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A Study to Investigate Efficacy and Safety With Oral AZD9833 Compared With Intramuscular Fulvestrant in Post-menopausal Women at Least 18 Years of Age With Advanced ER-positive HER2 Negative Breast Cancer (SERENA-2)

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ClinicalTrials.gov Identifier: NCT04214288
Recruitment Status : Active, not recruiting
First Posted : January 2, 2020
Results First Posted : December 12, 2023
Last Update Posted : May 13, 2024
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Advanced ER-Positive HER2-Negative Breast Cancer
Interventions Drug: AZD9833
Drug: Fulvestrant
Enrollment 240
Recruitment Details The patients were enrolled at 82 sites in 16 countries from 22 April 2020 to 30 August 2022. The study is ongoing.
Pre-assignment Details  
Arm/Group Title AZD9833 75mg AZD9833 150mg AZD9833 300mg Fulvestrant 500 mg
Hide Arm/Group Description The patients received AZD9833 75mg oral tablets once daily. The patients received AZD9833 150mg oral tablets once daily. The patients received AZD9833 300mg oral tablets once daily. The patients received Fulvestrant 500 mg via Intramuscular (IM) injection.
Period Title: Overall Study
Started 74 73 20 73
Completed 0 0 0 0
Not Completed 74 73 20 73
Reason Not Completed
Ongoing in the study             41             51             12             39
Adverse Event             1             0             0             0
Death             22             13             7             19
Lost to Follow-up             1             2             1             0
Other             1             2             0             6
Protocol Violation             0             1             0             0
Withdrawal by Subject             8             4             0             9
Arm/Group Title AZD9833 75mg AZD9833 150mg AZD9833 300mg Fulvestrant 500 mg Total
Hide Arm/Group Description The patients received AZD9833 75mg oral tablets once daily. The patients received AZD9833 150mg oral tablets once daily. The patients received AZD9833 300mg oral tablets once daily. The patients received Fulvestrant 500 mg via IM injection. Total of all reporting groups
Overall Number of Baseline Participants 74 73 20 73 240
Hide Baseline Analysis Population Description
Full Analysis Set (FAS) consisted of all randomised patients, with treatment groups assigned in accordance with the randomisation, regardless of the actual treatment received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 74 participants 73 participants 20 participants 73 participants 240 participants
61.2  (9.56) 61.7  (9.68) 59.9  (10.72) 59.3  (11.08) 60.7  (10.16)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 74 participants 73 participants 20 participants 73 participants 240 participants
Female
74
 100.0%
73
 100.0%
20
 100.0%
73
 100.0%
240
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 74 participants 73 participants 20 participants 73 participants 240 participants
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.7%
2
   0.8%
White
71
  95.9%
70
  95.9%
20
 100.0%
65
  89.0%
226
  94.2%
Other
3
   4.1%
3
   4.1%
0
   0.0%
6
   8.2%
12
   5.0%
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description

PFS was assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1. PFS was defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or received another anti-cancer therapy prior to progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.

Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.
Time Frame From date of randomisation to date of objective disease progression (or last evaluable assessment in the absence of progression) or death (up to data cut-off of 29 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS consisted of all randomised patients, with treatment groups assigned in accordance with the randomisation, regardless of the actual treatment received.
Arm/Group Title AZD9833 75mg AZD9833 150mg AZD9833 300mg Fulvestrant 500 mg
Hide Arm/Group Description:
The patients received AZD9833 75mg oral tablets once daily.
The patients received AZD9833 150mg oral tablets once daily.
The patients received AZD9833 300mg oral tablets once daily.
The patients received Fulvestrant 500 mg via IM injection.
Overall Number of Participants Analyzed 74 73 20 73
Median (90% Confidence Interval)
Unit of Measure: Months
7.2
(3.7 to 10.9)
7.7
(5.5 to 12.9)
6.3 [1] 
(1.9 to NA)
3.7
(2.0 to 6.0)
[1]
The upper limit of 90% confidence interval (CI) was not estimable due to insufficient data.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD9833 75mg, Fulvestrant 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0167
Comments [Not Specified]
Method Log Rank
Comments The analysis was performed using a stratified Cox Proportional Hazards model.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.59
Confidence Interval 90%
0.42 to 0.82
Estimation Comments A hazard ratio < 1 favours AZD9833 to be associated with a longer progression-free survival than fulvestrant.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD9833 150mg, Fulvestrant 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0090
Comments [Not Specified]
Method Log Rank
Comments The analysis was performed using a stratified Cox Proportional Hazards model.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.64
Confidence Interval 90%
0.46 to 0.89
Estimation Comments A hazard ratio < 1 favours AZD9833 to be associated with a longer progression-free survival than fulvestrant.
2.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description

ORR was assessed by the Investigator as defined by RECIST version 1.1. The ORR was defined as investigator assessed Complete Response or Partial Response prior to progression in patients with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Adjusted response rate was presented in this analysis.

Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.
Time Frame From screening until disease progression (up to data cut-off of 29 months)
Hide Outcome Measure Data
Hide Analysis Population Description
A subset of the FAS with measurable disease.
Arm/Group Title AZD9833 75mg AZD9833 150mg AZD9833 300mg Fulvestrant 500 mg
Hide Arm/Group Description:
The patients received AZD9833 75mg oral tablets once daily.
The patients received AZD9833 150mg oral tablets once daily.
The patients received AZD9833 300mg oral tablets once daily.
The patients received Fulvestrant 500 mg via IM injection.
Overall Number of Participants Analyzed 70 65 19 68
Measure Type: Number
Unit of Measure: Percentage (%)
15.7 17.1 25.2 11.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD9833 75mg, Fulvestrant 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4828
Comments [Not Specified]
Method Regression, Logistic
Comments The analysis was performed using logistic regression model adjusting for prior use of CDK4/6 inhibitors and presence of lung and/or liver metastasis.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.42
Confidence Interval 90%
0.63 to 3.31
Estimation Comments An odds ratio > 1 favours AZD9833.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD9833 150mg, Fulvestrant 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3691
Comments [Not Specified]
Method Regression, Logistic
Comments The analysis was performed using logistic regression model adjusting for prior use of CDK4/6 inhibitors and presence of lung and/or liver metastasis.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.57
Confidence Interval 90%
0.69 to 3.67
Estimation Comments An odds ratio > 1 favours AZD9833.
3.Secondary Outcome
Title Duration of Response (DoR)
Hide Description DoR was assessed by the Investigator as defined by RECIST version 1.1. The DoR was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.
Time Frame From screening until disease progression or last evaluable assessment in the absence of progression (up to data cut-off of 29 months)
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Percentage Change in Tumour Size at 16 Weeks
Hide Description The percentage change in tumour size at 16 weeks was obtained for each patient, based on RECIST measurements taken at baseline and at 16 weeks. Tumour size is the sum of the longest diameters of the target lesions (TLs). Percentage change in the sum of longest TLs diameters at 16 weeks was measured.
Time Frame At Week 16
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description The OS was defined as the time from randomisation to death due to any cause.
Time Frame From the date of randomisation until death (up to data cut-off of 29 months)
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Clinical Benefit Rate at 24 Weeks (CBR24)
Hide Description

Clinical benefit rate was defined as patients with best objective response of complete response or partial response in the first 25 weeks or who have stable disease for at least 23 weeks after randomization.

Adjusted response rate was presented in this analysis.

Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.
Time Frame At Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS consisted of all randomised patients, with treatment groups assigned in accordance with the randomisation, regardless of the actual treatment received.
Arm/Group Title AZD9833 75mg AZD9833 150mg AZD9833 300mg Fulvestrant 500 mg
Hide Arm/Group Description:
The patients received AZD9833 75mg oral tablets once daily.
The patients received AZD9833 150mg oral tablets once daily.
The patients received AZD9833 300mg oral tablets once daily.
The patients received Fulvestrant 500 mg via IM injection.
Overall Number of Participants Analyzed 74 73 20 73
Measure Type: Number
Unit of Measure: Percentage (%)
48.8 51.0 42.4 39.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD9833 75mg, Fulvestrant 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2554
Comments [Not Specified]
Method Regression, Logistic
Comments The analysis was performed using logistic regression model adjusting for prior use of CDK4/6 inhibitors and presence of lung and/or liver metastasis.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.48
Confidence Interval (2-Sided) 90%
0.84 to 2.64
Estimation Comments An odds ratio > 1 favours AZD9833.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD9833 150mg, Fulvestrant 500 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1658
Comments [Not Specified]
Method Regression, Logistic
Comments The analysis was performed using logistic regression model adjusting for prior use of CDK4/6 inhibitors and presence of lung and/or liver metastasis.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.62
Confidence Interval 90%
0.91 to 2.89
Estimation Comments An odds ratio > 1 favours AZD9833.
7.Secondary Outcome
Title Plasma Concentrations of AZD9833
Hide Description The plasma concentrations of AZD9833 at steady state were evaluated.
Time Frame Cycle 1 Day 15 (pre-dose), Cycle 1 Day 15 (2h), Cycle 1 Day 15 (4h) and Cycle 2 Day 1 (pre-dose), (each cycle is 28 days in length)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Analysis Set consisted of all patients who received at least one dose of AZD9833 per protocol, for whom there is at least one reportable PK concentration.
Arm/Group Title AZD9833 75mg AZD9833 150mg AZD9833 300mg
Hide Arm/Group Description:
The patients received AZD9833 75mg oral tablets once daily.
The patients received AZD9833 150mg oral tablets once daily.
The patients received AZD9833 300mg oral tablets once daily.
Overall Number of Participants Analyzed 69 68 19
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/ml
Cycle 1 Day 15 (pre-dose) Number Analyzed 69 participants 67 participants 18 participants
22.8387
(84.3207%)
41.0856
(148.5806%)
108.1351
(157.3080%)
Cycle 1 Day 15 (2h) Number Analyzed 69 participants 64 participants 18 participants
51.9098
(94.4632%)
96.2038
(164.5328%)
302.1254
(66.9155%)
Cycle 1 Day 15 (4h) Number Analyzed 69 participants 62 participants 19 participants
54.5098
(87.2152%)
95.5360
(160.0032%)
289.1464
(68.1607%)
Cycle 2 Day 1 (pre-dose) Number Analyzed 64 participants 68 participants 18 participants
24.2895
(88.4140%)
34.2592
(245.9897%)
115.8558
(156.4858%)
8.Secondary Outcome
Title Percent Change From Baseline in ER and PgR Expression and Ki67 Labelling Index
Hide Description The pharmacodynamics of AZD9833 and fulvestrant in a subgroup of patients.
Time Frame From baseline to Cycle 2 Day 1 (each cycle is 28 days in length)
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Changes From Baseline in Health Related Quality of Life (HRQoL)
Hide Description To evaluate the effect of AZD9833 and fulvestrant on the patients' health-related quality of life, as assessed by patient completed HRQoL questionnaires.
Time Frame From Day 1 until end of treatment and safety follow up (up to data cut-off of 29 months)
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title Number of Patients With Adverse Events
Hide Description The safety and tolerability of AZD9833 when compared to fulvestrant in women with advanced ER-positive HER2-negative breast cancer was evaluated.
Time Frame From the date of first dose up to the safety follow-up period (28 days after last dose of AZD9833 and 56 days after last dose of fulvestrant) (up to data cut-off of 29 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all patients who received any amount of study treatment (AZD9833 or fulvestrant), regardless of whether that was the randomised therapy intended or whether they received therapy without being randomised and for whom any post-dose data are available.
Arm/Group Title AZD9833 75mg AZD9833 150mg AZD9833 300mg Fulvestrant 500 mg
Hide Arm/Group Description:
The patients received AZD9833 75mg oral tablets once daily.
The patients received AZD9833 150mg oral tablets once daily.
The patients received AZD9833 300mg oral tablets once daily.
The patients received Fulvestrant 500 mg via IM injection.
Overall Number of Participants Analyzed 74 73 20 73
Measure Type: Count of Participants
Unit of Measure: Participants
Any Adverse Event (AE)
57
  77.0%
66
  90.4%
19
  95.0%
50
  68.5%
Any AE causally related to treatment
39
  52.7%
49
  67.1%
14
  70.0%
13
  17.8%
Any AE of CTCAE grade 3 or higher
9
  12.2%
17
  23.3%
3
  15.0%
11
  15.1%
Any AE of CTCAE grade 3 or higher, causally related to treatment
1
   1.4%
2
   2.7%
1
   5.0%
0
   0.0%
Any AE with outcome = death
0
   0.0%
1
   1.4%
0
   0.0%
0
   0.0%
Any AE with outcome = death, causally related to treatment
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Any Serious Adverse Event (SAE)
6
   8.1%
7
   9.6%
2
  10.0%
4
   5.5%
Any SAE, causally related to treatment
3
   4.1%
2
   2.7%
1
   5.0%
0
   0.0%
Any SAE causing discontinuation of treatment
1
   1.4%
0
   0.0%
0
   0.0%
0
   0.0%
Any SAE causing discontinuation of treatment, causally related to treatment
1
   1.4%
0
   0.0%
0
   0.0%
0
   0.0%
Any AE leading to discontinuation of treatment
2
   2.7%
0
   0.0%
2
  10.0%
0
   0.0%
Any AE leading to discontinuation of treatment, causally related to treatment
2
   2.7%
0
   0.0%
0
   0.0%
0
   0.0%
Any AE leading to dose reduction
1
   1.4%
9
  12.3%
4
  20.0%
0
   0.0%
Any AE leading to dose interruption
11
  14.9%
16
  21.9%
4
  20.0%
3
   4.1%
Time Frame From the date of first dose up to the safety follow-up period (28 days after last dose of AZD9833 and 56 days after last dose of fulvestrant) (up to data cut-off of 29 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AZD9833 75mg AZD9833 150mg AZD9833 300mg Fulvestrant 500 mg
Hide Arm/Group Description The patients received AZD9833 75mg oral tablets once daily. The patients received AZD9833 150mg oral tablets once daily. The patients received AZD9833 300mg oral tablets once daily. The patients received Fulvestrant 500 mg via IM injection.
All-Cause Mortality
AZD9833 75mg AZD9833 150mg AZD9833 300mg Fulvestrant 500 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   23/74 (31.08%)      14/73 (19.18%)      7/20 (35.00%)      21/73 (28.77%)    
Hide Serious Adverse Events
AZD9833 75mg AZD9833 150mg AZD9833 300mg Fulvestrant 500 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/74 (8.11%)      7/73 (9.59%)      2/20 (10.00%)      4/73 (5.48%)    
Blood and lymphatic system disorders         
Anaemia † 1  1/74 (1.35%)  1 0/73 (0.00%)  0 0/20 (0.00%)  0 0/73 (0.00%)  0
Cardiac disorders         
Atrial fibrillation † 1  0/74 (0.00%)  0 1/73 (1.37%)  1 0/20 (0.00%)  0 1/73 (1.37%)  1
Atrial tachycardia † 1  0/74 (0.00%)  0 1/73 (1.37%)  1 0/20 (0.00%)  0 0/73 (0.00%)  0
Supraventricular tachycardia † 1  0/74 (0.00%)  0 0/73 (0.00%)  0 0/20 (0.00%)  0 1/73 (1.37%)  1
Eye disorders         
Eyelid oedema † 1  1/74 (1.35%)  1 0/73 (0.00%)  0 0/20 (0.00%)  0 0/73 (0.00%)  0
Gastrointestinal disorders         
Dysphagia † 1  0/74 (0.00%)  0 1/73 (1.37%)  1 0/20 (0.00%)  0 0/73 (0.00%)  0
Nausea † 1  0/74 (0.00%)  0 1/73 (1.37%)  1 0/20 (0.00%)  0 0/73 (0.00%)  0
Oesophageal obstruction † 1  1/74 (1.35%)  1 1/73 (1.37%)  1 0/20 (0.00%)  0 0/73 (0.00%)  0
General disorders         
Swelling face † 1  1/74 (1.35%)  1 0/73 (0.00%)  0 0/20 (0.00%)  0 0/73 (0.00%)  0
Hepatobiliary disorders         
Cholecystitis acute † 1  1/74 (1.35%)  1 0/73 (0.00%)  0 0/20 (0.00%)  0 0/73 (0.00%)  0
Infections and infestations         
Breast cellulitis † 1  0/74 (0.00%)  0 1/7 (14.29%)  1 0/20 (0.00%)  0 0/73 (0.00%)  0
COVID-19 † 1  0/74 (0.00%)  0 0/7 (0.00%)  0 1/20 (5.00%)  1 0/73 (0.00%)  0
COVID-19 pneumonia † 1  0/74 (0.00%)  0 1/7 (14.29%)  1 0/20 (0.00%)  0 0/73 (0.00%)  0
Injury, poisoning and procedural complications         
Femur fracture † 1  0/74 (0.00%)  0 0/73 (0.00%)  0 0/20 (0.00%)  0 1/73 (1.37%)  1
Lower limb fracture † 1  0/74 (0.00%)  0 1/73 (1.37%)  1 0/20 (0.00%)  0 0/73 (0.00%)  0
Investigations         
Blood pressure increased † 1  0/74 (0.00%)  0 1/73 (1.37%)  1 0/20 (0.00%)  0 0/73 (0.00%)  0
International normalised ratio increased † 1  0/74 (0.00%)  0 0/73 (0.00%)  0 1/20 (5.00%)  1 0/73 (0.00%)  0
Metabolism and nutrition disorders         
Hypervolaemia † 1  1/74 (1.35%)  1 0/73 (0.00%)  0 0/20 (0.00%)  0 0/73 (0.00%)  0
Hyponatraemia † 1  0/74 (0.00%)  0 1/73 (1.37%)  1 0/20 (0.00%)  0 0/73 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Pathological fracture † 1  0/74 (0.00%)  0 0/73 (0.00%)  0 0/20 (0.00%)  0 1/73 (1.37%)  1
Nervous system disorders         
Cerebrovascular accident † 1  0/74 (0.00%)  0 1/73 (1.37%)  1 0/20 (0.00%)  0 0/73 (0.00%)  0
Renal and urinary disorders         
Anuria † 1  0/74 (0.00%)  0 0/73 (0.00%)  0 0/20 (0.00%)  0 1/73 (1.37%)  1
Respiratory, thoracic and mediastinal disorders         
Pleural effusion † 1  0/74 (0.00%)  0 1/73 (1.37%)  1 0/20 (0.00%)  0 1/73 (1.37%)  1
Vascular disorders         
Hypertension † 1  1/74 (1.35%)  1 0/73 (0.00%)  0 0/20 (0.00%)  0 0/73 (0.00%)  0
1
Term from vocabulary, MedDRA version 26.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AZD9833 75mg AZD9833 150mg AZD9833 300mg Fulvestrant 500 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   44/74 (59.46%)      61/73 (83.56%)      17/20 (85.00%)      31/73 (42.47%)    
Blood and lymphatic system disorders         
Anaemia † 1  7/74 (9.46%)  8 11/73 (15.07%)  16 1/20 (5.00%)  1 5/73 (6.85%)  11
Thrombocytopenia † 1  1/74 (1.35%)  1 4/73 (5.48%)  4 1/20 (5.00%)  1 2/73 (2.74%)  3
Cardiac disorders         
Bradycardia † 1  0/74 (0.00%)  0 12/73 (16.44%)  12 6/20 (30.00%)  8 0/73 (0.00%)  0
Sinus bradycardia † 1  4/74 (5.41%)  4 7/73 (9.59%)  10 2/20 (10.00%)  2 0/73 (0.00%)  0
Eye disorders         
Cataract † 1  2/74 (2.70%)  2 0/73 (0.00%)  0 2/20 (10.00%)  2 0/73 (0.00%)  0
Photopsia † 1  9/74 (12.16%)  11 18/73 (24.66%)  28 7/20 (35.00%)  10 0/73 (0.00%)  0
Visual impairment † 1  5/74 (6.76%)  5 5/73 (6.85%)  5 1/20 (5.00%)  1 0/73 (0.00%)  0
Vitreous floaters † 1  2/74 (2.70%)  2 0/73 (0.00%)  0 2/20 (10.00%)  2 0/73 (0.00%)  0
Gastrointestinal disorders         
Constipation † 1  3/74 (4.05%)  3 5/73 (6.85%)  5 0/20 (0.00%)  0 1/73 (1.37%)  2
Diarrhoea † 1  4/74 (5.41%)  4 4/73 (5.48%)  4 3/20 (15.00%)  3 2/73 (2.74%)  2
Dyspepsia † 1  1/74 (1.35%)  1 3/73 (4.11%)  3 2/20 (10.00%)  3 1/73 (1.37%)  1
Nausea † 1  6/74 (8.11%)  9 4/73 (5.48%)  4 1/20 (5.00%)  1 2/73 (2.74%)  3
General disorders         
Asthenia † 1  6/74 (8.11%)  6 11/73 (15.07%)  13 2/20 (10.00%)  3 5/73 (6.85%)  5
Fatigue † 1  4/74 (5.41%)  4 14/73 (19.18%)  19 4/20 (20.00%)  4 3/73 (4.11%)  3
Pyrexia † 1  2/74 (2.70%)  3 4/73 (5.48%)  4 0/20 (0.00%)  0 1/73 (1.37%)  3
Infections and infestations         
COVID-19 † 1  4/74 (5.41%)  4 4/73 (5.48%)  4 2/20 (10.00%)  2 3/73 (4.11%)  3
Urinary tract infection † 1  5/74 (6.76%)  6 3/73 (4.11%)  4 0/20 (0.00%)  0 1/73 (1.37%)  1
Investigations         
Alanine aminotransferase increased † 1  1/74 (1.35%)  2 6/73 (8.22%)  10 3/20 (15.00%)  4 4/73 (5.48%)  6
Aspartate aminotransferase increased † 1  2/74 (2.70%)  2 6/73 (8.22%)  10 2/20 (10.00%)  2 5/73 (6.85%)  6
Blood creatine phosphokinase increased † 1  0/74 (0.00%)  0 4/73 (5.48%)  4 1/20 (5.00%)  1 1/73 (1.37%)  1
Blood pressure increased † 1  2/74 (2.70%)  3 1/73 (1.37%)  1 2/20 (10.00%)  5 0/73 (0.00%)  0
Metabolism and nutrition disorders         
Decreased appetite † 1  4/74 (5.41%)  4 1/73 (1.37%)  1 1/20 (5.00%)  1 2/73 (2.74%)  2
Hyponatraemia † 1  0/74 (0.00%)  0 2/73 (2.74%)  4 2/20 (10.00%)  2 1/73 (1.37%)  1
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  3/74 (4.05%)  6 9/73 (12.33%)  11 2/20 (10.00%)  2 3/73 (4.11%)  6
Back pain † 1  3/74 (4.05%)  3 2/73 (2.74%)  2 2/20 (10.00%)  3 5/73 (6.85%)  5
Bone pain † 1  2/74 (2.70%)  2 3/73 (4.11%)  3 0/20 (0.00%)  0 4/73 (5.48%)  4
Pain in extremity † 1  1/74 (1.35%)  1 4/73 (5.48%)  4 2/20 (10.00%)  2 3/73 (4.11%)  4
Nervous system disorders         
Dizziness † 1  4/74 (5.41%)  6 3/73 (4.11%)  3 1/20 (5.00%)  2 1/73 (1.37%)  1
Headache † 1  5/74 (6.76%)  6 6/72 (8.33%)  8 1/20 (5.00%)  1 2/73 (2.74%)  2
Psychiatric disorders         
Insomnia † 1  1/74 (1.35%)  1 3/73 (4.11%)  5 2/20 (10.00%)  2 1/73 (1.37%)  1
Respiratory, thoracic and mediastinal disorders         
Cough † 1  7/74 (9.46%)  8 1/73 (1.37%)  1 1/20 (5.00%)  1 3/73 (4.11%)  4
Dyspnoea † 1  2/74 (2.70%)  2 7/73 (9.59%)  7 1/20 (5.00%)  1 3/73 (4.11%)  3
Vascular disorders         
Hot flush † 1  4/74 (5.41%)  4 3/73 (4.11%)  3 1/20 (5.00%)  1 2/73 (2.74%)  2
Hypertension † 1  0/74 (0.00%)  0 6/73 (8.22%)  7 0/20 (0.00%)  0 1/73 (1.37%)  1
1
Term from vocabulary, MedDRA version 26.0
†
Indicates events were collected by systematic assessment

At the time of CSR finalization, CSP version 5.0 was available, therefore, CSP version 5.0 was redacted and submitted along with the Results Registration Form.

Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Lead
Organization: AstraZeneca
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04214288    
Other Study ID Numbers: D8530C00002
2019-003706-27 ( EudraCT Number )
First Submitted: December 27, 2019
First Posted: January 2, 2020
Results First Submitted: August 23, 2023
Results First Posted: December 12, 2023
Last Update Posted: May 13, 2024