastatic breast cancer tumour that is eligible for treatment with fulvestrant * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Patients must have evidence of non-child-bearing potential.

Exclusion criteria

* Prior chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents, and any investigational agents within 14 days of starting study treatment (not including palliative radiotherapy at focal sites) * Major surgery within 4 weeks prior to entry to the study (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study. * Patients with severe cardiac condition of ischemia, impaired ventricular function and arrhythmias, evidence of severe or uncontrolled systemic or current unstable or uncompensated respiratory or cardiac conditions. * Patients with diabetes type 1 or uncontrolled type II (HbA1c \> 8% assessed locally)

Design outcomes

Primary

Measure	Time frame
QTcF Over 24 Hours	24 hours
Post-Baseline Glucose Elevation	28 Days
Sitting Diastolic Blood Pressure	28 Days
Sitting Systolic Blood Pressure	28 Days
Respiratory Rate	28 Days
Heart Rate	28 Days
Body Temperature	28 Days
Oxygen Saturation	28 Days
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5 Days
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	15 Days
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	15 Days
Adverse Events	Up to 12 Months
Adverse Events Leading to Dose Reduction of AZD2014	Up to 28 Days
Clinically Important Changes in Haematology Parameters	Up to 12 Months
Clinically Important Changes in Clinical Chemistry Parameters	Up to 12 Months
Left Ventricular Ejection Fraction	24 hours
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant	15 Days
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	22 Days
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	22 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant	15 Days

Secondary

Measure	Time frame	Description
AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.	1 Day	—
Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.	1 Day	—
Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.	1 Day	—
Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.	1 Day	—
Objective Response Rate	Up to 12 months	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).
Best Objective Response (BOR)	Up to 12 months	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.
Duration of Response (DoR)	Up to 12 months	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.
Clinical Benefit Rate (CBR) at 24 Weeks	Up to 12 months	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.
Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	Up to 12 months	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.
Progression Free Survival	Up to 12 months	—
Progression Free Survival at 26 Weeks	Up to 12 months	—

Countries

United States

Participant flow

Recruitment details

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.

Participants by arm

Arm	Count
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.	6
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.	13
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.	14
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.	10
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.	37
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.	4
170 mg BID Intermittent Days 1 and 2 (Fasted) 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.	8
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.	5
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.	2
Total	99

Baseline characteristics

Characteristic	Total	35 mg BID Continuous	50 mg BID Continuous	75 mg QD Continuous	100 mg QD Continuous	125 mg BID Intermittent Days 1 and 2 (Fasted)	125 mg BID Intermittent Days 1 and 2 (Fed)	170 mg BID Intermittent Days 1 and 2 (Fasted)	170 mg BID Intermittent Days 1 and 2 (Fed)	125 mg BID Intermittent Days 1 and 4 (Fasted)
Age, Continuous	59.9 Years STANDARD_DEVIATION 9.88	58.5 Years	64.0 Years	61.0 Years	62.0 Years	61.0 Years	55.0 Years	55.5 Years	59.0 Years	55.0 Years
Age, Customized ≥18 and <50 years	13 Participants	1 Participants	1 Participants	0 Participants	1 Participants	7 Participants	0 Participants	1 Participants	1 Participants	1 Participants
Age, Customized ≥50 to <65 years	54 Participants	3 Participants	6 Participants	8 Participants	5 Participants	18 Participants	4 Participants	7 Participants	3 Participants	0 Participants
Age, Customized ≥65 years	32 Participants	2 Participants	6 Participants	6 Participants	4 Participants	12 Participants	0 Participants	0 Participants	1 Participants	1 Participants
ECOG Performance Status (PS) PS = 0	52 Participants	3 Participants	11 Participants	8 Participants	5 Participants	16 Participants	2 Participants	5 Participants	1 Participants	1 Participants
ECOG Performance Status (PS) PS = 1	47 Participants	3 Participants	2 Participants	6 Participants	5 Participants	21 Participants	2 Participants	3 Participants	4 Participants	1 Participants
ECOG Performance Status (PS) PS = 2	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
ECOG Performance Status (PS) PS = 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
ECOG Performance Status (PS) PS = 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Estrogen Receptor Positive (ER+) No	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Estrogen Receptor Positive (ER+) Yes	99 Participants	6 Participants	13 Participants	14 Participants	10 Participants	37 Participants	4 Participants	8 Participants	5 Participants	2 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants	0 Participants	1 Participants	2 Participants	0 Participants	24 Participants	4 Participants	5 Participants	4 Participants	2 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	56 Participants	6 Participants	12 Participants	12 Participants	9 Participants	13 Participants	0 Participants	3 Participants	1 Participants	0 Participants
Histology Type Cannot be determined	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Histology Type Invasive carcinoma (NOS)	8 Participants	0 Participants	1 Participants	1 Participants	1 Participants	4 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Histology Type Invasive ductal	50 Participants	4 Participants	6 Participants	7 Participants	5 Participants	17 Participants	1 Participants	5 Participants	4 Participants	1 Participants
Histology Type Invasive ductal/extensive intraductal component	4 Participants	0 Participants	0 Participants	0 Participants	1 Participants	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Histology Type Invasive lobular	9 Participants	2 Participants	3 Participants	1 Participants	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Histology Type Other	27 Participants	0 Participants	2 Participants	5 Participants	2 Participants	11 Participants	2 Participants	3 Participants	1 Participants	1 Participants
Human Epidermal Growth Factor Receptor Positive (HER+) No	90 Participants	6 Participants	12 Participants	14 Participants	9 Participants	33 Participants	4 Participants	6 Participants	4 Participants	2 Participants
Human Epidermal Growth Factor Receptor Positive (HER+) Yes	9 Participants	0 Participants	1 Participants	0 Participants	1 Participants	4 Participants	0 Participants	2 Participants	1 Participants	0 Participants
Malignant pleural effusion Absent	86 Participants	5 Participants	12 Participants	14 Participants	7 Participants	33 Participants	1 Participants	7 Participants	5 Participants	2 Participants
Malignant pleural effusion Present	13 Participants	1 Participants	1 Participants	0 Participants	3 Participants	4 Participants	3 Participants	1 Participants	0 Participants	0 Participants
Overall disease classification Locally advanced	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Overall disease classification Metastatic	98 Participants	6 Participants	13 Participants	14 Participants	9 Participants	37 Participants	4 Participants	8 Participants	5 Participants	2 Participants
Progesterone Receptor Positive (PR+) No	34 Participants	3 Participants	6 Participants	7 Participants	3 Participants	7 Participants	0 Participants	4 Participants	4 Participants	0 Participants
Progesterone Receptor Positive (PR+) Yes	65 Participants	3 Participants	7 Participants	7 Participants	7 Participants	30 Participants	4 Participants	4 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized Black or African American	8 Participants	0 Participants	2 Participants	2 Participants	0 Participants	2 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Other	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized White	90 Participants	6 Participants	11 Participants	12 Participants	10 Participants	35 Participants	2 Participants	7 Participants	5 Participants	2 Participants
Region of Enrollment United States	99 Participants	6 Participants	13 Participants	14 Participants	10 Participants	37 Participants	4 Participants	8 Participants	5 Participants	2 Participants
Sex: Female, Male Female	99 Participants	6 Participants	13 Participants	14 Participants	10 Participants	37 Participants	4 Participants	8 Participants	5 Participants	2 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Time from Diagnosis to Enrollment > 12 to ≤ 24 months	6 Participants	0 Participants	1 Participants	0 Participants	1 Participants	4 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Time from Diagnosis to Enrollment > 24 months	92 Participants	6 Participants	12 Participants	13 Participants	9 Participants	33 Participants	4 Participants	8 Participants	5 Participants	2 Participants
Time from Diagnosis to Enrollment ≤ 6 months	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Time from Diagnosis to Enrollment > 6 to ≤ 12 months	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Time from most recent progression to enrollment > 12 months	4 Participants	0 Participants	1 Participants	0 Participants	0 Participants	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Time from most recent progression to enrollment ≤ 3 months	82 Participants	5 Participants	11 Participants	12 Participants	8 Participants	28 Participants	3 Participants	8 Participants	5 Participants	2 Participants
Time from most recent progression to enrollment > 3 to ≤ 12 months	11 Participants	0 Participants	1 Participants	2 Participants	2 Participants	5 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Time from most recent progression to enrollment During screening, after informed consent	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Tumour Grade G1	4 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Tumour Grade G2	39 Participants	3 Participants	5 Participants	6 Participants	6 Participants	14 Participants	1 Participants	2 Participants	1 Participants	1 Participants
Tumour Grade G3	23 Participants	1 Participants	4 Participants	3 Participants	2 Participants	8 Participants	1 Participants	1 Participants	2 Participants	1 Participants
Tumour Grade G4	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Tumour Grade Gx	25 Participants	1 Participants	3 Participants	5 Participants	1 Participants	10 Participants	1 Participants	4 Participants	0 Participants	0 Participants
Tumour Grade Missing	7 Participants	1 Participants	1 Participants	0 Participants	0 Participants	4 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Weight	71.96 kg STANDARD_DEVIATION 17.134	77.42 kg STANDARD_DEVIATION 15.953	73.29 kg STANDARD_DEVIATION 18.845	74.51 kg STANDARD_DEVIATION 19.236	74.53 kg STANDARD_DEVIATION 23.776	67.62 kg STANDARD_DEVIATION 15.511	79.88 kg STANDARD_DEVIATION 17.854	68.95 kg STANDARD_DEVIATION 14.115	77.98 kg STANDARD_DEVIATION 12.586	77.45 kg

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk
other Total, other adverse events	6 / 6	13 / 13	14 / 14	10 / 10	37 / 37	4 / 4	8 / 8	5 / 5	2 / 2
serious Total, serious adverse events	0 / 6	1 / 13	3 / 14	1 / 10	7 / 37	0 / 4	3 / 8	1 / 5	0 / 2

Outcome results

Primary

Adverse Events

Time frame: Up to 12 Months

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

Arm	Measure	Group	Value (NUMBER)
35 mg BID Continuous	Adverse Events	Any AE Leading to Discontinuation of AZD2014	2 Participants
35 mg BID Continuous	Adverse Events	Any AE of CTCAE G3, Related to Fulvestrant Only	0 Participants
35 mg BID Continuous	Adverse Events	AEs of CTCAE G3, Causally Related to AZD2014	2 Participants
35 mg BID Continuous	Adverse Events	Any SAE Leading to Discontinuation of AZD2014	0 Participants
35 mg BID Continuous	Adverse Events	AE Outcome of Death, Related to Fulvestrant Only	0 Participants
35 mg BID Continuous	Adverse Events	Any AE, Causally Related to Fulvestrant Only	2 Participants
35 mg BID Continuous	Adverse Events	Any AE, Causally Related to AZD2014	5 Participants
35 mg BID Continuous	Adverse Events	Any SAE, Causally Related to Fulvestrant Only	0 Participants
35 mg BID Continuous	Adverse Events	Any Adverse Event with Outcome of Death	0 Participants
35 mg BID Continuous	Adverse Events	Any Adverse Event (AE)	6 Participants
35 mg BID Continuous	Adverse Events	Any Serious Adverse Event (SAE)	0 Participants
35 mg BID Continuous	Adverse Events	Any SAE, Causally Related to AZD2014	0 Participants
35 mg BID Continuous	Adverse Events	AE with Outcome of Death, Related to AZD2014	0 Participants
35 mg BID Continuous	Adverse Events	Any AE of CTCAE Grade ≥ 3 (G3)	3 Participants
50 mg BID Continuous	Adverse Events	Any AE Leading to Discontinuation of AZD2014	4 Participants
50 mg BID Continuous	Adverse Events	Any AE of CTCAE Grade ≥ 3 (G3)	8 Participants
50 mg BID Continuous	Adverse Events	Any SAE, Causally Related to Fulvestrant Only	0 Participants
50 mg BID Continuous	Adverse Events	AEs of CTCAE G3, Causally Related to AZD2014	8 Participants
50 mg BID Continuous	Adverse Events	Any AE, Causally Related to AZD2014	12 Participants
50 mg BID Continuous	Adverse Events	AE Outcome of Death, Related to Fulvestrant Only	0 Participants
50 mg BID Continuous	Adverse Events	Any SAE, Causally Related to AZD2014	0 Participants
50 mg BID Continuous	Adverse Events	Any Adverse Event (AE)	13 Participants
50 mg BID Continuous	Adverse Events	Any SAE Leading to Discontinuation of AZD2014	0 Participants
50 mg BID Continuous	Adverse Events	Any Adverse Event with Outcome of Death	0 Participants
50 mg BID Continuous	Adverse Events	Any AE, Causally Related to Fulvestrant Only	3 Participants
50 mg BID Continuous	Adverse Events	Any Serious Adverse Event (SAE)	1 Participants
50 mg BID Continuous	Adverse Events	AE with Outcome of Death, Related to AZD2014	0 Participants
50 mg BID Continuous	Adverse Events	Any AE of CTCAE G3, Related to Fulvestrant Only	0 Participants
75 mg QD Continuous	Adverse Events	Any SAE, Causally Related to Fulvestrant Only	0 Participants
75 mg QD Continuous	Adverse Events	Any Serious Adverse Event (SAE)	3 Participants
75 mg QD Continuous	Adverse Events	AE Outcome of Death, Related to Fulvestrant Only	0 Participants
75 mg QD Continuous	Adverse Events	Any SAE Leading to Discontinuation of AZD2014	1 Participants
75 mg QD Continuous	Adverse Events	Any AE, Causally Related to AZD2014	14 Participants
75 mg QD Continuous	Adverse Events	Any AE, Causally Related to Fulvestrant Only	6 Participants
75 mg QD Continuous	Adverse Events	Any Adverse Event (AE)	14 Participants
75 mg QD Continuous	Adverse Events	Any AE Leading to Discontinuation of AZD2014	2 Participants
75 mg QD Continuous	Adverse Events	Any AE of CTCAE Grade ≥ 3 (G3)	10 Participants
75 mg QD Continuous	Adverse Events	AEs of CTCAE G3, Causally Related to AZD2014	7 Participants
75 mg QD Continuous	Adverse Events	Any AE of CTCAE G3, Related to Fulvestrant Only	0 Participants
75 mg QD Continuous	Adverse Events	Any SAE, Causally Related to AZD2014	1 Participants
75 mg QD Continuous	Adverse Events	Any Adverse Event with Outcome of Death	1 Participants
75 mg QD Continuous	Adverse Events	AE with Outcome of Death, Related to AZD2014	0 Participants
100 mg QD Continuous	Adverse Events	Any AE Leading to Discontinuation of AZD2014	3 Participants
100 mg QD Continuous	Adverse Events	Any SAE Leading to Discontinuation of AZD2014	0 Participants
100 mg QD Continuous	Adverse Events	Any Adverse Event with Outcome of Death	0 Participants
100 mg QD Continuous	Adverse Events	Any AE of CTCAE G3, Related to Fulvestrant Only	0 Participants
100 mg QD Continuous	Adverse Events	Any Adverse Event (AE)	10 Participants
100 mg QD Continuous	Adverse Events	Any Serious Adverse Event (SAE)	1 Participants
100 mg QD Continuous	Adverse Events	Any AE, Causally Related to AZD2014	9 Participants
100 mg QD Continuous	Adverse Events	Any AE of CTCAE Grade ≥ 3 (G3)	6 Participants
100 mg QD Continuous	Adverse Events	Any SAE, Causally Related to AZD2014	0 Participants
100 mg QD Continuous	Adverse Events	Any SAE, Causally Related to Fulvestrant Only	0 Participants
100 mg QD Continuous	Adverse Events	AE with Outcome of Death, Related to AZD2014	0 Participants
100 mg QD Continuous	Adverse Events	AE Outcome of Death, Related to Fulvestrant Only	0 Participants
100 mg QD Continuous	Adverse Events	AEs of CTCAE G3, Causally Related to AZD2014	5 Participants
100 mg QD Continuous	Adverse Events	Any AE, Causally Related to Fulvestrant Only	3 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	AEs of CTCAE G3, Causally Related to AZD2014	16 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any AE of CTCAE Grade ≥ 3 (G3)	24 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any AE of CTCAE G3, Related to Fulvestrant Only	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any AE, Causally Related to Fulvestrant Only	12 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any SAE, Causally Related to AZD2014	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any AE Leading to Discontinuation of AZD2014	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	AE with Outcome of Death, Related to AZD2014	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any Adverse Event with Outcome of Death	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any SAE Leading to Discontinuation of AZD2014	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any AE, Causally Related to AZD2014	35 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any Serious Adverse Event (SAE)	7 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	AE Outcome of Death, Related to Fulvestrant Only	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any SAE, Causally Related to Fulvestrant Only	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any Adverse Event (AE)	37 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	AE Outcome of Death, Related to Fulvestrant Only	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any Adverse Event (AE)	4 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any AE, Causally Related to AZD2014	4 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any AE, Causally Related to Fulvestrant Only	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any AE of CTCAE Grade ≥ 3 (G3)	3 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	AEs of CTCAE G3, Causally Related to AZD2014	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any AE of CTCAE G3, Related to Fulvestrant Only	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any Adverse Event with Outcome of Death	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	AE with Outcome of Death, Related to AZD2014	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any Serious Adverse Event (SAE)	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any SAE, Causally Related to AZD2014	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any SAE, Causally Related to Fulvestrant Only	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any AE Leading to Discontinuation of AZD2014	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any SAE Leading to Discontinuation of AZD2014	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any AE, Causally Related to AZD2014	8 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any Serious Adverse Event (SAE)	3 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any AE of CTCAE G3, Related to Fulvestrant Only	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	AE Outcome of Death, Related to Fulvestrant Only	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	AEs of CTCAE G3, Causally Related to AZD2014	6 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	AE with Outcome of Death, Related to AZD2014	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any AE Leading to Discontinuation of AZD2014	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any Adverse Event (AE)	8 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any SAE, Causally Related to Fulvestrant Only	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any SAE, Causally Related to AZD2014	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any SAE Leading to Discontinuation of AZD2014	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any AE of CTCAE Grade ≥ 3 (G3)	6 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any Adverse Event with Outcome of Death	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events	Any AE, Causally Related to Fulvestrant Only	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any AE, Causally Related to Fulvestrant Only	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any Adverse Event (AE)	5 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any AE Leading to Discontinuation of AZD2014	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any AE of CTCAE G3, Related to Fulvestrant Only	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any AE, Causally Related to AZD2014	5 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	AE Outcome of Death, Related to Fulvestrant Only	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	AE with Outcome of Death, Related to AZD2014	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any SAE, Causally Related to AZD2014	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any Serious Adverse Event (SAE)	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	AEs of CTCAE G3, Causally Related to AZD2014	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any AE of CTCAE Grade ≥ 3 (G3)	3 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any SAE Leading to Discontinuation of AZD2014	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any SAE, Causally Related to Fulvestrant Only	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events	Any Adverse Event with Outcome of Death	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	AE with Outcome of Death, Related to AZD2014	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	Any Adverse Event with Outcome of Death	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	Any Serious Adverse Event (SAE)	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	Any AE of CTCAE G3, Related to Fulvestrant Only	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	Any SAE, Causally Related to AZD2014	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	AEs of CTCAE G3, Causally Related to AZD2014	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	Any AE of CTCAE Grade ≥ 3 (G3)	1 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	Any SAE, Causally Related to Fulvestrant Only	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	Any AE, Causally Related to Fulvestrant Only	1 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	Any AE, Causally Related to AZD2014	2 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	Any AE Leading to Discontinuation of AZD2014	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	Any Adverse Event (AE)	2 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	AE Outcome of Death, Related to Fulvestrant Only	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events	Any SAE Leading to Discontinuation of AZD2014	0 Participants

Primary

Adverse Events Leading to Dose Reduction of AZD2014

Time frame: Up to 28 Days

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

Arm	Measure	Value (NUMBER)
35 mg BID Continuous	Adverse Events Leading to Dose Reduction of AZD2014	1 Participants
50 mg BID Continuous	Adverse Events Leading to Dose Reduction of AZD2014	7 Participants
75 mg QD Continuous	Adverse Events Leading to Dose Reduction of AZD2014	4 Participants
100 mg QD Continuous	Adverse Events Leading to Dose Reduction of AZD2014	6 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events Leading to Dose Reduction of AZD2014	12 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events Leading to Dose Reduction of AZD2014	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Adverse Events Leading to Dose Reduction of AZD2014	4 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Adverse Events Leading to Dose Reduction of AZD2014	3 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Adverse Events Leading to Dose Reduction of AZD2014	2 Participants

Primary

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

Time frame: 5 Days

Arm	Measure	Value (MEAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5080 h*ng/mL	Standard Deviation 1985
75 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	9723 h*ng/mL	Standard Deviation 6408
100 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	12590 h*ng/mL	Standard Deviation 4900

Primary

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant

Time frame: 15 Days

Arm	Measure	Value (MEAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant	13760 h*ng/mL	Standard Deviation 5737
75 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant	26570 h*ng/mL	Standard Deviation 8600
100 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant	16150 h*ng/mL	Standard Deviation 5591

Primary

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant

Time frame: 15 Days

Arm	Measure	Value (MEAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant	11810 h*ng/mL	Standard Deviation 7107
75 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant	13510 h*ng/mL	Standard Deviation 8937
100 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant	15580 h*ng/mL	Standard Deviation 6024

Primary

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

Time frame: 5 Days

Arm	Measure	Value (MEAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	6006 h*ng/mL	Standard Deviation 2838
75 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	11650 h*ng/mL	Standard Deviation 8685
100 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	15790 h*ng/mL	Standard Deviation 7286

Primary

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

Time frame: 5 Days

Arm	Measure	Value (MEAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	6392 h*ng/mL	Standard Deviation 3350
75 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	12360 h*ng/mL	Standard Deviation 9950
100 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	17360 h*ng/mL	Standard Deviation 9479

Primary

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

Time frame: 5 Days

Arm	Measure	Value (MEAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5832 h*ng/mL	Standard Deviation 2926
75 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	11500 h*ng/mL	Standard Deviation 8761
100 mg QD Continuous	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	15660 h*ng/mL	Standard Deviation 7345

Primary

AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

Time frame: 5 Days

Arm	Measure	Value (MEAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	1023 ng/mL	Standard Deviation 339.4
75 mg QD Continuous	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	1895 ng/mL	Standard Deviation 965.6
100 mg QD Continuous	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	2166 ng/mL	Standard Deviation 964.3

Primary

AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant

Time frame: 15 Days

Arm	Measure	Value (MEAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	1933 ng/mL	Standard Deviation 793.9
75 mg QD Continuous	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	4238 ng/mL	Standard Deviation 1440
100 mg QD Continuous	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	2454 ng/mL	Standard Deviation 838.4

Primary

AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant

Time frame: 22 Days

Arm	Measure	Value (MEAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	1785 ng/mL	Standard Deviation 866
75 mg QD Continuous	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	2409 ng/mL	Standard Deviation 1305
100 mg QD Continuous	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	2327 ng/mL	Standard Deviation 1257

Primary

Body Temperature

Time frame: 28 Days

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

Arm	Measure	Group	Value (MEAN)	Dispersion
35 mg BID Continuous	Body Temperature	Cycle 1, Day 15	36.48 °C	Standard Deviation 0.313
35 mg BID Continuous	Body Temperature	Cycle 1, Day 22	36.13 °C	Standard Deviation 0.403
35 mg BID Continuous	Body Temperature	Baseline	36.35 °C	Standard Deviation 0.327
35 mg BID Continuous	Body Temperature	Cycle 1, Day 8	36.33 °C	Standard Deviation 0.308
35 mg BID Continuous	Body Temperature	Cycle 2, Day 1	36.25 °C	Standard Deviation 0.315
35 mg BID Continuous	Body Temperature	Cycle 1, Day 1	36.33 °C	Standard Deviation 0.189
50 mg BID Continuous	Body Temperature	Cycle 1, Day 1	36.57 °C	Standard Deviation 0.465
50 mg BID Continuous	Body Temperature	Cycle 2, Day 1	36.55 °C	Standard Deviation 0.238
50 mg BID Continuous	Body Temperature	Baseline	36.44 °C	Standard Deviation 0.399
50 mg BID Continuous	Body Temperature	Cycle 1, Day 22	36.38 °C	Standard Deviation 0.36
50 mg BID Continuous	Body Temperature	Cycle 1, Day 15	36.74 °C	Standard Deviation 0.323
50 mg BID Continuous	Body Temperature	Cycle 1, Day 8	36.42 °C	Standard Deviation 0.217
75 mg QD Continuous	Body Temperature	Cycle 1, Day 15	36.45 °C	Standard Deviation 0.333
75 mg QD Continuous	Body Temperature	Cycle 2, Day 1	36.57 °C	Standard Deviation 0.312
75 mg QD Continuous	Body Temperature	Cycle 1, Day 1	36.34 °C	Standard Deviation 0.318
75 mg QD Continuous	Body Temperature	Cycle 1, Day 8	36.59 °C	Standard Deviation 0.493
75 mg QD Continuous	Body Temperature	Baseline	36.46 °C	Standard Deviation 0.303
75 mg QD Continuous	Body Temperature	Cycle 1, Day 22	36.38 °C	Standard Deviation 0.414
100 mg QD Continuous	Body Temperature	Baseline	36.48 °C	Standard Deviation 0.297
100 mg QD Continuous	Body Temperature	Cycle 1, Day 22	36.26 °C	Standard Deviation 0.45
100 mg QD Continuous	Body Temperature	Cycle 1, Day 15	36.35 °C	Standard Deviation 0.299
100 mg QD Continuous	Body Temperature	Cycle 1, Day 8	36.35 °C	Standard Deviation 0.372
100 mg QD Continuous	Body Temperature	Cycle 1, Day 1	36.46 °C	Standard Deviation 0.306
100 mg QD Continuous	Body Temperature	Cycle 2, Day 1	36.54 °C	Standard Deviation 0.444
125 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Cycle 1, Day 22	36.54 °C	Standard Deviation 0.55
125 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Baseline	36.57 °C	Standard Deviation 0.32
125 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Cycle 1, Day 8	36.51 °C	Standard Deviation 0.37
125 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Cycle 1, Day 15	36.50 °C	Standard Deviation 0.4
125 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Cycle 2, Day 1	36.56 °C	Standard Deviation 0.292
125 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Cycle 1, Day 1	36.57 °C	Standard Deviation 0.32
125 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Cycle 1, Day 22	36.65 °C	Standard Deviation 0.465
125 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Baseline	36.60 °C	Standard Deviation 0.183
125 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Cycle 1, Day 1	36.60 °C	Standard Deviation 0.183
125 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Cycle 1, Day 8	36.25 °C	Standard Deviation 0.129
125 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Cycle 1, Day 15	36.30 °C	Standard Deviation 0.216
125 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Cycle 2, Day 1	36.90 °C	Standard Deviation 0.294
170 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Cycle 1, Day 8	36.36 °C	Standard Deviation 0.276
170 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Baseline	36.39 °C	Standard Deviation 0.482
170 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Cycle 1, Day 1	36.39 °C	Standard Deviation 0.482
170 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Cycle 2, Day 1	36.50 °C	Standard Deviation 0.456
170 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Cycle 1, Day 22	36.66 °C	Standard Deviation 0.341
170 mg BID Intermittent Days 1 and 2 (Fasted)	Body Temperature	Cycle 1, Day 15	36.77 °C	Standard Deviation 0.489
170 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Cycle 1, Day 1	36.40 °C	Standard Deviation 0.394
170 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Cycle 1, Day 22	36.88 °C	Standard Deviation 0.319
170 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Baseline	36.40 °C	Standard Deviation 0.394
170 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Cycle 1, Day 8	36.88 °C	Standard Deviation 0.359
170 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Cycle 2, Day 1	36.54 °C	Standard Deviation 0.152
170 mg BID Intermittent Days 1 and 2 (Fed)	Body Temperature	Cycle 1, Day 15	36.42 °C	Standard Deviation 0.13
125 mg BID Intermittent Days 1 and 4 (Fasted)	Body Temperature	Cycle 1, Day 15	NA °C	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Body Temperature	Cycle 1, Day 8	NA °C	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Body Temperature	Cycle 1, Day 22	NA °C	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Body Temperature	Cycle 1, Day 1	NA °C	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Body Temperature	Baseline	NA °C	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Body Temperature	Cycle 2, Day 1	NA °C	—

Primary

Clinically Important Changes in Clinical Chemistry Parameters

Time frame: Up to 12 Months

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

Arm	Measure	Group	Value (NUMBER)
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium ≥ 2 CTCAE Grades	1 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Non Fasting Glucose to CTCAE Gr.3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate ≥ 2 CTCAE Grades	1 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin ≥ 2 CTCAE Grades	1 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in NonFasting Glucose ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose ≥ 2 CTCAE Grades	1 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in NonFasting Glucose ≥ 2 CTCAE Grades	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Non Fasting Glucose to CTCAE Gr.3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium ≥ 2 CTCAE Grades	1 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT ≥ 2 CTCAE Grades	1 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin ≥ 2 CTCAE Grades	1 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine ≥ 2 CTCAE Grades	1 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium ≥ 2 CTCAE Grades	1 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium ≥ 2 CTCAE Grades	1 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase ≥ 2 CTCAE Grades	2 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase to CTCAE Grade 3 or 4	1 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium to CTCAE Grade 3 or 4	1 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium ≥ 2 CTCAE Grades	3 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose ≥ 2 CTCAE Grades	1 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate to CTCAE Grade 3 or 4	1 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin ≥ 2 CTCAE Grades	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate ≥ 2 CTCAE Grades	1 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST ≥ 2 CTCAE Grades	2 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate ≥ 2 CTCAE Grades	2 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate ≥ 2 CTCAE Grades	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase to CTCAE Grade 3 or 4	1 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate to CTCAE Grade 3 or 4	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium ≥ 2 CTCAE Grades	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium to CTCAE Grade 3 or 4	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium to CTCAE Grade 3 or 4	1 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in NonFasting Glucose ≥ 2 CTCAE Grades	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Non Fasting Glucose to CTCAE Gr.3 or 4	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT ≥ 2 CTCAE Grades	3 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT to CTCAE Grade 3 or 4	2 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST ≥ 2 CTCAE Grades	3 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST to CTCAE Grade 3 or 4	5 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase ≥ 2 CTCAE Grades	1 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin ≥ 2 CTCAE Grades	2 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin to CTCAE Grade 3 or 4	1 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin ≥ 2 CTCAE Grades	1 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin to CTCAE Grade 3 or 4	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine ≥ 2 CTCAE Grades	1 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine to CTCAE Grade 3 or 4	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate ≥ 2 CTCAE Grades	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate to CTCAE Grade 3 or 4	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium ≥ 2 CTCAE Grades	1 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium to CTCAE Grade 3 or 4	1 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium ≥ 2 CTCAE Grades	2 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium ≥ 2 CTCAE Grades	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium to CTCAE Grade 3 or 4	0 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose ≥ 2 CTCAE Grades	1 Participants
75 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in NonFasting Glucose ≥ 2 CTCAE Grades	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose ≥ 2 CTCAE Grades	1 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT to CTCAE Grade 3 or 4	1 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase ≥ 2 CTCAE Grades	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Non Fasting Glucose to CTCAE Gr.3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium ≥ 2 CTCAE Grades	3 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium ≥ 2 CTCAE Grades	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium to CTCAE Grade 3 or 4	2 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT ≥ 2 CTCAE Grades	3 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium ≥ 2 CTCAE Grades	5 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin ≥ 2 CTCAE Grades	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium ≥ 2 CTCAE Grades	2 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST to CTCAE Grade 3 or 4	2 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium to CTCAE Grade 3 or 4	5 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin ≥ 2 CTCAE Grades	2 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium to CTCAE Grade 3 or 4	2 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate ≥ 2 CTCAE Grades	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST ≥ 2 CTCAE Grades	2 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine ≥ 2 CTCAE Grades	1 Participants
100 mg QD Continuous	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate ≥ 2 CTCAE Grades	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate ≥ 2 CTCAE Grades	15 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST ≥ 2 CTCAE Grades	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Non Fasting Glucose to CTCAE Gr.3 or 4	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose to CTCAE Grade 3 or 4	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in NonFasting Glucose ≥ 2 CTCAE Grades	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium to CTCAE Grade 3 or 4	5 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin ≥ 2 CTCAE Grades	6 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate to CTCAE Grade 3 or 4	7 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose ≥ 2 CTCAE Grades	7 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium ≥ 2 CTCAE Grades	6 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium ≥ 2 CTCAE Grades	5 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin ≥ 2 CTCAE Grades	3 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST to CTCAE Grade 3 or 4	3 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in NonFasting Glucose ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Non Fasting Glucose to CTCAE Gr.3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose ≥ 2 CTCAE Grades	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose ≥ 2 CTCAE Grades	4 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase to CTCAE Grade 3 or 4	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium to CTCAE Grade 3 or 4	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium to CTCAE Grade 3 or 4	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase ≥ 2 CTCAE Grades	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Non Fasting Glucose to CTCAE Gr.3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin ≥ 2 CTCAE Grades	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium ≥ 2 CTCAE Grades	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in NonFasting Glucose ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium ≥ 2 CTCAE Grades	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin ≥ 2 CTCAE Grades	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate ≥ 2 CTCAE Grades	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Non Fasting Glucose to CTCAE Gr.3 or 4	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin ≥ 2 CTCAE Grades	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate to CTCAE Grade 3 or 4	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose to CTCAE Grade 3 or 4	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in NonFasting Glucose ≥ 2 CTCAE Grades	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium ≥ 2 CTCAE Grades	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin ≥ 2 CTCAE Grades	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium to CTCAE Grade 3 or 4	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate ≥ 2 CTCAE Grades	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Sodium ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in NonFasting Glucose ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in AST to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Albumin ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Non Fasting Glucose to CTCAE Gr.3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Bilirubin to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Calcium to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Potassium ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in ALT to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Fasting Glucose ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Phosphate to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Magnesium ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Alk Phosphatase to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Creatinine ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Clinical Chemistry Parameters	Change in Urate to CTCAE Grade 3 or 4	0 Participants

Primary

Clinically Important Changes in Haematology Parameters

Time frame: Up to 12 Months

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

Arm	Measure	Group	Value (NUMBER)
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Leukocytes ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Platelets ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Neutrophils to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Leukocytes to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Neutrophils ≥ 2 CTCAE Grades	1 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes ≥ 2 CTCAE Grades	2 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in aPTT ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Platelets to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in INR to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in INR ≥ 2 CTCAE Grades	0 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in aPTT to CTCAE Grade 3 or 4	0 Participants
35 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in aPTT to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin ≥ 2 CTCAE Grades	0 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in INR to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Platelets to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in aPTT ≥ 2 CTCAE Grades	1 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Leukocytes to CTCAE Grade 3 or 4	1 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Platelets ≥ 2 CTCAE Grades	0 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin to CTCAE Grade 3 or 4	0 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes to CTCAE Grade 3 or 4	3 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Leukocytes ≥ 2 CTCAE Grades	4 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Neutrophils to CTCAE Grade 3 or 4	1 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes ≥ 2 CTCAE Grades	6 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in INR ≥ 2 CTCAE Grades	0 Participants
50 mg BID Continuous	Clinically Important Changes in Haematology Parameters	Change in Neutrophils ≥ 2 CTCAE Grades	4 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Neutrophils ≥ 2 CTCAE Grades	1 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin to CTCAE Grade 3 or 4	0 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Platelets ≥ 2 CTCAE Grades	2 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Neutrophils to CTCAE Grade 3 or 4	1 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in INR ≥ 2 CTCAE Grades	0 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in aPTT to CTCAE Grade 3 or 4	0 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin ≥ 2 CTCAE Grades	0 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Leukocytes ≥ 2 CTCAE Grades	2 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Leukocytes to CTCAE Grade 3 or 4	1 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in INR to CTCAE Grade 3 or 4	0 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in aPTT ≥ 2 CTCAE Grades	0 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes ≥ 2 CTCAE Grades	8 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes to CTCAE Grade 3 or 4	3 Participants
75 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Platelets to CTCAE Grade 3 or 4	1 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Platelets ≥ 2 CTCAE Grades	0 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Leukocytes ≥ 2 CTCAE Grades	1 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Neutrophils to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes ≥ 2 CTCAE Grades	5 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in INR ≥ 2 CTCAE Grades	0 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin ≥ 2 CTCAE Grades	0 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Platelets to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Neutrophils ≥ 2 CTCAE Grades	3 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in aPTT to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in aPTT ≥ 2 CTCAE Grades	0 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in INR to CTCAE Grade 3 or 4	0 Participants
100 mg QD Continuous	Clinically Important Changes in Haematology Parameters	Change in Leukocytes to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Leukocytes ≥ 2 CTCAE Grades	9 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Leukocytes to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Neutrophils to CTCAE Grade 3 or 4	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in INR ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in INR to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in aPTT ≥ 2 CTCAE Grades	3 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Neutrophils ≥ 2 CTCAE Grades	12 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Platelets ≥ 2 CTCAE Grades	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in aPTT to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes ≥ 2 CTCAE Grades	10 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes to CTCAE Grade 3 or 4	7 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Platelets to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Platelets to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in aPTT ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Leukocytes ≥ 2 CTCAE Grades	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Leukocytes to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Neutrophils ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Neutrophils to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Platelets ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in aPTT to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in INR ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in INR to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in aPTT ≥ 2 CTCAE Grades	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in aPTT to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Leukocytes to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in INR to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Leukocytes ≥ 2 CTCAE Grades	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Neutrophils to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes to CTCAE Grade 3 or 4	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in INR ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Platelets ≥ 2 CTCAE Grades	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes ≥ 2 CTCAE Grades	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Platelets to CTCAE Grade 3 or 4	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Neutrophils ≥ 2 CTCAE Grades	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Platelets ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes to CTCAE Grade 3 or 4	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes ≥ 2 CTCAE Grades	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Platelets to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Leukocytes to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Leukocytes ≥ 2 CTCAE Grades	3 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in aPTT to CTCAE Grade 3 or 4	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in aPTT ≥ 2 CTCAE Grades	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in INR to CTCAE Grade 3 or 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in INR ≥ 2 CTCAE Grades	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Neutrophils ≥ 2 CTCAE Grades	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinically Important Changes in Haematology Parameters	Change in Neutrophils to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Platelets ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Neutrophils to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes ≥ 2 CTCAE Grades	1 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Neutrophils ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in INR ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Lymphocytes to CTCAE Grade 3 or 4	1 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Leukocytes ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Leukocytes to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Hemoglobin ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in aPTT to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in aPTT ≥ 2 CTCAE Grades	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in INR to CTCAE Grade 3 or 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinically Important Changes in Haematology Parameters	Change in Platelets to CTCAE Grade 3 or 4	0 Participants

Primary

Heart Rate

Time frame: 28 Days

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

Arm	Measure	Group	Value (MEAN)	Dispersion
35 mg BID Continuous	Heart Rate	Cycle 1, Day 8	80.8 beats/min	Standard Deviation 11.39
35 mg BID Continuous	Heart Rate	Cycle 2, Day 1	83.5 beats/min	Standard Deviation 11.81
35 mg BID Continuous	Heart Rate	Cycle 1, Day 1	87.3 beats/min	Standard Deviation 4.92
35 mg BID Continuous	Heart Rate	Baseline	87.5 beats/min	Standard Deviation 11.36
35 mg BID Continuous	Heart Rate	Cycle 1, Day 22	82.4 beats/min	Standard Deviation 13.58
35 mg BID Continuous	Heart Rate	Cycle 1, Day 15	80.2 beats/min	Standard Deviation 9.97
50 mg BID Continuous	Heart Rate	Cycle 2, Day 1	89.7 beats/min	Standard Deviation 11.63
50 mg BID Continuous	Heart Rate	Cycle 1, Day 22	87.8 beats/min	Standard Deviation 16.95
50 mg BID Continuous	Heart Rate	Cycle 1, Day 1	77.7 beats/min	Standard Deviation 14.28
50 mg BID Continuous	Heart Rate	Cycle 1, Day 15	89.3 beats/min	Standard Deviation 16.83
50 mg BID Continuous	Heart Rate	Cycle 1, Day 8	81.2 beats/min	Standard Deviation 15.93
50 mg BID Continuous	Heart Rate	Baseline	84.5 beats/min	Standard Deviation 13.31
75 mg QD Continuous	Heart Rate	Cycle 1, Day 8	85.4 beats/min	Standard Deviation 19.97
75 mg QD Continuous	Heart Rate	Cycle 1, Day 22	85.3 beats/min	Standard Deviation 20.23
75 mg QD Continuous	Heart Rate	Cycle 2, Day 1	84.0 beats/min	Standard Deviation 16.39
75 mg QD Continuous	Heart Rate	Cycle 1, Day 15	86.7 beats/min	Standard Deviation 18.48
75 mg QD Continuous	Heart Rate	Baseline	82.7 beats/min	Standard Deviation 14.14
75 mg QD Continuous	Heart Rate	Cycle 1, Day 1	87.3 beats/min	Standard Deviation 19.53
100 mg QD Continuous	Heart Rate	Cycle 1, Day 1	86.8 beats/min	Standard Deviation 12.9
100 mg QD Continuous	Heart Rate	Baseline	81.0 beats/min	Standard Deviation 13.11
100 mg QD Continuous	Heart Rate	Cycle 1, Day 8	92.6 beats/min	Standard Deviation 12.47
100 mg QD Continuous	Heart Rate	Cycle 1, Day 15	82.8 beats/min	Standard Deviation 8.6
100 mg QD Continuous	Heart Rate	Cycle 1, Day 22	86.1 beats/min	Standard Deviation 11.18
100 mg QD Continuous	Heart Rate	Cycle 2, Day 1	87.9 beats/min	Standard Deviation 12.45
125 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Baseline	83.5 beats/min	Standard Deviation 15.32
125 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Cycle 1, Day 22	84.6 beats/min	Standard Deviation 17.27
125 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Cycle 1, Day 8	84.4 beats/min	Standard Deviation 15.61
125 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Cycle 1, Day 15	81.3 beats/min	Standard Deviation 14.79
125 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Cycle 2, Day 1	85.7 beats/min	Standard Deviation 15.53
125 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Cycle 1, Day 1	83.5 beats/min	Standard Deviation 15.32
125 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Cycle 1, Day 15	83.3 beats/min	Standard Deviation 15.33
125 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Baseline	73.5 beats/min	Standard Deviation 10.75
125 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Cycle 1, Day 22	77.8 beats/min	Standard Deviation 7.8
125 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Cycle 2, Day 1	78.0 beats/min	Standard Deviation 15.75
125 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Cycle 1, Day 8	71.5 beats/min	Standard Deviation 6.61
125 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Cycle 1, Day 1	73.5 beats/min	Standard Deviation 10.75
170 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Cycle 1, Day 8	79.4 beats/min	Standard Deviation 15.78
170 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Cycle 1, Day 1	86.1 beats/min	Standard Deviation 21.4
170 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Cycle 2, Day 1	83.0 beats/min	Standard Deviation 13.94
170 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Cycle 1, Day 15	82.5 beats/min	Standard Deviation 17.65
170 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Cycle 1, Day 22	87.4 beats/min	Standard Deviation 25.97
170 mg BID Intermittent Days 1 and 2 (Fasted)	Heart Rate	Baseline	86.1 beats/min	Standard Deviation 21.4
170 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Cycle 1, Day 22	88.8 beats/min	Standard Deviation 11.43
170 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Cycle 1, Day 15	77.4 beats/min	Standard Deviation 7.92
170 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Cycle 1, Day 8	75.5 beats/min	Standard Deviation 12.01
170 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Cycle 1, Day 1	79.6 beats/min	Standard Deviation 5.32
170 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Cycle 2, Day 1	85.0 beats/min	Standard Deviation 12.68
170 mg BID Intermittent Days 1 and 2 (Fed)	Heart Rate	Baseline	79.6 beats/min	Standard Deviation 5.32
125 mg BID Intermittent Days 1 and 4 (Fasted)	Heart Rate	Cycle 2, Day 1	NA beats/min	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Heart Rate	Cycle 1, Day 22	NA beats/min	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Heart Rate	Baseline	NA beats/min	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Heart Rate	Cycle 1, Day 15	NA beats/min	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Heart Rate	Cycle 1, Day 8	NA beats/min	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Heart Rate	Cycle 1, Day 1	NA beats/min	—

Primary

Left Ventricular Ejection Fraction

Time frame: 24 hours

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

Primary

Oxygen Saturation

Time frame: 28 Days

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

Arm	Measure	Group	Value (MEAN)	Dispersion
35 mg BID Continuous	Oxygen Saturation	Cycle 1, Day 8	98.3 % Arterial Oxygen Saturation	Standard Deviation 1.21
35 mg BID Continuous	Oxygen Saturation	Cycle 1, Day 22	96.8 % Arterial Oxygen Saturation	Standard Deviation 1.72
35 mg BID Continuous	Oxygen Saturation	Cycle 1, Day 15	97.7 % Arterial Oxygen Saturation	Standard Deviation 0.82
35 mg BID Continuous	Oxygen Saturation	Baseline	97.0 % Arterial Oxygen Saturation	Standard Deviation 0.89
35 mg BID Continuous	Oxygen Saturation	Cycle 1, Day 1	97.5 % Arterial Oxygen Saturation	Standard Deviation 1
35 mg BID Continuous	Oxygen Saturation	Cycle 2, Day 1	97.5 % Arterial Oxygen Saturation	Standard Deviation 0.55
50 mg BID Continuous	Oxygen Saturation	Cycle 1, Day 22	97.3 % Arterial Oxygen Saturation	Standard Deviation 1.82
50 mg BID Continuous	Oxygen Saturation	Cycle 1, Day 1	97.7 % Arterial Oxygen Saturation	Standard Deviation 1.9
50 mg BID Continuous	Oxygen Saturation	Cycle 1, Day 15	96.5 % Arterial Oxygen Saturation	Standard Deviation 1.94
50 mg BID Continuous	Oxygen Saturation	Cycle 1, Day 8	97.5 % Arterial Oxygen Saturation	Standard Deviation 1.98
50 mg BID Continuous	Oxygen Saturation	Cycle 2, Day 1	97.3 % Arterial Oxygen Saturation	Standard Deviation 2.09
50 mg BID Continuous	Oxygen Saturation	Baseline	97.2 % Arterial Oxygen Saturation	Standard Deviation 1.59
75 mg QD Continuous	Oxygen Saturation	Cycle 1, Day 1	97.4 % Arterial Oxygen Saturation	Standard Deviation 1.16
75 mg QD Continuous	Oxygen Saturation	Cycle 1, Day 22	96.8 % Arterial Oxygen Saturation	Standard Deviation 1.77
75 mg QD Continuous	Oxygen Saturation	Cycle 1, Day 15	97.3 % Arterial Oxygen Saturation	Standard Deviation 1.5
75 mg QD Continuous	Oxygen Saturation	Cycle 2, Day 1	96.9 % Arterial Oxygen Saturation	Standard Deviation 1.26
75 mg QD Continuous	Oxygen Saturation	Baseline	96.8 % Arterial Oxygen Saturation	Standard Deviation 1.85
75 mg QD Continuous	Oxygen Saturation	Cycle 1, Day 8	97.1 % Arterial Oxygen Saturation	Standard Deviation 1.66
100 mg QD Continuous	Oxygen Saturation	Baseline	96.7 % Arterial Oxygen Saturation	Standard Deviation 2.41
100 mg QD Continuous	Oxygen Saturation	Cycle 1, Day 8	97.1 % Arterial Oxygen Saturation	Standard Deviation 1.37
100 mg QD Continuous	Oxygen Saturation	Cycle 1, Day 1	96.9 % Arterial Oxygen Saturation	Standard Deviation 1.9
100 mg QD Continuous	Oxygen Saturation	Cycle 1, Day 22	97.6 % Arterial Oxygen Saturation	Standard Deviation 1.51
100 mg QD Continuous	Oxygen Saturation	Cycle 1, Day 15	97.1 % Arterial Oxygen Saturation	Standard Deviation 1.17
100 mg QD Continuous	Oxygen Saturation	Cycle 2, Day 1	97.3 % Arterial Oxygen Saturation	Standard Deviation 1.04
125 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Cycle 1, Day 22	98.1 % Arterial Oxygen Saturation	Standard Deviation 1.63
125 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Cycle 1, Day 15	98.0 % Arterial Oxygen Saturation	Standard Deviation 1.34
125 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Cycle 1, Day 1	97.8 % Arterial Oxygen Saturation	Standard Deviation 1.49
125 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Baseline	97.8 % Arterial Oxygen Saturation	Standard Deviation 1.49
125 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Cycle 1, Day 8	97.8 % Arterial Oxygen Saturation	Standard Deviation 1.7
125 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Cycle 2, Day 1	98.2 % Arterial Oxygen Saturation	Standard Deviation 1.39
125 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Cycle 1, Day 8	97.0 % Arterial Oxygen Saturation	Standard Deviation 2.16
125 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Cycle 2, Day 1	96.5 % Arterial Oxygen Saturation	Standard Deviation 2.52
125 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Cycle 1, Day 22	97.5 % Arterial Oxygen Saturation	Standard Deviation 3.11
125 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Baseline	97.0 % Arterial Oxygen Saturation	Standard Deviation 1.83
125 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Cycle 1, Day 1	97.0 % Arterial Oxygen Saturation	Standard Deviation 1.83
125 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Cycle 1, Day 15	97.0 % Arterial Oxygen Saturation	Standard Deviation 1.41
170 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Cycle 1, Day 8	97.7 % Arterial Oxygen Saturation	Standard Deviation 1.5
170 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Cycle 1, Day 15	97.0 % Arterial Oxygen Saturation	Standard Deviation 1.26
170 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Cycle 2, Day 1	96.2 % Arterial Oxygen Saturation	Standard Deviation 3.31
170 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Baseline	97.0 % Arterial Oxygen Saturation	Standard Deviation 0.93
170 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Cycle 1, Day 22	97.9 % Arterial Oxygen Saturation	Standard Deviation 1.57
170 mg BID Intermittent Days 1 and 2 (Fasted)	Oxygen Saturation	Cycle 1, Day 1	97.0 % Arterial Oxygen Saturation	Standard Deviation 0.93
170 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Cycle 1, Day 1	97.6 % Arterial Oxygen Saturation	Standard Deviation 1.14
170 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Baseline	97.6 % Arterial Oxygen Saturation	Standard Deviation 1.14
170 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Cycle 1, Day 8	98.3 % Arterial Oxygen Saturation	Standard Deviation 2.06
170 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Cycle 2, Day 1	97.0 % Arterial Oxygen Saturation	Standard Deviation 2.16
170 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Cycle 1, Day 22	98.0 % Arterial Oxygen Saturation	Standard Deviation 1.63
170 mg BID Intermittent Days 1 and 2 (Fed)	Oxygen Saturation	Cycle 1, Day 15	96.8 % Arterial Oxygen Saturation	Standard Deviation 1.48
125 mg BID Intermittent Days 1 and 4 (Fasted)	Oxygen Saturation	Cycle 1, Day 1	NA % Arterial Oxygen Saturation	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Oxygen Saturation	Cycle 2, Day 1	NA % Arterial Oxygen Saturation	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Oxygen Saturation	Cycle 1, Day 15	NA % Arterial Oxygen Saturation	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Oxygen Saturation	Baseline	NA % Arterial Oxygen Saturation	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Oxygen Saturation	Cycle 1, Day 8	NA % Arterial Oxygen Saturation	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Oxygen Saturation	Cycle 1, Day 22	NA % Arterial Oxygen Saturation	—

Primary

Post-Baseline Glucose Elevation

Time frame: 28 Days

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

Arm	Measure	Group	Value (NUMBER)
35 mg BID Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 3	0 Participants
35 mg BID Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 4	0 Participants
35 mg BID Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 1	2 Participants
35 mg BID Continuous	Post-Baseline Glucose Elevation	Participants with ≥ 1 post-baseline elevation	3 Participants
35 mg BID Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 2	1 Participants
50 mg BID Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 2	0 Participants
50 mg BID Continuous	Post-Baseline Glucose Elevation	Participants with ≥ 1 post-baseline elevation	6 Participants
50 mg BID Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 3	1 Participants
50 mg BID Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 1	5 Participants
50 mg BID Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 4	0 Participants
75 mg QD Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 4	0 Participants
75 mg QD Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 2	0 Participants
75 mg QD Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 3	2 Participants
75 mg QD Continuous	Post-Baseline Glucose Elevation	Participants with ≥ 1 post-baseline elevation	7 Participants
75 mg QD Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 1	5 Participants
100 mg QD Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 2	1 Participants
100 mg QD Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 3	1 Participants
100 mg QD Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 4	0 Participants
100 mg QD Continuous	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 1	3 Participants
100 mg QD Continuous	Post-Baseline Glucose Elevation	Participants with ≥ 1 post-baseline elevation	5 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 3	5 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 1	17 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Post-Baseline Glucose Elevation	Participants with ≥ 1 post-baseline elevation	29 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 2	7 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 1	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 3	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Post-Baseline Glucose Elevation	Participants with ≥ 1 post-baseline elevation	3 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 4	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 2	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 1	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 3	3 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 2	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Post-Baseline Glucose Elevation	Participants with ≥ 1 post-baseline elevation	6 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 1	4 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Post-Baseline Glucose Elevation	Participants with ≥ 1 post-baseline elevation	5 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 4	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 2	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 3	1 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 3	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 4	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 2	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Post-Baseline Glucose Elevation	Participants with ≥ 1 post-baseline elevation	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Post-Baseline Glucose Elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 1	0 Participants

Primary

QTcF Over 24 Hours

Time frame: 24 hours

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

Arm	Measure	Group	Value (MEAN)	Dispersion
35 mg BID Continuous	QTcF Over 24 Hours	0.5 Hours Postdose	431.84 msec	Standard Deviation 7.504
35 mg BID Continuous	QTcF Over 24 Hours	0.25 Hours Postdose	429.66 msec	Standard Deviation 5.707
35 mg BID Continuous	QTcF Over 24 Hours	12 Hours Postdose	427.74 msec	Standard Deviation 15.157
35 mg BID Continuous	QTcF Over 24 Hours	4 Hours Postdose	422.00 msec	Standard Deviation 10.583
35 mg BID Continuous	QTcF Over 24 Hours	6 Hours Postdose	421.50 msec	Standard Deviation 15.453
35 mg BID Continuous	QTcF Over 24 Hours	2 Hours Postdose	433.02 msec	Standard Deviation 11.921
35 mg BID Continuous	QTcF Over 24 Hours	8 Hours Postdose	424.86 msec	Standard Deviation 12.688
35 mg BID Continuous	QTcF Over 24 Hours	24 Hours Postdose	425.54 msec	Standard Deviation 10.519
35 mg BID Continuous	QTcF Over 24 Hours	1.5 Hours Postdose	431.82 msec	Standard Deviation 8.569
35 mg BID Continuous	QTcF Over 24 Hours	Baseline	423.12 msec	Standard Deviation 11.07
35 mg BID Continuous	QTcF Over 24 Hours	1 Hour Postdose	431.00 msec	Standard Deviation 10.149
50 mg BID Continuous	QTcF Over 24 Hours	Baseline	421.92 msec	Standard Deviation 22.715
50 mg BID Continuous	QTcF Over 24 Hours	24 Hours Postdose	421.45 msec	Standard Deviation 16.339
50 mg BID Continuous	QTcF Over 24 Hours	2 Hours Postdose	423.31 msec	Standard Deviation 22.678
50 mg BID Continuous	QTcF Over 24 Hours	1.5 Hours Postdose	425.15 msec	Standard Deviation 22.106
50 mg BID Continuous	QTcF Over 24 Hours	8 Hours Postdose	420.16 msec	Standard Deviation 20.437
50 mg BID Continuous	QTcF Over 24 Hours	1 Hour Postdose	422.21 msec	Standard Deviation 21.863
50 mg BID Continuous	QTcF Over 24 Hours	0.5 Hours Postdose	419.18 msec	Standard Deviation 21.362
50 mg BID Continuous	QTcF Over 24 Hours	0.25 Hours Postdose	420.13 msec	Standard Deviation 18.333
50 mg BID Continuous	QTcF Over 24 Hours	12 Hours Postdose	425.46 msec	Standard Deviation 21.533
50 mg BID Continuous	QTcF Over 24 Hours	4 Hours Postdose	419.97 msec	Standard Deviation 21.322
50 mg BID Continuous	QTcF Over 24 Hours	6 Hours Postdose	419.14 msec	Standard Deviation 21.269
75 mg QD Continuous	QTcF Over 24 Hours	1 Hour Postdose	416.08 msec	Standard Deviation 17.581
75 mg QD Continuous	QTcF Over 24 Hours	6 Hours Postdose	411.85 msec	Standard Deviation 13.387
75 mg QD Continuous	QTcF Over 24 Hours	24 Hours Postdose	409.33 msec	Standard Deviation 16.313
75 mg QD Continuous	QTcF Over 24 Hours	2 Hours Postdose	415.84 msec	Standard Deviation 17.508
75 mg QD Continuous	QTcF Over 24 Hours	4 Hours Postdose	411.18 msec	Standard Deviation 15.886
75 mg QD Continuous	QTcF Over 24 Hours	Baseline	412.78 msec	Standard Deviation 14.222
75 mg QD Continuous	QTcF Over 24 Hours	1.5 Hours Postdose	415.36 msec	Standard Deviation 16.394
75 mg QD Continuous	QTcF Over 24 Hours	0.25 Hours Postdose	413.04 msec	Standard Deviation 14.934
75 mg QD Continuous	QTcF Over 24 Hours	12 Hours Postdose	409.67 msec	Standard Deviation 19.176
75 mg QD Continuous	QTcF Over 24 Hours	0.5 Hours Postdose	415.08 msec	Standard Deviation 14.762
75 mg QD Continuous	QTcF Over 24 Hours	8 Hours Postdose	411.16 msec	Standard Deviation 15.587
100 mg QD Continuous	QTcF Over 24 Hours	12 Hours Postdose	414.59 msec	Standard Deviation 15.76
100 mg QD Continuous	QTcF Over 24 Hours	6 Hours Postdose	414.74 msec	Standard Deviation 16.413
100 mg QD Continuous	QTcF Over 24 Hours	8 Hours Postdose	413.56 msec	Standard Deviation 15.072
100 mg QD Continuous	QTcF Over 24 Hours	Baseline	415.95 msec	Standard Deviation 14.849
100 mg QD Continuous	QTcF Over 24 Hours	0.5 Hours Postdose	418.91 msec	Standard Deviation 14.437
100 mg QD Continuous	QTcF Over 24 Hours	1 Hour Postdose	416.20 msec	Standard Deviation 14.53
100 mg QD Continuous	QTcF Over 24 Hours	1.5 Hours Postdose	415.33 msec	Standard Deviation 15.02
100 mg QD Continuous	QTcF Over 24 Hours	2 Hours Postdose	414.01 msec	Standard Deviation 17.988
100 mg QD Continuous	QTcF Over 24 Hours	4 Hours Postdose	410.88 msec	Standard Deviation 13.815
100 mg QD Continuous	QTcF Over 24 Hours	0.25 Hours Postdose	418.44 msec	Standard Deviation 16.145
100 mg QD Continuous	QTcF Over 24 Hours	24 Hours Postdose	415.29 msec	Standard Deviation 16.968
125 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	6 Hours Postdose	412.80 msec	Standard Deviation 17.342
125 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	24 Hours Postdose	422.73 msec	Standard Deviation 17.9
125 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	2 Hours Postdose	414.99 msec	Standard Deviation 17.25
125 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	0.5 Hours Postdose	413.28 msec	Standard Deviation 19.715
125 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	0.25 Hours Postdose	NA msec	—
125 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	1 Hour Postdose	416.22 msec	Standard Deviation 19.738
125 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	8 Hours Postdose	414.17 msec	Standard Deviation 18.533
125 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	12 Hours Postdose	414.09 msec	Standard Deviation 18.188
125 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	1.5 Hours Postdose	417.10 msec	Standard Deviation 19.672
125 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	4 Hours Postdose	414.04 msec	Standard Deviation 17.351
125 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	Baseline	419.95 msec	Standard Deviation 20.502
125 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	Baseline	427.13 msec	Standard Deviation 32.995
125 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	6 Hours Postdose	417.00 msec	Standard Deviation 20.421
125 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	8 Hours Postdose	419.90 msec	Standard Deviation 22.274
125 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	2 Hours Postdose	424.00 msec	Standard Deviation 22.528
125 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	4 Hours Postdose	424.43 msec	Standard Deviation 17.832
125 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	24 Hours Postdose	426.77 msec	Standard Deviation 16.591
125 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	1.5 Hours Postdose	434.33 msec	Standard Deviation 14.199
125 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	1 Hour Postdose	427.77 msec	Standard Deviation 10.186
125 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	0.5 Hours Postdose	418.90 msec	Standard Deviation 14.897
125 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	0.25 Hours Postdose	NA msec	—
125 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	12 Hours Postdose	431.70 msec	Standard Deviation 16.896
170 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	24 Hours Postdose	NA msec	—
170 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	1 Hour Postdose	419.61 msec	Standard Deviation 16.514
170 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	1.5 Hours Postdose	420.43 msec	Standard Deviation 15.627
170 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	6 Hours Postdose	422.94 msec	Standard Deviation 18.577
170 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	2 Hours Postdose	418.60 msec	Standard Deviation 15.144
170 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	4 Hours Postdose	426.60 msec	Standard Deviation 16.724
170 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	8 Hours Postdose	416.80 msec	Standard Deviation 15.144
170 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	0.25 Hours Postdose	NA msec	—
170 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	12 Hours Postdose	420.66 msec	Standard Deviation 10.462
170 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	Baseline	424.84 msec	Standard Deviation 6.932
170 mg BID Intermittent Days 1 and 2 (Fasted)	QTcF Over 24 Hours	0.5 Hours Postdose	415.67 msec	Standard Deviation 16.874
170 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	6 Hours Postdose	418.34 msec	Standard Deviation 13.781
170 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	24 Hours Postdose	NA msec	—
170 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	12 Hours Postdose	432.46 msec	Standard Deviation 16.503
170 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	0.25 Hours Postdose	NA msec	—
170 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	1 Hour Postdose	421.20 msec	Standard Deviation 21.336
170 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	2 Hours Postdose	422.94 msec	Standard Deviation 18.036
170 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	0.5 Hours Postdose	420.06 msec	Standard Deviation 18.388
170 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	8 Hours Postdose	425.54 msec	Standard Deviation 12.246
170 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	4 Hours Postdose	422.40 msec	Standard Deviation 10.397
170 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	Baseline	435.26 msec	Standard Deviation 7.971
170 mg BID Intermittent Days 1 and 2 (Fed)	QTcF Over 24 Hours	1.5 Hours Postdose	427.48 msec	Standard Deviation 20.863
125 mg BID Intermittent Days 1 and 4 (Fasted)	QTcF Over 24 Hours	1.5 Hours Postdose	NA msec	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	QTcF Over 24 Hours	0.5 Hours Postdose	NA msec	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	QTcF Over 24 Hours	8 Hours Postdose	NA msec	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	QTcF Over 24 Hours	0.25 Hours Postdose	NA msec	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	QTcF Over 24 Hours	6 Hours Postdose	NA msec	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	QTcF Over 24 Hours	1 Hour Postdose	NA msec	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	QTcF Over 24 Hours	24 Hours Postdose	NA msec	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	QTcF Over 24 Hours	12 Hours Postdose	NA msec	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	QTcF Over 24 Hours	Baseline	NA msec	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	QTcF Over 24 Hours	2 Hours Postdose	NA msec	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	QTcF Over 24 Hours	4 Hours Postdose	NA msec	—

Primary

Respiratory Rate

Time frame: 28 Days

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

Arm	Measure	Group	Value (MEAN)	Dispersion
35 mg BID Continuous	Respiratory Rate	Cycle 1, Day 8	17.3 breaths/min	Standard Deviation 1.63
35 mg BID Continuous	Respiratory Rate	Cycle 2, Day 1	17.3 breaths/min	Standard Deviation 1.63
35 mg BID Continuous	Respiratory Rate	Cycle 1, Day 1	16.0 breaths/min	Standard Deviation 1.63
35 mg BID Continuous	Respiratory Rate	Baseline	18.3 breaths/min	Standard Deviation 2.66
35 mg BID Continuous	Respiratory Rate	Cycle 1, Day 22	17.3 breaths/min	Standard Deviation 2.07
35 mg BID Continuous	Respiratory Rate	Cycle 1, Day 15	17.2 breaths/min	Standard Deviation 0.98
50 mg BID Continuous	Respiratory Rate	Cycle 2, Day 1	17.6 breaths/min	Standard Deviation 1.16
50 mg BID Continuous	Respiratory Rate	Cycle 1, Day 22	17.8 breaths/min	Standard Deviation 1.03
50 mg BID Continuous	Respiratory Rate	Cycle 1, Day 1	16.6 breaths/min	Standard Deviation 1.43
50 mg BID Continuous	Respiratory Rate	Cycle 1, Day 15	17.1 breaths/min	Standard Deviation 1.38
50 mg BID Continuous	Respiratory Rate	Cycle 1, Day 8	16.4 breaths/min	Standard Deviation 1.89
50 mg BID Continuous	Respiratory Rate	Baseline	17.5 breaths/min	Standard Deviation 1.85
75 mg QD Continuous	Respiratory Rate	Cycle 1, Day 8	17.6 breaths/min	Standard Deviation 1.34
75 mg QD Continuous	Respiratory Rate	Cycle 1, Day 22	18.0 breaths/min	Standard Deviation 1.15
75 mg QD Continuous	Respiratory Rate	Cycle 2, Day 1	17.8 breaths/min	Standard Deviation 0.99
75 mg QD Continuous	Respiratory Rate	Cycle 1, Day 15	18.5 breaths/min	Standard Deviation 1.2
75 mg QD Continuous	Respiratory Rate	Baseline	18.3 breaths/min	Standard Deviation 1.33
75 mg QD Continuous	Respiratory Rate	Cycle 1, Day 1	17.7 breaths/min	Standard Deviation 1.33
100 mg QD Continuous	Respiratory Rate	Cycle 1, Day 1	17.3 breaths/min	Standard Deviation 1.34
100 mg QD Continuous	Respiratory Rate	Baseline	17.8 breaths/min	Standard Deviation 2.39
100 mg QD Continuous	Respiratory Rate	Cycle 1, Day 8	17.5 breaths/min	Standard Deviation 0.85
100 mg QD Continuous	Respiratory Rate	Cycle 1, Day 15	17.9 breaths/min	Standard Deviation 1.66
100 mg QD Continuous	Respiratory Rate	Cycle 1, Day 22	17.1 breaths/min	Standard Deviation 1.07
100 mg QD Continuous	Respiratory Rate	Cycle 2, Day 1	18.3 breaths/min	Standard Deviation 1.28
125 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Baseline	17.5 breaths/min	Standard Deviation 0.96
125 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Cycle 1, Day 22	17.6 breaths/min	Standard Deviation 1.54
125 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Cycle 1, Day 8	17.2 breaths/min	Standard Deviation 1.47
125 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Cycle 1, Day 15	17.6 breaths/min	Standard Deviation 1.03
125 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Cycle 2, Day 1	17.3 breaths/min	Standard Deviation 2.11
125 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Cycle 1, Day 1	17.5 breaths/min	Standard Deviation 0.96
125 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Cycle 1, Day 15	17.0 breaths/min	Standard Deviation 0.82
125 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Baseline	17.5 breaths/min	Standard Deviation 0.58
125 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Cycle 1, Day 22	17.8 breaths/min	Standard Deviation 1.26
125 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Cycle 2, Day 1	17.8 breaths/min	Standard Deviation 1.26
125 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Cycle 1, Day 8	16.8 breaths/min	Standard Deviation 0.96
125 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Cycle 1, Day 1	17.5 breaths/min	Standard Deviation 0.58
170 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Cycle 1, Day 8	17.3 breaths/min	Standard Deviation 1.89
170 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Cycle 1, Day 1	18.1 breaths/min	Standard Deviation 0.83
170 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Cycle 2, Day 1	17.3 breaths/min	Standard Deviation 1.03
170 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Cycle 1, Day 15	17.7 breaths/min	Standard Deviation 0.82
170 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Cycle 1, Day 22	17.6 breaths/min	Standard Deviation 0.79
170 mg BID Intermittent Days 1 and 2 (Fasted)	Respiratory Rate	Baseline	18.1 breaths/min	Standard Deviation 0.83
170 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Cycle 1, Day 22	18.0 breaths/min	Standard Deviation 0
170 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Cycle 1, Day 15	17.4 breaths/min	Standard Deviation 0.89
170 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Cycle 1, Day 8	18.0 breaths/min	Standard Deviation 0
170 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Cycle 1, Day 1	17.6 breaths/min	Standard Deviation 0.89
170 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Cycle 2, Day 1	17.5 breaths/min	Standard Deviation 1
170 mg BID Intermittent Days 1 and 2 (Fed)	Respiratory Rate	Baseline	17.6 breaths/min	Standard Deviation 0.89
125 mg BID Intermittent Days 1 and 4 (Fasted)	Respiratory Rate	Cycle 2, Day 1	NA breaths/min	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Respiratory Rate	Cycle 1, Day 22	NA breaths/min	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Respiratory Rate	Baseline	NA breaths/min	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Respiratory Rate	Cycle 1, Day 15	NA breaths/min	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Respiratory Rate	Cycle 1, Day 8	NA breaths/min	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Respiratory Rate	Cycle 1, Day 1	NA breaths/min	—

Primary

Sitting Diastolic Blood Pressure

Time frame: 28 Days

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

Arm	Measure	Group	Value (MEAN)	Dispersion
35 mg BID Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 1	74.8 mmHg	Standard Deviation 9.43
35 mg BID Continuous	Sitting Diastolic Blood Pressure	Cycle 2, Day 1	72.0 mmHg	Standard Deviation 8
35 mg BID Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 22	72.5 mmHg	Standard Deviation 7.48
35 mg BID Continuous	Sitting Diastolic Blood Pressure	Baseline	72.8 mmHg	Standard Deviation 7.31
35 mg BID Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 15	74.7 mmHg	Standard Deviation 2.16
35 mg BID Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 8	74.5 mmHg	Standard Deviation 5.96
50 mg BID Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 15	72.8 mmHg	Standard Deviation 8.64
50 mg BID Continuous	Sitting Diastolic Blood Pressure	Baseline	75.4 mmHg	Standard Deviation 10.43
50 mg BID Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 1	77.4 mmHg	Standard Deviation 9.82
50 mg BID Continuous	Sitting Diastolic Blood Pressure	Cycle 2, Day 1	73.3 mmHg	Standard Deviation 10.49
50 mg BID Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 8	74.3 mmHg	Standard Deviation 8.58
50 mg BID Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 22	73.9 mmHg	Standard Deviation 9.37
75 mg QD Continuous	Sitting Diastolic Blood Pressure	Baseline	77.4 mmHg	Standard Deviation 7.71
75 mg QD Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 1	75.4 mmHg	Standard Deviation 6.91
75 mg QD Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 15	75.4 mmHg	Standard Deviation 7.86
75 mg QD Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 22	76.2 mmHg	Standard Deviation 6.2
75 mg QD Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 8	75.3 mmHg	Standard Deviation 8.84
75 mg QD Continuous	Sitting Diastolic Blood Pressure	Cycle 2, Day 1	72.7 mmHg	Standard Deviation 8.91
100 mg QD Continuous	Sitting Diastolic Blood Pressure	Cycle 2, Day 1	74.1 mmHg	Standard Deviation 7.36
100 mg QD Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 1	76.5 mmHg	Standard Deviation 8.03
100 mg QD Continuous	Sitting Diastolic Blood Pressure	Baseline	74.9 mmHg	Standard Deviation 8.36
100 mg QD Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 15	68.7 mmHg	Standard Deviation 7.12
100 mg QD Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 22	77.0 mmHg	Standard Deviation 5.4
100 mg QD Continuous	Sitting Diastolic Blood Pressure	Cycle 1, Day 8	72.6 mmHg	Standard Deviation 12.68
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 1	74.4 mmHg	Standard Deviation 11.68
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 22	70.9 mmHg	Standard Deviation 11.76
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 8	72.4 mmHg	Standard Deviation 11.77
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Baseline	74.4 mmHg	Standard Deviation 11.68
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 15	73.1 mmHg	Standard Deviation 11.09
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 2, Day 1	71.4 mmHg	Standard Deviation 10.43
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Cycle 1, Day 22	74.8 mmHg	Standard Deviation 10.24
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Cycle 1, Day 1	73.8 mmHg	Standard Deviation 8.62
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Cycle 1, Day 15	70.0 mmHg	Standard Deviation 7.87
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Cycle 2, Day 1	73.3 mmHg	Standard Deviation 4.57
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Baseline	73.8 mmHg	Standard Deviation 8.62
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Cycle 1, Day 8	70.8 mmHg	Standard Deviation 5.38
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 8	78.3 mmHg	Standard Deviation 10.64
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 1	75.5 mmHg	Standard Deviation 12.32
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 22	75.0 mmHg	Standard Deviation 12.4
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Baseline	75.5 mmHg	Standard Deviation 13.32
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 15	74.2 mmHg	Standard Deviation 14.11
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 2, Day 1	72.5 mmHg	Standard Deviation 12.42
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Baseline	76.6 mmHg	Standard Deviation 8.59
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Cycle 2, Day 1	68.0 mmHg	Standard Deviation 5.29
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Cycle 1, Day 22	73.2 mmHg	Standard Deviation 13.1
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Cycle 1, Day 8	75.8 mmHg	Standard Deviation 7.63
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Cycle 1, Day 15	69.0 mmHg	Standard Deviation 9.59
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Diastolic Blood Pressure	Cycle 1, Day 1	76.6 mmHg	Standard Deviation 8.59
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 15	NA mmHg	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 8	NA mmHg	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 1	NA mmHg	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 2, Day 1	NA mmHg	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Diastolic Blood Pressure	Cycle 1, Day 22	NA mmHg	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Diastolic Blood Pressure	Baseline	NA mmHg	—

Primary

Sitting Systolic Blood Pressure

Time frame: 28 Days

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

Arm	Measure	Group	Value (MEAN)	Dispersion
35 mg BID Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 15	119.7 mmHg	Standard Deviation 6.59
35 mg BID Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 1	113.5 mmHg	Standard Deviation 17.02
35 mg BID Continuous	Sitting Systolic Blood Pressure	Cycle 2, Day 1	111.7 mmHg	Standard Deviation 17.83
35 mg BID Continuous	Sitting Systolic Blood Pressure	Baseline	114.2 mmHg	Standard Deviation 9.13
35 mg BID Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 8	124.0 mmHg	Standard Deviation 5.93
35 mg BID Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 22	116.7 mmHg	Standard Deviation 12.09
50 mg BID Continuous	Sitting Systolic Blood Pressure	Baseline	126.3 mmHg	Standard Deviation 14.65
50 mg BID Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 15	115.5 mmHg	Standard Deviation 17.5
50 mg BID Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 8	120.4 mmHg	Standard Deviation 9.12
50 mg BID Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 22	124.7 mmHg	Standard Deviation 16.92
50 mg BID Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 1	125.1 mmHg	Standard Deviation 15.68
50 mg BID Continuous	Sitting Systolic Blood Pressure	Cycle 2, Day 1	119.7 mmHg	Standard Deviation 17.59
75 mg QD Continuous	Sitting Systolic Blood Pressure	Cycle 2, Day 1	123.6 mmHg	Standard Deviation 24.89
75 mg QD Continuous	Sitting Systolic Blood Pressure	Baseline	127.4 mmHg	Standard Deviation 14.09
75 mg QD Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 22	123.5 mmHg	Standard Deviation 21.17
75 mg QD Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 15	121.6 mmHg	Standard Deviation 17.68
75 mg QD Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 1	122.6 mmHg	Standard Deviation 18.05
75 mg QD Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 8	123.7 mmHg	Standard Deviation 16.41
100 mg QD Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 8	122.2 mmHg	Standard Deviation 20.67
100 mg QD Continuous	Sitting Systolic Blood Pressure	Baseline	125.2 mmHg	Standard Deviation 20.82
100 mg QD Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 15	115.2 mmHg	Standard Deviation 9.17
100 mg QD Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 1	124.7 mmHg	Standard Deviation 14.51
100 mg QD Continuous	Sitting Systolic Blood Pressure	Cycle 1, Day 22	125.4 mmHg	Standard Deviation 16.67
100 mg QD Continuous	Sitting Systolic Blood Pressure	Cycle 2, Day 1	116.6 mmHg	Standard Deviation 10.31
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 1	124.4 mmHg	Standard Deviation 19.04
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Cycle 2, Day 1	119.3 mmHg	Standard Deviation 17.81
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Baseline	124.4 mmHg	Standard Deviation 19.04
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 22	116.6 mmHg	Standard Deviation 16.62
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 15	122.8 mmHg	Standard Deviation 14.96
125 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 8	122.2 mmHg	Standard Deviation 13.88
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Baseline	122.3 mmHg	Standard Deviation 14.31
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Cycle 1, Day 22	115.5 mmHg	Standard Deviation 15.5
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Cycle 2, Day 1	112.5 mmHg	Standard Deviation 9
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Cycle 1, Day 8	115.3 mmHg	Standard Deviation 13.3
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Cycle 1, Day 1	122.3 mmHg	Standard Deviation 14.31
125 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Cycle 1, Day 15	112.8 mmHg	Standard Deviation 13.1
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Cycle 2, Day 1	113.2 mmHg	Standard Deviation 18.54
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 1	120.8 mmHg	Standard Deviation 17.65
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 8	127.9 mmHg	Standard Deviation 17.59
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Baseline	120.8 mmHg	Standard Deviation 17.65
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 22	119.9 mmHg	Standard Deviation 19.18
170 mg BID Intermittent Days 1 and 2 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 15	128.3 mmHg	Standard Deviation 15.87
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Cycle 1, Day 22	109.2 mmHg	Standard Deviation 8.32
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Cycle 1, Day 8	124.8 mmHg	Standard Deviation 21.56
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Cycle 1, Day 1	137.8 mmHg	Standard Deviation 19.18
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Baseline	137.8 mmHg	Standard Deviation 19.18
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Cycle 2, Day 1	117.0 mmHg	Standard Deviation 9.06
170 mg BID Intermittent Days 1 and 2 (Fed)	Sitting Systolic Blood Pressure	Cycle 1, Day 15	126.6 mmHg	Standard Deviation 10.97
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 1	NA mmHg	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 22	NA mmHg	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 15	NA mmHg	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Systolic Blood Pressure	Cycle 1, Day 8	NA mmHg	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Systolic Blood Pressure	Cycle 2, Day 1	NA mmHg	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Sitting Systolic Blood Pressure	Baseline	NA mmHg	—

Primary

Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant

Time frame: 15 Days

Arm	Measure	Value (MEDIAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	2.0 hours	Full Range 793.9
75 mg QD Continuous	Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	1.5 hours	Full Range 1440
100 mg QD Continuous	Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	3.0 hours	Full Range 838.4

Primary

Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant

Time frame: 22 Days

Arm	Measure	Value (MEDIAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	1.0 hours	Full Range 866
75 mg QD Continuous	Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	1.5 hours	Full Range 1305
100 mg QD Continuous	Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	1.5 hours	Full Range 1257

Secondary

Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.

Time frame: 1 Day

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.	4666 h*ng/mL	Geometric Coefficient of Variation 48.2
75 mg QD Continuous	Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.	8185 h*ng/mL	Geometric Coefficient of Variation 65.21
100 mg QD Continuous	Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.	11470 h*ng/mL	Geometric Coefficient of Variation 53.45

Secondary

Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.

Time frame: 1 Day

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
35 mg BID Continuous	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
50 mg BID Continuous	Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.	5543 h*ng/mL	Geometric Coefficient of Variation 63.41
75 mg QD Continuous	Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.	9843 h*ng/mL	Geometric Coefficient of Variation 75.43
100 mg QD Continuous	Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.	15110 h*ng/mL	Geometric Coefficient of Variation 63.32

Secondary

AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.

Time frame: 1 Day

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
35 mg BID Continuous	AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.	889.4 ng/mL	Geometric Coefficient of Variation 52.72
50 mg BID Continuous	AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.	968.5 ng/mL	Geometric Coefficient of Variation 36.45
75 mg QD Continuous	AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.	1678 ng/mL	Geometric Coefficient of Variation 55.72
100 mg QD Continuous	AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.	1942 ng/mL	Geometric Coefficient of Variation 56.46

Secondary

Best Objective Response (BOR)

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.

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
35 mg BID Continuous	Best Objective Response (BOR)	Complete Response	0 Participants
35 mg BID Continuous	Best Objective Response (BOR)	Partial Response	0 Participants
35 mg BID Continuous	Best Objective Response (BOR)	Stable Disease ≥ 8 weeks	1 Participants
35 mg BID Continuous	Best Objective Response (BOR)	Not Evaluable	0 Participants
35 mg BID Continuous	Best Objective Response (BOR)	Progression	1 Participants
50 mg BID Continuous	Best Objective Response (BOR)	Complete Response	0 Participants
50 mg BID Continuous	Best Objective Response (BOR)	Partial Response	2 Participants
50 mg BID Continuous	Best Objective Response (BOR)	Not Evaluable	3 Participants
50 mg BID Continuous	Best Objective Response (BOR)	Stable Disease ≥ 8 weeks	4 Participants
50 mg BID Continuous	Best Objective Response (BOR)	Progression	2 Participants
75 mg QD Continuous	Best Objective Response (BOR)	Not Evaluable	1 Participants
75 mg QD Continuous	Best Objective Response (BOR)	Progression	3 Participants
75 mg QD Continuous	Best Objective Response (BOR)	Stable Disease ≥ 8 weeks	7 Participants
75 mg QD Continuous	Best Objective Response (BOR)	Complete Response	0 Participants
75 mg QD Continuous	Best Objective Response (BOR)	Partial Response	2 Participants
100 mg QD Continuous	Best Objective Response (BOR)	Progression	0 Participants
100 mg QD Continuous	Best Objective Response (BOR)	Not Evaluable	2 Participants
100 mg QD Continuous	Best Objective Response (BOR)	Complete Response	0 Participants
100 mg QD Continuous	Best Objective Response (BOR)	Partial Response	1 Participants
100 mg QD Continuous	Best Objective Response (BOR)	Stable Disease ≥ 8 weeks	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Best Objective Response (BOR)	Progression	7 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Best Objective Response (BOR)	Complete Response	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Best Objective Response (BOR)	Not Evaluable	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Best Objective Response (BOR)	Partial Response	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Best Objective Response (BOR)	Stable Disease ≥ 8 weeks	17 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Best Objective Response (BOR)	Complete Response	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Best Objective Response (BOR)	Stable Disease ≥ 8 weeks	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Best Objective Response (BOR)	Progression	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Best Objective Response (BOR)	Not Evaluable	0 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Best Objective Response (BOR)	Partial Response	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Best Objective Response (BOR)	Complete Response	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Best Objective Response (BOR)	Progression	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Best Objective Response (BOR)	Stable Disease ≥ 8 weeks	3 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Best Objective Response (BOR)	Partial Response	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Best Objective Response (BOR)	Not Evaluable	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Best Objective Response (BOR)	Complete Response	0 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Best Objective Response (BOR)	Not Evaluable	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Best Objective Response (BOR)	Progression	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Best Objective Response (BOR)	Stable Disease ≥ 8 weeks	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Best Objective Response (BOR)	Partial Response	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Best Objective Response (BOR)	Not Evaluable	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Best Objective Response (BOR)	Complete Response	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Best Objective Response (BOR)	Stable Disease ≥ 8 weeks	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Best Objective Response (BOR)	Partial Response	1 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Best Objective Response (BOR)	Progression	0 Participants

Secondary

Clinical Benefit Rate (CBR) at 24 Weeks

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.

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
35 mg BID Continuous	Clinical Benefit Rate (CBR) at 24 Weeks	Yes	2 Participants
35 mg BID Continuous	Clinical Benefit Rate (CBR) at 24 Weeks	No	4 Participants
50 mg BID Continuous	Clinical Benefit Rate (CBR) at 24 Weeks	Yes	6 Participants
50 mg BID Continuous	Clinical Benefit Rate (CBR) at 24 Weeks	No	7 Participants
75 mg QD Continuous	Clinical Benefit Rate (CBR) at 24 Weeks	Yes	4 Participants
75 mg QD Continuous	Clinical Benefit Rate (CBR) at 24 Weeks	No	10 Participants
100 mg QD Continuous	Clinical Benefit Rate (CBR) at 24 Weeks	Yes	7 Participants
100 mg QD Continuous	Clinical Benefit Rate (CBR) at 24 Weeks	No	3 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinical Benefit Rate (CBR) at 24 Weeks	Yes	11 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Clinical Benefit Rate (CBR) at 24 Weeks	No	26 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinical Benefit Rate (CBR) at 24 Weeks	No	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Clinical Benefit Rate (CBR) at 24 Weeks	Yes	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinical Benefit Rate (CBR) at 24 Weeks	No	5 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Clinical Benefit Rate (CBR) at 24 Weeks	Yes	3 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinical Benefit Rate (CBR) at 24 Weeks	Yes	2 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Clinical Benefit Rate (CBR) at 24 Weeks	No	3 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinical Benefit Rate (CBR) at 24 Weeks	Yes	2 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Clinical Benefit Rate (CBR) at 24 Weeks	No	0 Participants

Secondary

Duration of Response (DoR)

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.

Time frame: Up to 12 months

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

Arm	Measure	Value (MEDIAN)
50 mg BID Continuous	Duration of Response (DoR)	5.1 Months
75 mg QD Continuous	Duration of Response (DoR)	9.7 Months
100 mg QD Continuous	Duration of Response (DoR)	NA Months
125 mg BID Intermittent Days 1 and 2 (Fasted)	Duration of Response (DoR)	NA Months
125 mg BID Intermittent Days 1 and 2 (Fed)	Duration of Response (DoR)	NA Months
170 mg BID Intermittent Days 1 and 2 (Fasted)	Duration of Response (DoR)	NA Months
125 mg BID Intermittent Days 1 and 4 (Fasted)	Duration of Response (DoR)	10.4 Months

Secondary

Objective Response Rate

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).

Time frame: 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.

Arm	Measure	Value (NUMBER)
35 mg BID Continuous	Objective Response Rate	0 Participants
50 mg BID Continuous	Objective Response Rate	2 Participants
75 mg QD Continuous	Objective Response Rate	2 Participants
100 mg QD Continuous	Objective Response Rate	1 Participants
125 mg BID Intermittent Days 1 and 2 (Fasted)	Objective Response Rate	2 Participants
125 mg BID Intermittent Days 1 and 2 (Fed)	Objective Response Rate	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fasted)	Objective Response Rate	1 Participants
170 mg BID Intermittent Days 1 and 2 (Fed)	Objective Response Rate	0 Participants
125 mg BID Intermittent Days 1 and 4 (Fasted)	Objective Response Rate	1 Participants

Secondary

Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.

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.

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
35 mg BID Continuous	Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	NA Percentage Change	—
50 mg BID Continuous	Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	-9.37 Percentage Change	Standard Deviation 39.544
75 mg QD Continuous	Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	-5.83 Percentage Change	Standard Deviation 52.781
100 mg QD Continuous	Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	NA Percentage Change	—
125 mg BID Intermittent Days 1 and 2 (Fasted)	Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	-0.46 Percentage Change	Standard Deviation 28.208
125 mg BID Intermittent Days 1 and 2 (Fed)	Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	-3.57 Percentage Change	Standard Deviation 28.476
170 mg BID Intermittent Days 1 and 2 (Fasted)	Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	-10.96 Percentage Change	Standard Deviation 19.012
170 mg BID Intermittent Days 1 and 2 (Fed)	Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	NA Percentage Change	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	NA Percentage Change	—

Secondary

Progression Free Survival

Time frame: 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.

Arm	Measure	Value (MEDIAN)	Dispersion
35 mg BID Continuous	Progression Free Survival	49.4 Weeks	—
50 mg BID Continuous	Progression Free Survival	35.6 Weeks	80% Confidence Interval 39.544
75 mg QD Continuous	Progression Free Survival	17.3 Weeks	80% Confidence Interval 52.781
100 mg QD Continuous	Progression Free Survival	78.3 Weeks	—
125 mg BID Intermittent Days 1 and 2 (Fasted)	Progression Free Survival	22.6 Weeks	80% Confidence Interval 28.208
125 mg BID Intermittent Days 1 and 2 (Fed)	Progression Free Survival	33.9 Weeks	80% Confidence Interval 28.476
170 mg BID Intermittent Days 1 and 2 (Fasted)	Progression Free Survival	60.1 Weeks	80% Confidence Interval 19.012
170 mg BID Intermittent Days 1 and 2 (Fed)	Progression Free Survival	83.4 Weeks	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Progression Free Survival	NA Weeks	—

Secondary

Progression Free Survival at 26 Weeks

Time frame: 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.

Arm	Measure	Value (NUMBER)	Dispersion
35 mg BID Continuous	Progression Free Survival at 26 Weeks	33 Percentage	—
50 mg BID Continuous	Progression Free Survival at 26 Weeks	38 Percentage	80% Confidence Interval 39.544
75 mg QD Continuous	Progression Free Survival at 26 Weeks	21 Percentage	80% Confidence Interval 52.781
100 mg QD Continuous	Progression Free Survival at 26 Weeks	60 Percentage	—
125 mg BID Intermittent Days 1 and 2 (Fasted)	Progression Free Survival at 26 Weeks	35 Percentage	80% Confidence Interval 28.208
125 mg BID Intermittent Days 1 and 2 (Fed)	Progression Free Survival at 26 Weeks	50 Percentage	80% Confidence Interval 28.476
170 mg BID Intermittent Days 1 and 2 (Fasted)	Progression Free Survival at 26 Weeks	38 Percentage	80% Confidence Interval 19.012
170 mg BID Intermittent Days 1 and 2 (Fed)	Progression Free Survival at 26 Weeks	40 Percentage	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Progression Free Survival at 26 Weeks	100 Percentage	—

Secondary

Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.

Time frame: 1 Day

Arm	Measure	Value (MEDIAN)	Dispersion
35 mg BID Continuous	Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.	1.00 hour	Full Range 52.72
50 mg BID Continuous	Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.	1.00 hour	Full Range 36.45
75 mg QD Continuous	Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.	1.10 hour	Full Range 55.72
100 mg QD Continuous	Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.	1.80 hour	Full Range 56.46

Source: ClinicalTrials.gov · Data processed: Mar 1, 2026

Arm	Measure	Group	Value (MEAN)	Dispersion
35 mg BID Continuous	Left Ventricular Ejection Fraction	Screening	59.2 % Left Ventricular Ejection Fraction	Standard Deviation 4.5
35 mg BID Continuous	Left Ventricular Ejection Fraction	End of Study	NA % Left Ventricular Ejection Fraction	—
35 mg BID Continuous	Left Ventricular Ejection Fraction	Change from Baseline to End of Study	NA % Left Ventricular Ejection Fraction	—
50 mg BID Continuous	Left Ventricular Ejection Fraction	Change from Baseline to End of Study	1.4 % Left Ventricular Ejection Fraction	Standard Deviation 5.9
50 mg BID Continuous	Left Ventricular Ejection Fraction	End of Study	64.0 % Left Ventricular Ejection Fraction	Standard Deviation 2
50 mg BID Continuous	Left Ventricular Ejection Fraction	Screening	64.0 % Left Ventricular Ejection Fraction	Standard Deviation 5.4
75 mg QD Continuous	Left Ventricular Ejection Fraction	End of Study	62.3 % Left Ventricular Ejection Fraction	Standard Deviation 4.1
75 mg QD Continuous	Left Ventricular Ejection Fraction	Change from Baseline to End of Study	-1.5 % Left Ventricular Ejection Fraction	Standard Deviation 2.4
75 mg QD Continuous	Left Ventricular Ejection Fraction	Screening	60.9 % Left Ventricular Ejection Fraction	Standard Deviation 6.2
100 mg QD Continuous	Left Ventricular Ejection Fraction	Change from Baseline to End of Study	0.0 % Left Ventricular Ejection Fraction	Standard Deviation 7.6
100 mg QD Continuous	Left Ventricular Ejection Fraction	Screening	61.4 % Left Ventricular Ejection Fraction	Standard Deviation 9.8
100 mg QD Continuous	Left Ventricular Ejection Fraction	End of Study	61.8 % Left Ventricular Ejection Fraction	Standard Deviation 8.3
125 mg BID Intermittent Days 1 and 2 (Fasted)	Left Ventricular Ejection Fraction	End of Study	62.5 % Left Ventricular Ejection Fraction	Standard Deviation 2.9
125 mg BID Intermittent Days 1 and 2 (Fasted)	Left Ventricular Ejection Fraction	Screening	62.6 % Left Ventricular Ejection Fraction	Standard Deviation 4.1
125 mg BID Intermittent Days 1 and 2 (Fasted)	Left Ventricular Ejection Fraction	Change from Baseline to End of Study	-1.3 % Left Ventricular Ejection Fraction	Standard Deviation 3.9
125 mg BID Intermittent Days 1 and 2 (Fed)	Left Ventricular Ejection Fraction	End of Study	NA % Left Ventricular Ejection Fraction	—
125 mg BID Intermittent Days 1 and 2 (Fed)	Left Ventricular Ejection Fraction	Screening	62.5 % Left Ventricular Ejection Fraction	Standard Deviation 2.9
125 mg BID Intermittent Days 1 and 2 (Fed)	Left Ventricular Ejection Fraction	Change from Baseline to End of Study	NA % Left Ventricular Ejection Fraction	—
170 mg BID Intermittent Days 1 and 2 (Fasted)	Left Ventricular Ejection Fraction	Change from Baseline to End of Study	NA % Left Ventricular Ejection Fraction	—
170 mg BID Intermittent Days 1 and 2 (Fasted)	Left Ventricular Ejection Fraction	Screening	66.9 % Left Ventricular Ejection Fraction	Standard Deviation 4.6
170 mg BID Intermittent Days 1 and 2 (Fasted)	Left Ventricular Ejection Fraction	End of Study	NA % Left Ventricular Ejection Fraction	—
170 mg BID Intermittent Days 1 and 2 (Fed)	Left Ventricular Ejection Fraction	End of Study	NA % Left Ventricular Ejection Fraction	—
170 mg BID Intermittent Days 1 and 2 (Fed)	Left Ventricular Ejection Fraction	Change from Baseline to End of Study	NA % Left Ventricular Ejection Fraction	—
170 mg BID Intermittent Days 1 and 2 (Fed)	Left Ventricular Ejection Fraction	Screening	63.8 % Left Ventricular Ejection Fraction	Standard Deviation 5.2
125 mg BID Intermittent Days 1 and 4 (Fasted)	Left Ventricular Ejection Fraction	End of Study	NA % Left Ventricular Ejection Fraction	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Left Ventricular Ejection Fraction	Change from Baseline to End of Study	NA % Left Ventricular Ejection Fraction	—
125 mg BID Intermittent Days 1 and 4 (Fasted)	Left Ventricular Ejection Fraction	Screening	NA % Left Ventricular Ejection Fraction	—

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

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Adverse Events

Adverse Events Leading to Dose Reduction of AZD2014

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant

AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant

Body Temperature

Clinically Important Changes in Clinical Chemistry Parameters

Clinically Important Changes in Haematology Parameters

Heart Rate

Left Ventricular Ejection Fraction

Oxygen Saturation

Post-Baseline Glucose Elevation

QTcF Over 24 Hours

Respiratory Rate

Sitting Diastolic Blood Pressure

Sitting Systolic Blood Pressure

Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant

Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant

Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.

Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.

AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.

Best Objective Response (BOR)

Clinical Benefit Rate (CBR) at 24 Weeks

Duration of Response (DoR)

Objective Response Rate

Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.

Progression Free Survival

Progression Free Survival at 26 Weeks

Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.