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A Dose-Ranging Study With Vupanorsen (TRANSLATE-TIMI 70)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04516291
Recruitment Status : Completed
First Posted : August 18, 2020
Results First Posted : October 4, 2022
Last Update Posted : October 4, 2022
Sponsor:
Collaborator:
TIMI Study Group
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Dyslipidemias
Hyperlipidemias
Hyperlipoproteinemias
Interventions Drug: Vupanorsen
Drug: Placebo
Enrollment 286
Recruitment Details Adult participants aged greater than equal to (>=) 40 years with dyslipidemia on a stable dose of statin (with or without ezetimibe) were included in the study. The study was conducted across 3 countries.
Pre-assignment Details 727 participants signed the inform consent form (ICF). 391 participants were screen failures who did not meet criteria and were not enrolled. 336 participants were enrolled into the study of which 50 participants were not randomized and 286 participants were assigned to a study treatment.
Arm/Group Title Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
Hide Arm/Group Description Participants were randomized to receive vupanorsen (PF-07285557) matched placebo subcutaneous (SC) injection. Single or double administration was given at every 2 or 4 weeks (Q2W or Q4W) to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Period Title: Treatment Period (24 Weeks)
Started 44 23 24 23 45 45 46 36
Completed 42 18 20 17 33 37 37 22
Not Completed 2 5 4 6 12 8 9 14
Reason Not Completed
Other             1             0             0             2             2             4             2             0
Withdrawal by Subject             0             2             1             0             1             0             0             0
Protocol Violation             0             0             0             1             0             0             0             0
Lost to Follow-up             0             1             0             0             0             0             0             0
Adverse Event             1             2             3             3             9             4             7             14
Period Title: Follow-up Period (12 Weeks)
Started 44 [1] 23 [1] 24 [1] 23 [1] 45 [1] 45 [1] 46 [1] 36 [1]
Completed 44 22 23 21 43 45 46 36
Not Completed 0 1 1 2 2 0 0 0
Reason Not Completed
Other             0             1             0             2             0             0             0             0
Withdrawal by Subject             0             0             0             0             1             0             0             0
Adverse Event             0             0             1             0             1             0             0             0
[1]
Number of participants to start this period may include participants that did not complete treatment period.
Arm/Group Title Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W Total
Hide Arm/Group Description Participants were randomized to receive vupanorsen (PF-07285557) matched placebo SC injection. Single or double administration was given at every 2 or 4 weeks (Q2W or Q4W) to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Total of all reporting groups
Overall Number of Baseline Participants 44 23 24 23 45 45 46 36 286
Hide Baseline Analysis Population Description
Baseline analysis population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 44 participants 23 participants 24 participants 23 participants 45 participants 45 participants 46 participants 36 participants 286 participants
64.23  (8.09) 65.78  (7.27) 64.21  (9.92) 61.04  (9.31) 63.38  (8.41) 63.09  (8.80) 62.74  (8.64) 64.47  (7.74) 63.57  (8.48)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 23 participants 24 participants 23 participants 45 participants 45 participants 46 participants 36 participants 286 participants
Female
17
  38.6%
13
  56.5%
7
  29.2%
9
  39.1%
24
  53.3%
17
  37.8%
20
  43.5%
19
  52.8%
126
  44.1%
Male
27
  61.4%
10
  43.5%
17
  70.8%
14
  60.9%
21
  46.7%
28
  62.2%
26
  56.5%
17
  47.2%
160
  55.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 23 participants 24 participants 23 participants 45 participants 45 participants 46 participants 36 participants 286 participants
Hispanic or Latino
5
  11.4%
2
   8.7%
1
   4.2%
6
  26.1%
4
   8.9%
6
  13.3%
2
   4.3%
1
   2.8%
27
   9.4%
Not Hispanic or Latino
39
  88.6%
21
  91.3%
23
  95.8%
17
  73.9%
41
  91.1%
39
  86.7%
44
  95.7%
35
  97.2%
259
  90.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 23 participants 24 participants 23 participants 45 participants 45 participants 46 participants 36 participants 286 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
4
   9.1%
2
   8.7%
2
   8.3%
1
   4.3%
3
   6.7%
0
   0.0%
4
   8.7%
4
  11.1%
20
   7.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   4.3%
1
   4.2%
0
   0.0%
4
   8.9%
1
   2.2%
4
   8.7%
1
   2.8%
12
   4.2%
White
38
  86.4%
20
  87.0%
21
  87.5%
21
  91.3%
38
  84.4%
44
  97.8%
37
  80.4%
31
  86.1%
250
  87.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   4.5%
0
   0.0%
0
   0.0%
1
   4.3%
0
   0.0%
0
   0.0%
1
   2.2%
0
   0.0%
4
   1.4%
1.Primary Outcome
Title Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24
Hide Description Fasting was required at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set primary (FAS_primary) included all participants randomized to study intervention and who took at least 1 dose of study intervention, had a baseline measurement and at least one post-baseline measurement with all observations that occurred after discontinuation of treatment or after initiation of severe hypertriglyceridemia excluded.
Arm/Group Title Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
Hide Arm/Group Description:
Participants were randomized to receive vupanorsen (PF-07285557) matched placebo SC injection. Single or double administration was given at every 2 or 4 weeks (Q2W or Q4W) to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Overall Number of Participants Analyzed 44 23 23 23 42 45 46 35
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-1.1  (2.76) -23.5  (4.08) -23.2  (4.02) -25.3  (4.23) -28.8  (3.02) -27.8  (2.88) -25.8  (2.84) -27.6  (3.57)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 80 mg Q4W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter Least Square (LS) Mean difference
Estimated Value -22.4
Confidence Interval (2-Sided) 95%
-32.1 to -12.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.93
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 60 mg Q2W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -22.0
Confidence Interval (2-Sided) 95%
-31.7 to -12.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 120 mg Q4W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -24.1
Confidence Interval (2-Sided) 95%
-34.1 to -14.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 80 mg Q2W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -27.7
Confidence Interval (2-Sided) 95%
-35.7 to -19.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 160 mg Q4W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -26.6
Confidence Interval (2-Sided) 95%
-34.5 to -18.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.98
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 120 mg Q2W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -24.7
Confidence Interval (2-Sided) 95%
-32.5 to -16.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 160 mg Q2W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -26.5
Confidence Interval (2-Sided) 95%
-35.4 to -17.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.51
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline in Triglyceride (TG), Apolipoprotein B (ApoB), Low-Density Lipoprotein-Cholesterol (LDL-C), and Non-HDL-C at Week 16
Hide Description Blood samples were collected from participants in a fasted state for the measurement of TG, ApoB, HDL-C and LDL-C. Fasting was required at least 10 hours before blood sample collection. Non-HDL-C was calculated as total cholesterol minus HDL cholesterol. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants randomized to study intervention and who took at least 1 dose of study intervention and had a baseline measurement and at least one post-baseline measurement. Here, "Number Analyzed" signifies participants evaluable for specific rows.
Arm/Group Title Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
Hide Arm/Group Description:
Participants were randomized to receive vupanorsen (PF-07285557) matched placebo SC injection. Single or double administration was given at every 2 or 4 weeks (Q2W or Q4W) to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Overall Number of Participants Analyzed 44 23 24 23 43 45 46 36
Mean (Standard Deviation)
Unit of Measure: Percent change
TG Number Analyzed 43 participants 22 participants 23 participants 21 participants 40 participants 43 participants 44 participants 35 participants
-2.53  (31.247) -42.17  (28.081) -44.71  (22.725) -39.57  (32.546) -49.21  (21.049) -40.33  (21.311) -50.55  (20.234) -55.76  (14.625)
ApoB Number Analyzed 41 participants 21 participants 22 participants 22 participants 40 participants 44 participants 43 participants 34 participants
0.66  (20.372) -12.12  (15.839) -12.30  (12.604) -10.41  (17.067) -10.40  (14.690) -10.42  (19.332) -11.74  (15.560) -6.76  (18.890)
LDL-C Number Analyzed 41 participants 22 participants 22 participants 20 participants 40 participants 42 participants 44 participants 35 participants
-1.42  (24.092) -10.40  (31.199) -12.61  (21.904) -2.09  (26.921) -11.38  (22.001) -10.88  (26.640) -13.78  (19.861) -6.30  (29.825)
Non-HDL-C Number Analyzed 43 participants 22 participants 23 participants 21 participants 40 participants 43 participants 44 participants 35 participants
-3.25  (21.631) -21.65  (24.347) -24.71  (16.678) -20.06  (16.698) -24.79  (18.266) -21.68  (23.898) -27.23  (12.799) -22.44  (24.145)
3.Secondary Outcome
Title Percent Change From Baseline in TG, ApoB, and LDL-C at Week 24
Hide Description Fasting was required for all lipid measures at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS_primary included all participants randomized to study intervention and who took at least 1 dose of study intervention, had a baseline measurement and at least one post-baseline measurement with all observations that occurred after discontinuation of treatment or after initiation of severe hypertriglyceridemia excluded. Here, "Number Analyzed" signifies participants evaluable for specific rows.
Arm/Group Title Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
Hide Arm/Group Description:
Participants were randomized to receive vupanorsen (PF-07285557) matched placebo SC injection. Single or double administration was given at every 2 or 4 weeks (Q2W or Q4W) to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Overall Number of Participants Analyzed 44 23 23 23 42 45 46 35
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
TG Number Analyzed 44 participants 23 participants 23 participants 23 participants 42 participants 45 participants 46 participants 35 participants
-1.8  (3.71) -45.8  (5.53) -45.6  (5.50) -43.1  (5.76) -52.3  (4.10) -47.7  (3.90) -52.5  (3.85) -58.6  (4.90)
ApoB Number Analyzed 42 participants 22 participants 22 participants 23 participants 41 participants 45 participants 44 participants 35 participants
0.3  (2.46) -14.8  (3.60) -10.3  (3.57) -11.2  (3.76) -12.2  (2.68) -12.2  (2.55) -5.6  (2.57) -8.1  (3.17)
LDL-C Number Analyzed 43 participants 23 participants 22 participants 22 participants 42 participants 43 participants 46 participants 35 participants
-1.2  (3.69) -11.2  (5.41) -9.1  (5.52) -12.7  (5.63) -17.3  (4.00) -15.7  (3.92) -9.1  (3.77) -10.2  (4.74)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 80 mg Q4W
Comments TG
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -44.0
Confidence Interval (2-Sided) 95%
-57.1 to -30.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 60 mg Q2W
Comments TG
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -43.8
Confidence Interval (2-Sided) 95%
-56.9 to -30.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 120 mg Q4W
Comments TG
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -41.3
Confidence Interval (2-Sided) 95%
-54.8 to -27.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.85
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 80 mg Q2W
Comments TG
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -50.5
Confidence Interval (2-Sided) 95%
-61.4 to -39.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 160 mg Q4W
Comments TG
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -45.9
Confidence Interval (2-Sided) 95%
-56.5 to -35.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 120 mg Q2W
Comments TG
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -50.7
Confidence Interval (2-Sided) 95%
-61.2 to -40.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 160 mg Q2W
Comments TG
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -56.8
Confidence Interval (2-Sided) 95%
-68.9 to -44.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 80 mg Q4W
Comments ApoB
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -15.1
Confidence Interval (2-Sided) 95%
-23.7 to -6.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.36
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 60 mg Q2W
Comments ApoB
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -10.6
Confidence Interval (2-Sided) 95%
-19.2 to -2.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 120 mg Q4W
Comments ApoB
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -11.5
Confidence Interval (2-Sided) 95%
-20.3 to -2.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.49
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 80 mg Q2W
Comments ApoB
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -12.5
Confidence Interval (2-Sided) 95%
-19.7 to -5.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 160 mg Q4W
Comments ApoB
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -12.6
Confidence Interval (2-Sided) 95%
-19.5 to -5.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 120 mg Q2W
Comments ApoB
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.095
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -6.0
Confidence Interval (2-Sided) 95%
-13.0 to 1.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.56
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 160 mg Q2W
Comments ApoB
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -8.5
Confidence Interval (2-Sided) 95%
-16.4 to -0.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 80 mg Q4W
Comments LDL-C
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.129
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -10.0
Confidence Interval (2-Sided) 95%
-22.9 to 2.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.55
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 60 mg Q2W
Comments LDL-C
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.238
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -7.9
Confidence Interval (2-Sided) 95%
-21.0 to 5.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.65
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 120 mg Q4W
Comments LDL-C
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.090
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -11.4
Confidence Interval (2-Sided) 95%
-24.7 to 1.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 80 mg Q2W
Comments LDL-C
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -16.0
Confidence Interval (2-Sided) 95%
-26.7 to -5.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.44
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 160 mg Q4W
Comments LDL-C
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -14.5
Confidence Interval (2-Sided) 95%
-25.1 to -3.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 120 mg Q2W
Comments LDL-C
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.136
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -7.9
Confidence Interval (2-Sided) 95%
-18.3 to 2.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.28
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 160 mg Q2W
Comments LDL-C
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.138
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -9.0
Confidence Interval (2-Sided) 95%
-20.8 to 2.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.01
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 16
Hide Description ANGPTL3 is a protein primarily synthesized and secreted by the liver and is a member of the angiopoietin-like family of proteins. Blood samples were collected from participants in a fasted state for the measurement of ANGPTL3. Fasting was required at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants randomized to study intervention and who took at least 1 dose of study intervention and had a baseline measurement and at least one post-baseline measurement. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Arm/Group Title Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
Hide Arm/Group Description:
Participants were randomized to receive vupanorsen (PF-07285557) matched placebo SC injection. Single or double administration was given at every 2 or 4 weeks (Q2W or Q4W) to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Overall Number of Participants Analyzed 41 21 21 21 39 44 41 32
Mean (Standard Deviation)
Unit of Measure: Percent change
9.14  (36.729) -51.12  (30.444) -63.61  (16.934) -58.19  (22.175) -65.56  (21.908) -60.35  (21.040) -77.55  (15.469) -75.14  (23.549)
5.Secondary Outcome
Title Percent Change From Baseline in ANGPTL3 at Week 24
Hide Description ANGPTL3 is a protein primarily synthesized and secreted by the liver and is a member of the angiopoietin-like family of proteins. Blood samples were collected from participants in a fasted state for the measurement of ANGPTL3. Fasting was required at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS_primary included all participants randomized to study intervention and who took at least 1 dose of study intervention, had a baseline measurement and at least one post-baseline measurement with all observations that occurred after discontinuation of treatment or after initiation of severe hypertriglyceridemia excluded. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Arm/Group Title Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
Hide Arm/Group Description:
Participants were randomized to receive vupanorsen (PF-07285557) matched placebo SC injection. Single or double administration was given at every 2 or 4 weeks (Q2W or Q4W) to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
Overall Number of Participants Analyzed 42 22 21 22 40 45 42 33
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
13.3  (3.36) -56.6  (4.92) -66.3  (5.01) -63.8  (5.22) -73.0  (3.76) -67.1  (3.46) -78.9  (3.58) -81.9  (4.48)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 80 mg Q4W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -69.9
Confidence Interval (2-Sided) 95%
-81.6 to -58.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.97
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 60 mg Q2W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -79.6
Confidence Interval (2-Sided) 95%
-91.5 to -67.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 120 mg Q4W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -77.1
Confidence Interval (2-Sided) 95%
-89.4 to -64.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 80 mg Q2W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -86.3
Confidence Interval (2-Sided) 95%
-96.2 to -76.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 160 mg Q4W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -80.4
Confidence Interval (2-Sided) 95%
-89.9 to -70.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 120 mg Q2W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -92.2
Confidence Interval (2-Sided) 95%
-101.9 to -82.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Vupanorsen: 160 mg Q2W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -95.2
Confidence Interval (2-Sided) 95%
-106.2 to -84.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.59
Estimation Comments [Not Specified]
Time Frame From start of study intervention up to 12 weeks after last dose of study intervention (maximum for 36 weeks)
Adverse Event Reporting Description Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
 
Arm/Group Title Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
Hide Arm/Group Description Participants were randomized to receive vupanorsen (PF-07285557) matched placebo SC injection. Single or double administration was given at every 2 or 4 weeks (Q2W or Q4W) to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention. Participants were randomized to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the participant. Treatment duration was up to 24 weeks. Participants were followed up to 12 weeks after last dose of study intervention.
All-Cause Mortality
Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/44 (0.00%)   0/23 (0.00%)   0/24 (0.00%)   0/23 (0.00%)   0/45 (0.00%)   0/45 (0.00%)   0/46 (0.00%)   0/36 (0.00%) 
Hide Serious Adverse Events
Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/44 (9.09%)   2/23 (8.70%)   2/24 (8.33%)   0/23 (0.00%)   6/45 (13.33%)   1/45 (2.22%)   3/46 (6.52%)   1/36 (2.78%) 
Cardiac disorders                 
Acute coronary syndrome * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Acute myocardial infarction * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Atrial fibrillation * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
General disorders                 
Chest pain * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Hepatobiliary disorders                 
Cholangitis * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Infections and infestations                 
Gastroenteritis * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Urinary tract infection * 1  1/44 (2.27%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Investigations                 
SARS-CoV-2 test positive * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Metabolism and nutrition disorders                 
Dehydration * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Back pain * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Osteoarthritis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Spinal stenosis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Acoustic neuroma * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Basal cell carcinoma * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Bladder cancer * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Nervous system disorders                 
Ischaemic stroke * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Seizure * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Psychiatric disorders                 
Depression * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Vascular disorders                 
Thrombosis * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
1
Term from vocabulary, MedDRA v24.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   31/44 (70.45%)   15/23 (65.22%)   17/24 (70.83%)   12/23 (52.17%)   30/45 (66.67%)   28/45 (62.22%)   29/46 (63.04%)   31/36 (86.11%) 
Blood and lymphatic system disorders                 
Anaemia * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Eosinophilia * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Cardiac disorders                 
Atrial fibrillation * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Brugada syndrome * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Myocardial injury * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Palpitations * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  2/45 (4.44%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Sinus tachycardia * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Ear and labyrinth disorders                 
Ear pain * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Vertigo * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Eye disorders                 
Cataract * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Conjunctivitis allergic * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Ulcerative keratitis * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Vitreous floaters * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Gastrointestinal disorders                 
Abdominal discomfort * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Abdominal distension * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Abdominal pain * 1  1/44 (2.27%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Abdominal pain upper * 1  2/44 (4.55%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Acid peptic disease * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Constipation * 1  1/44 (2.27%)  1/23 (4.35%)  0/24 (0.00%)  1/23 (4.35%)  1/45 (2.22%)  1/45 (2.22%)  1/46 (2.17%)  1/36 (2.78%) 
Crohn's disease * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Dental necrosis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Diarrhoea * 1  3/44 (6.82%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  1/45 (2.22%)  2/46 (4.35%)  2/36 (5.56%) 
Diverticulum * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Dyspepsia * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  1/36 (2.78%) 
Faeces soft * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Gastrooesophageal reflux disease * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  2/45 (4.44%)  0/46 (0.00%)  2/36 (5.56%) 
Haematochezia * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Nausea * 1  2/44 (4.55%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  2/45 (4.44%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Oesophageal pain * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Rectal haemorrhage * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Toothache * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  2/46 (4.35%)  0/36 (0.00%) 
Vomiting * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
General disorders                 
Asthenia * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Chest discomfort * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Chest pain * 1  1/44 (2.27%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Chills * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Fatigue * 1  2/44 (4.55%)  1/23 (4.35%)  1/24 (4.17%)  0/23 (0.00%)  1/45 (2.22%)  2/45 (4.44%)  3/46 (6.52%)  0/36 (0.00%) 
Hunger * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Injection site bruising * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  1/46 (2.17%)  1/36 (2.78%) 
Injection site dermatitis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  1/36 (2.78%) 
Injection site erythema * 1  0/44 (0.00%)  1/23 (4.35%)  1/24 (4.17%)  2/23 (8.70%)  2/45 (4.44%)  1/45 (2.22%)  3/46 (6.52%)  4/36 (11.11%) 
Injection site pain * 1  1/44 (2.27%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Injection site rash * 1  0/44 (0.00%)  1/23 (4.35%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Injection site reaction * 1  0/44 (0.00%)  1/23 (4.35%)  3/24 (12.50%)  4/23 (17.39%)  4/45 (8.89%)  4/45 (8.89%)  6/46 (13.04%)  8/36 (22.22%) 
Injection site recall reaction * 1  0/44 (0.00%)  0/23 (0.00%)  2/24 (8.33%)  1/23 (4.35%)  2/45 (4.44%)  0/45 (0.00%)  5/46 (10.87%)  3/36 (8.33%) 
Injection site vesicles * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Malaise * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Non-cardiac chest pain * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Oedema peripheral * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  2/45 (4.44%)  1/45 (2.22%)  1/46 (2.17%)  0/36 (0.00%) 
Pain * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Peripheral swelling * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  2/45 (4.44%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Pyrexia * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  2/45 (4.44%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Therapeutic response unexpected * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Thirst * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Vessel puncture site bruise * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Hepatobiliary disorders                 
Cholelithiasis * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Drug-induced liver injury * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  3/46 (6.52%)  0/36 (0.00%) 
Hepatic steatosis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Nonalcoholic fatty liver disease * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Immune system disorders                 
Hypersensitivity * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Seasonal allergy * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Infections and infestations                 
Acute sinusitis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Bronchitis * 1  2/44 (4.55%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  2/45 (4.44%)  0/46 (0.00%)  1/36 (2.78%) 
COVID-19 * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Cellulitis * 1  2/44 (4.55%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Conjunctivitis * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Cystitis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Fungal infection * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Fungal skin infection * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Gastroenteritis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Gastroenteritis viral * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Gastrointestinal bacterial infection * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Helicobacter infection * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Herpes zoster * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Infection parasitic * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Injection site cellulitis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Kidney infection * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Nasopharyngitis * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Oral candidiasis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Otitis externa * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Pharyngitis * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Sinusitis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Tinea cruris * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Tooth abscess * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Tooth infection * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  2/46 (4.35%)  0/36 (0.00%) 
Upper respiratory tract infection * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Urinary tract infection * 1  3/44 (6.82%)  1/23 (4.35%)  1/24 (4.17%)  1/23 (4.35%)  3/45 (6.67%)  1/45 (2.22%)  1/46 (2.17%)  3/36 (8.33%) 
Viral infection * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Vulvovaginal candidiasis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Vulvovaginal mycotic infection * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Injury, poisoning and procedural complications                 
Animal bite * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Arthropod bite * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Back injury * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Epicondylitis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Fall * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  1/23 (4.35%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Foot fracture * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Head injury * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Injection related reaction * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Ligament sprain * 1  1/44 (2.27%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Muscle rupture * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Post procedural discomfort * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Procedural pain * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Skin abrasion * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Vaccination complication * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Investigations                 
Activated partial thromboplastin time prolonged * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Alanine aminotransferase abnormal * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Alanine aminotransferase increased * 1  2/44 (4.55%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  1/45 (2.22%)  4/46 (8.70%)  9/36 (25.00%) 
Albumin urine present * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Aspartate aminotransferase increased * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  2/46 (4.35%)  4/36 (11.11%) 
Blood calcium increased * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Blood glucose increased * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Blood potassium abnormal * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Blood pressure decreased * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Blood pressure increased * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Body temperature increased * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Creatinine renal clearance abnormal * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Electrocardiogram QRS complex prolonged * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Electrocardiogram QT prolonged * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Electrocardiogram abnormal * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Haematocrit increased * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Hepatic enzyme increased * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  2/46 (4.35%)  3/36 (8.33%) 
Liver function test abnormal * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Liver function test increased * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Magnetic resonance imaging spinal abnormal * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Mean cell haemoglobin concentration decreased * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Mean cell volume increased * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Urine albumin/creatinine ratio abnormal * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Urine albumin/creatinine ratio increased * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Urine analysis abnormal * 1  0/44 (0.00%)  0/23 (0.00%)  2/24 (8.33%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Weight decreased * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Transaminases increased * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  2/45 (4.44%)  0/45 (0.00%)  1/46 (2.17%)  6/36 (16.67%) 
Metabolism and nutrition disorders                 
Decreased appetite * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Dehydration * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Diabetes mellitus * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Diabetes mellitus inadequate control * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Glucose tolerance impaired * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Gout * 1  1/44 (2.27%)  0/23 (0.00%)  2/24 (8.33%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Hyperglycaemia * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Hyperkalaemia * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Hypoglycaemia * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Hypokalaemia * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Increased appetite * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Type 2 diabetes mellitus * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  1/45 (2.22%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia * 1  2/44 (4.55%)  1/23 (4.35%)  1/24 (4.17%)  0/23 (0.00%)  4/45 (8.89%)  1/45 (2.22%)  3/46 (6.52%)  1/36 (2.78%) 
Arthritis * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Bone cyst * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Bursitis * 1  1/44 (2.27%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Flank pain * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  2/36 (5.56%) 
Intervertebral disc degeneration * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Intervertebral disc disorder * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Joint stiffness * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Joint swelling * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Muscle fatigue * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Muscle spasms * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Muscular weakness * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  3/36 (8.33%) 
Musculoskeletal chest pain * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Musculoskeletal pain * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Myalgia * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  2/45 (4.44%)  3/45 (6.67%)  0/46 (0.00%)  0/36 (0.00%) 
Neck pain * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  1/46 (2.17%)  0/36 (0.00%) 
Osteoarthritis * 1  0/44 (0.00%)  0/23 (0.00%)  2/24 (8.33%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Pain in extremity * 1  1/44 (2.27%)  0/23 (0.00%)  3/24 (12.50%)  0/23 (0.00%)  3/45 (6.67%)  0/45 (0.00%)  2/46 (4.35%)  0/36 (0.00%) 
Plantar fascial fibromatosis * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Rotator cuff syndrome * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Scoliosis * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Spinal pain * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Temporomandibular joint syndrome * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Tendonitis * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Tenosynovitis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Back pain * 1  2/44 (4.55%)  0/23 (0.00%)  2/24 (8.33%)  0/23 (0.00%)  6/45 (13.33%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Basal cell carcinoma * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Nervous system disorders                 
Balance disorder * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Carpal tunnel syndrome * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Dizziness * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  2/45 (4.44%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Headache * 1  2/44 (4.55%)  1/23 (4.35%)  1/24 (4.17%)  1/23 (4.35%)  2/45 (4.44%)  3/45 (6.67%)  1/46 (2.17%)  0/36 (0.00%) 
Hypoaesthesia * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Migraine * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Neuropathy peripheral * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  1/46 (2.17%)  0/36 (0.00%) 
Paraesthesia * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  2/45 (4.44%)  0/46 (0.00%)  0/36 (0.00%) 
Radiculopathy * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Sciatica * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Sensory disturbance * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Transient ischaemic attack * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Psychiatric disorders                 
Adjustment disorder * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Anxiety * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  2/23 (8.70%)  1/45 (2.22%)  2/45 (4.44%)  0/46 (0.00%)  0/36 (0.00%) 
Depression * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Insomnia * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Major depression * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Renal and urinary disorders                 
Acute kidney injury * 1  0/44 (0.00%)  0/23 (0.00%)  2/24 (8.33%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Calculus bladder * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Chronic kidney disease * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Dysuria * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Haematuria * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Microalbuminuria * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Nephrolithiasis * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Pollakiuria * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Proteinuria * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  2/45 (4.44%)  0/46 (0.00%)  0/36 (0.00%) 
Renal cyst * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Renal failure * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Urge incontinence * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Urinary incontinence * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Reproductive system and breast disorders                 
Abnormal uterine bleeding * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Atrophic vulvovaginitis * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Erectile dysfunction * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Genital atrophy * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Prostatitis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Vulvovaginal dryness * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Cough * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Dyspnoea * 1  2/44 (4.55%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Epistaxis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Haemoptysis * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Nasal congestion * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Productive cough * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Pulmonary mass * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Rhinitis allergic * 1  2/44 (4.55%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Sinus pain * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Sputum increased * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Skin and subcutaneous tissue disorders                 
Actinic keratosis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Alopecia * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Dermatitis * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Dermatitis allergic * 1  2/44 (4.55%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
Dermatitis contact * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Erythema * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  1/45 (2.22%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Hyperhidrosis * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Miliaria * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Petechiae * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Pruritus * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  1/45 (2.22%)  0/45 (0.00%)  1/46 (2.17%)  1/36 (2.78%) 
Rash * 1  0/44 (0.00%)  1/23 (4.35%)  0/24 (0.00%)  0/23 (0.00%)  2/45 (4.44%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Rosacea * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Skin discolouration * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  1/46 (2.17%)  0/36 (0.00%) 
Skin lesion * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  2/45 (4.44%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Skin mass * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Vascular disorders                 
Deep vein thrombosis * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  1/36 (2.78%) 
Hot flush * 1  1/44 (2.27%)  0/23 (0.00%)  0/24 (0.00%)  1/23 (4.35%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Hypertension * 1  3/44 (6.82%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  3/36 (8.33%) 
Hypotension * 1  0/44 (0.00%)  0/23 (0.00%)  1/24 (4.17%)  0/23 (0.00%)  0/45 (0.00%)  0/45 (0.00%)  0/46 (0.00%)  0/36 (0.00%) 
Peripheral coldness * 1  0/44 (0.00%)  0/23 (0.00%)  0/24 (0.00%)  0/23 (0.00%)  0/45 (0.00%)  1/45 (2.22%)  0/46 (0.00%)  0/36 (0.00%) 
1
Term from vocabulary, MedDRA v24.1
*
Indicates events were collected by non-systematic assessment
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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04516291    
Other Study ID Numbers: C4491011
2020-002796-35 ( EudraCT Number )
First Submitted: August 13, 2020
First Posted: August 18, 2020
Results First Submitted: September 6, 2022
Results First Posted: October 4, 2022
Last Update Posted: October 4, 2022