Trial Outcomes & Findings for Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension (NCT NCT00380068)
NCT ID: NCT00380068
Last Updated: 2012-04-05
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
224 participants
Primary outcome timeframe
Baseline to Week 24
Results posted on
2012-04-05
Participant Flow
Enrollment occurred between September 2006 and January 2008 and the study was conducted between August 2006 and May 2009 in 39 centers in the United States, Australia and Canada
The screening period was 4 weeks. Participants who received bosentan or sitaxsentan within 4 weeks prior to the screening visit were excluded.
Participant milestones
| Measure |
Ambrisentan
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Overall Study
STARTED
|
224
|
|
Overall Study
COMPLETED
|
155
|
|
Overall Study
NOT COMPLETED
|
69
|
Reasons for withdrawal
| Measure |
Ambrisentan
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Overall Study
Adverse Event
|
40
|
|
Overall Study
Withdrawal by Subject
|
10
|
|
Overall Study
Not compliant
|
6
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Addition of other PAH therapeutic agent
|
1
|
|
Overall Study
Lung transplant
|
3
|
|
Overall Study
Physician Decision
|
2
|
|
Overall Study
Partipant moved away
|
1
|
|
Overall Study
Lack of Efficacy
|
5
|
Baseline Characteristics
Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension
Baseline characteristics by cohort
| Measure |
Ambrisentan
n=224 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
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|---|---|
|
Age Continuous
|
55 years
STANDARD_DEVIATION 16 • n=5 Participants
|
|
Sex: Female, Male
Female
|
156 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
68 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set. Last Observation Carried forward. 4 participants were excluded from the analysis due to lack of post-baseline 6MWD data.
Outcome measures
| Measure |
Ambrisentan
n=220 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Change From Baseline to Week 24 in 6 Minute Walk Distance (6MWD)
|
20.5 meters
Standard Deviation 65.64 • Interval 21.0 to 48.0
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set. Last Observation Carried forward. 4 participants were excluded from the analysis due to lack of post-baseline Borg Dyspnea Index data.
Change from Baseline to Week 24 in Borg Dyspnea Index. The Borg Dyspnea Index of Perceived Exertion Scores range from 0 to 10. Best and Worst values are: 0 (Best) to 10 (Worst). Scales are described as rating of breathlessness and its description: 0= none; 0.5= very,very slight (just noticeable); 1= very slight; 2=slight; 3= moderate; 4= somewhat severe; 5= severe; 6 (in between severe and very severe); 7= very severe; 8 (in between very, very severe and maximum); 9= very, very severe; and 10= maximum.
Outcome measures
| Measure |
Ambrisentan
n=220 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Change From Baseline to Week 24 in Borg Dyspnea Index
|
-0.5 Units on a scale
Standard Deviation 2.18 • Interval -0.8 to -0.3
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Full Analysis Set. Observed data. 114 participants were excluded from the analysis due to lack of Week 48 Borg Dyspnea Index data.
Change from Baseline to Week 48 in Borg Dyspnea Index. The Borg Dyspnea Index of Perceived Exertion Scores range from 0 to 10. Best and Worst values are: 0 (Best) to 10 (Worst). Scales are described as rating of breathlessness and its description: 0= none; 0.5= very,very slight (just noticeable); 1= very slight; 2=slight; 3= moderate; 4= somewhat severe; 5= severe; 6 (in between severe and very severe); 7= very severe; 8 (in between very, very severe and maximum); 9= very, very severe; and 10= maximum.
Outcome measures
| Measure |
Ambrisentan
n=110 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Change From Baseline to Week 48 in Borg Dyspnea Index
|
-0.6 Units on a scale
Standard Deviation 1.91 • Interval -1.0 to -0.2
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set. Last Observation Carried forward. 10 participants were excluded from the analysis due to lack of baseline or post-baseline BNP data.
Outcome measures
| Measure |
Ambrisentan
n=214 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Percent Change From Baseline to Week 24 in B-type Natriuretic Peptide (BNP)
|
-25.5 Percent change in BNP
Interval -33.6 to -16.3
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Full Analysis Set. Observed data. 111 participants were excluded from the analysis due to lack of baseline or Week 48 BNP data.
Outcome measures
| Measure |
Ambrisentan
n=112 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Percent Change From Baseline to Week 48 in BNP
|
-29.2 Percent change in BNP
Interval -39.8 to -16.6
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set. Last Observation Carried Forward. 3 participants were not analyzed due to lack of post-baseline WHO functional class data.
Change from baseline in World Health Organization functional class (WHO) at Week 24 is the incidence of participants that improved, had no change, or worsened. WHO categories are 1 to 4 with the worse category at 4. Improvement = a category change from baseline of \<= -1: change of -3 (eg, WHO from 4 to 1), change of -2 (eg, WHO from 3 to 1), change of -1 (eg, WHO from 2 to 1). Inversely, participants worsening are those with a category change from baseline of at least +1. No change in WHO functional class represents the percentage of participants with a change in category from baseline of 0.
Outcome measures
| Measure |
Ambrisentan
n=221 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Change From Baseline to Week 24 in WHO Functional Class
-3
|
0 Percentage of participants
|
|
Change From Baseline to Week 24 in WHO Functional Class
-2
|
0.9 Percentage of participants
|
|
Change From Baseline to Week 24 in WHO Functional Class
-1
|
22.2 Percentage of participants
|
|
Change From Baseline to Week 24 in WHO Functional Class
0
|
70.1 Percentage of participants
|
|
Change From Baseline to Week 24 in WHO Functional Class
1
|
6.8 Percentage of participants
|
|
Change From Baseline to Week 24 in WHO Functional Class
2
|
0 Percentage of participants
|
|
Change From Baseline to Week 24 in WHO Functional Class
3
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Full Analysis Set. Observed Data. 3 participants were not analyzed due to lack of post-baseline WHO functional class data.
Change from baseline in WHO at Week 48 is expressed as the incidence of participants that improved, had no change or worsened. WHO categories range from 1 to 4 with the worse category at 4. Improvement = a category change from baseline of \<= -1: change of -3 (eg, WHO from 4 to 1), change of -2 (eg, WHO from 3 to 1), change of -1 (eg, WHO from 2 to 1). Inversely, participants worsening are those with a category change from baseline of at least +1. No change in WHO functional class represents the percentage of participants with a change in category from baseline of 0.
Outcome measures
| Measure |
Ambrisentan
n=119 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Change From Baseline to Week 48 in WHO Functional Class
-3
|
0 Percentage of participants
|
|
Change From Baseline to Week 48 in WHO Functional Class
-2
|
1.7 Percentage of participants
|
|
Change From Baseline to Week 48 in WHO Functional Class
-1
|
34.5 Percentage of participants
|
|
Change From Baseline to Week 48 in WHO Functional Class
0
|
57.1 Percentage of participants
|
|
Change From Baseline to Week 48 in WHO Functional Class
1
|
6.7 Percentage of participants
|
|
Change From Baseline to Week 48 in WHO Functional Class
2
|
0 Percentage of participants
|
|
Change From Baseline to Week 48 in WHO Functional Class
3
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set. Last Observation Carried forward. 26 participants were excluded from the analysis due to lack of baseline or post-baseline SF-36 data.
Change from baseline to Week 24 in the SF-36 health survey physical functioning scale. 10 activities rated by health limitations using 3 categories (1= Yes, limited a lot; 2= Yes, limited a little; and 3= No, not limited at all). The best score is 3 and the worst score is 1. Scores are transformed by subtracting the unit by the lowest raw score and dividing by the raw score range. The scores are then standardized with the 1998 General United States (US) population mean and standard deviation (SD). Finally, the scores are transformed to the norm-based scoring with a mean of 50 and SD of 10.
Outcome measures
| Measure |
Ambrisentan
n=198 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Change From Baseline to Week 24 in SF-36 Health Survey Physical Functioning Scale
|
2.88 Units on a scale
Standard Deviation 7.943 • Interval -29.5 to 25.3
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Full Analysis Set. Last Observation Carried forward. 25 participants were excluded from the analysis due to lack of baseline or post-baseline SF-36 data.
Change from baseline to Week 48 in the SF-36 health survey physical functioning scale. 10 activities are rated by health limitations using 3 categories (1= Yes, limited a lot; 2= Yes, limited a little; and 3= No, not limited at all). The best score is 3 and the worst score is 1. Scores are transformed by subtracting the unit by the lowest raw score and dividing by the raw score range. The scores are then standardized with the 1998 General US population mean and standard deviation. Finally, the scores are transformed to the norm-based scoring with a mean of 50 and standard deviation of 10.
Outcome measures
| Measure |
Ambrisentan
n=199 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Change From Baseline to Week 48 in SF-36 Health Survey Physical Functioning Scale
|
2.80 Units on a scale
Standard Deviation 8.634
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full analysis set. Participants who were lost to follow-up were censored at the date of last contact.
Clinical worsening: occurrence of death, lung transplantation, hospitalization for PH, atrial septostomy, a change to chronic prostanoid or sildenafil treatment due to protocol-defined worsening criteria, or study withdrawal due to the addition of other clinically approved PH therapeutic agents
Outcome measures
| Measure |
Ambrisentan
n=224 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
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|---|---|
|
Percent of Participants With no Clinical Worsening of Pulmonary Hypertension (PH) at Week 24
|
89.4 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Full analysis set. Participants who were lost to follow-up were censored at the date of last contact.
Clinical worsening: occurrence of death, lung transplantation, hospitalization for PH, atrial septostomy, a change to chronic prostanoid or sildenafil treatment due to protocol-defined worsening criteria, or study withdrawal due to the addition of other clinically approved PH therapeutic agents
Outcome measures
| Measure |
Ambrisentan
n=224 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
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|---|---|
|
Percent of Participants With no Clinical Worsening of PH at Week 48
|
84.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set. Participants who were lost to follow-up were censored at the date of last contact.
Defined by occurrence of death, lung transplantation, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents
Outcome measures
| Measure |
Ambrisentan
n=224 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Failure-free Treatment Status
|
95.3 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Full Analysis Set. Participants who were lost to follow-up were censored at the date of last contact.
Defined by occurrence of death, lung transplantation, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents
Outcome measures
| Measure |
Ambrisentan
n=224 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Failure-free Treatment Status
|
92.9 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set - Subset of participants who were not receiving other PH therapy at baseline.
Defined by no addition of sildenafil, iloprost, treprostinil, or epoprostenol to ongoing ambrisentan treatment
Outcome measures
| Measure |
Ambrisentan
n=107 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Monotherapy Treatment Status
|
95.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Full Analysis Set - Subset of participants who were not receiving other PH therapy at baseline.
Defined by no addition of sildenafil, iloprost, treprostinil, or epoprostenol to ongoing ambrisentan treatment
Outcome measures
| Measure |
Ambrisentan
n=107 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Monotherapy Treatment Status
|
90.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set. Participants who were lost to follow-up were censored at the date of last contact.
Defined as not dying during study participation
Outcome measures
| Measure |
Ambrisentan
n=224 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Long-term Survival
|
97.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Full Analysis Set. Participants who were lost to follow-up were censored at the date of last contact.
Defined as not dying during study participation
Outcome measures
| Measure |
Ambrisentan
n=224 Participants
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Long-term Survival
|
95.3 Percentage of participants
|
Adverse Events
Ambrisentan
Serious events: 97 serious events
Other events: 203 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ambrisentan
n=224 participants at risk
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Investigations
alanine aminotransferase increased
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Investigations
aspartate aminotransferase increased
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
General disorders
drug interaction
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Investigations
international normalised ratio increased
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Musculoskeletal and connective tissue disorders
muscle tightness
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Injury, poisoning and procedural complications
narcotic intoxication
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Blood and lymphatic system disorders
neutropenia
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Gastrointestinal disorders
abdominal pain
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
abscess limb
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
atrial fibrillation
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
atrial flutter
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
atrioventricular block third degree
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Hepatobiliary disorders
autoimmune hepatitis
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Investigations
blood glucose increased
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
breast cancer
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
bronchiectasis
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
bronchitis
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
bronchitis acute
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
cardiac failure congestive
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
cardio-respiratory arrest
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
cellulitis
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
central line infection
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Nervous system disorders
cerebrovascular accident
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
General disorders
chest pain
|
2.2%
5/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
chronic obstructive pulmonary disease
|
3.1%
7/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Vascular disorders
deep vein thrombosis
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Metabolism and nutrition disorders
dehydration
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
device related infection
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Metabolism and nutrition disorders
diabetes mellitus inadequate control
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Nervous system disorders
dizziness
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
General disorders
drug hypersensitivity
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
dyspnoea
|
4.5%
10/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
endocarditis
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
enteritis infectious
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
enterobacter infection
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
General disorders
face oedema
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Injury, poisoning and procedural complications
femur fracture
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Metabolism and nutrition disorders
fluid overload
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
gastroenteritis viral
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Gastrointestinal disorders
gastrooesophageal reflux disease
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
haemoptysis
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Nervous system disorders
headache
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Metabolism and nutrition disorders
hypervolaemia
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Metabolism and nutrition disorders
hypoglycaemia
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Metabolism and nutrition disorders
hypokalaemia
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Metabolism and nutrition disorders
hyponatraemia
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
hypoventilation
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
hypoxia
|
1.8%
4/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
influenza
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
interstitial lung disease
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
left ventricular failure
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Investigations
liver function test abnormal
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
lower respiratory tract infection
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
lung neoplasm malignant
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Psychiatric disorders
mental status changes
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Nervous system disorders
migraine
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Nervous system disorders
migraine with aura
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Musculoskeletal and connective tissue disorders
muscular weakness
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
General disorders
non-cardiac chest pain
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
General disorders
oedema
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
General disorders
oedema peripheral
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Reproductive system and breast disorders
ovarian cyst ruptured
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
pericardial effusion
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
pleural effusion
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
pneumonia
|
6.7%
15/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
pneumonia bacterial
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
productive cough
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary embolism
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary fibrosis
|
1.8%
4/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary hypertension
|
3.6%
8/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
pulomonary oedema
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Vascular disorders
raynaud's phenomenon
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
recurrent cancer
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Renal and urinary disorders
renal failure
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Renal and urinary disorders
renal failure acute
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Renal and urinary disorders
renal impairment
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
respiratory failure
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
respiratory tract infection
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
right ventricular failure
|
7.1%
16/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
sedation
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
sepsis
|
1.8%
4/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Vascular disorders
shock haemorrhagic
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Congenital, familial and genetic disorders
sickle cell anaemia with crisis
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Injury, poisoning and procedural complications
spinal compression fracture
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Nervous system disorders
syncope
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Musculoskeletal and connective tissue disorders
systemic lupus erythematosus
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Investigations
transaminase increased
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
transitional cell carcinoma
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
tremor
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Renal and urinary disorders
urinary retention
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
urinary tract infection
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Reproductive system and breast disorders
vaginal haemorrhage
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Blood and lymphatic system disorders
anaemia
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Blood and lymphatic system disorders
iron deficiency anaemia
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Blood and lymphatic system disorders
thrombocytopenia
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
cardiac arrest
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
cardiac failure
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
cor pulmonale
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
palpitations
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
supraventricular tachycardia
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Gastrointestinal disorders
diverticular perforation
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Gastrointestinal disorders
gastrointestinal haemorrhage
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Gastrointestinal disorders
lower gastrointestinal haemorrhage
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Gastrointestinal disorders
peritonitis
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
appendicitis
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
arthritis infective
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
catheter sepsis
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
gastroenteritis
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
sepsis syndrome
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
septic shock
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
upper respiratory tract infection
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Injury, poisoning and procedural complications
accidental overdose
|
0.89%
2/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Injury, poisoning and procedural complications
fall
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Injury, poisoning and procedural complications
fibula fracture
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Injury, poisoning and procedural complications
thrombosis in device
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Injury, poisoning and procedural complications
tibia fracture
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Investigations
hepatic enzyme increased
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Metabolism and nutrition disorders
diabetes mellitus
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Metabolism and nutrition disorders
hyperkalaemia
|
1.3%
3/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Musculoskeletal and connective tissue disorders
fracture nonunion
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Musculoskeletal and connective tissue disorders
scleroderma
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Nervous system disorders
presyncope
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Nervous system disorders
subarachnoid haemorrhage
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Pregnancy, puerperium and perinatal conditions
pregnancy
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Psychiatric disorders
anxiety
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Psychiatric disorders
confusional state
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Psychiatric disorders
depression
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Psychiatric disorders
nervousness
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Psychiatric disorders
panic attack
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Psychiatric disorders
suicidal ideation
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Psychiatric disorders
suicide attempt
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Renal and urinary disorders
nephrolithiasis
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Renal and urinary disorders
renal failure chronic
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
acute respiratory failure
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
pleuritic pain
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
respiratory distress
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Skin and subcutaneous tissue disorders
skin ulcer
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Vascular disorders
hypotension
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Vascular disorders
vasculitis
|
0.45%
1/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
Other adverse events
| Measure |
Ambrisentan
n=224 participants at risk
Eligible participants received 5 mg ambrisentan once daily for the first 24 weeks. One dose reduction to 2.5 mg was permitted during the 24-week fixed-dose treatment period if the participant did not tolerate the study drug. After the initial 24-week treatment period, investigators could adjust the study drug dose as clinically indicated (available doses were 2.5, 5, and 10 mg).
|
|---|---|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
8.9%
20/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Musculoskeletal and connective tissue disorders
back pain
|
10.7%
24/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Investigations
brain natriuretic peptide increased
|
8.0%
18/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
12.9%
29/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Psychiatric disorders
depression
|
12.1%
27/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Gastrointestinal disorders
diarrhoea
|
9.8%
22/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Nervous system disorders
dizziness
|
13.4%
30/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
dyspnoea
|
21.4%
48/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
General disorders
fatigue
|
17.4%
39/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Vascular disorders
flushing
|
7.1%
16/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Nervous system disorders
headache
|
28.1%
63/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Metabolism and nutrition disorders
hypokalemia
|
8.5%
19/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Psychiatric disorders
insomnia
|
7.6%
17/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
nasal congestion
|
18.3%
41/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Gastrointestinal disorders
nausea
|
14.7%
33/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
General disorders
oedema peripheral
|
42.4%
95/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Musculoskeletal and connective tissue disorders
pain in extremity
|
10.7%
24/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
upper respiratory tract infection
|
24.1%
54/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
urinary tract infection
|
9.8%
22/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Gastrointestinal disorders
vomiting
|
8.0%
18/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Blood and lymphatic system disorders
anaemia
|
7.6%
17/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Cardiac disorders
palpitations
|
7.6%
17/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Gastrointestinal disorders
abdominal pain
|
5.4%
12/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Gastrointestinal disorders
constipation
|
8.5%
19/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
General disorders
chest pain
|
7.1%
16/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
General disorders
pyrexia
|
5.4%
12/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
bronchitis
|
7.6%
17/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
nasopharyngitis
|
5.4%
12/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Infections and infestations
sinusitis
|
7.6%
17/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Investigations
international normalised ratio increased
|
6.7%
15/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Metabolism and nutrition disorders
fluid overload
|
5.4%
12/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Psychiatric disorders
anxiety
|
5.4%
12/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
7.1%
16/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Skin and subcutaneous tissue disorders
rash
|
5.8%
13/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
|
Vascular disorders
hypotension
|
5.4%
12/224 • AEs were to be collected during study and up to 72 hours after last dose. SAEs, including deaths, that occurred during the study or within 4 weeks of receiving the last dose of study drug, whether or not related to study drug, were to be reported.
|
Additional Information
Martine Allard, PhD; Senior Clinical Research Scientist
Gilead Sciences Inc
Phone: 650-524-3898
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee PIs have right disclose data upon publication of a multi-center publication coordinated by Sponsor or 18 months after Study is completed at all sites if multi-center publication is not submitted by Sponsor within 12 mos. PI to furnish Sponsor with copy of proposed disclosure at least 90 days prior to proposed disclosure. Sponsor has right to ensure accuracy of disclosure and request deletion of confidential information. Sponsor may not make editorial changes to the results or conclusions.
- Publication restrictions are in place
Restriction type: OTHER