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TD-0903 for ALI Associated With COVID-19

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: NCT04402866
Recruitment Status : Completed
First Posted : May 27, 2020
Results First Posted : March 17, 2022
Last Update Posted : March 17, 2022
Sponsor:
Information provided by (Responsible Party):
Theravance Biopharma

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Acute Lung Injury (ALI) Associated With COVID-19
Lung Inflammation Associated With COVID-19
Interventions Drug: TD-0903
Drug: Placebo
Enrollment 235
Recruitment Details 235 participants were enrolled across 24 sites in the United States, Brazil, Finland, the Republic of Moldova, Romania, Ukraine and the United Kingdom.
Pre-assignment Details 235 participants were enrolled and 230 participants were randomized and treated with study drug. Within each cohort in Part 1 (multiple-ascending dose design), participants were randomized 3:1, TD-0903 to placebo. During Part 2 (parallel-group design), participants were stratified by baseline age (≤ 60 versus > 60 years), and by concurrent use of antiviral medications (yes or no) at baseline. Within each stratum, participants were randomized 1:1 to receive either TD-0903 or placebo.
Arm/Group Title Part 1: Matching Placebo Part 1: TD-0903 - 1 mg Part 1: TD-0903 - 3 mg Part 1: TD-0903 - 10 mg Part 2: Matching Placebo Part 2: TD-0903 - 3 mg
Hide Arm/Group Description Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 1 mg. Participants were administered a 2 mg loading dose as the total dose on Day 1. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 10 mg. Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.
Period Title: Overall Study
Started 6 6 7 6 104 106
Randomized and Treated With Study Drug 6 6 7 6 102 103
Completed 4 5 6 6 89 92
Not Completed 2 1 1 0 15 14
Reason Not Completed
Discontinued Prior to Treatment             0             0             0             0             2             3
Adverse Event             2             1             0             0             13             8
Miscellaneous             0             0             1             0             0             0
Lost to Follow-up             0             0             0             0             0             1
Withdrawal by Subject             0             0             0             0             0             2
Arm/Group Title Part 1: Matching Placebo Part 1: TD-0903 - 1 mg Part 1: TD-0903 - 3 mg Part 1: TD-0903 - 10 mg Part 2: Matching Placebo Part 2: TD-0903 - 3 mg Total
Hide Arm/Group Description Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 1 mg. Participants were administered a 2 mg loading dose as the total dose on Day 1. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 10 mg. Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1. Total of all reporting groups
Overall Number of Baseline Participants 6 6 7 6 104 106 235
Hide Baseline Analysis Population Description
Part 1: Safety analysis set - all participants who received at least one dose of study drug. Part 2: Intent-to-Treat (ITT) analysis set - all participants who were randomized into the study.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 7 participants 6 participants 104 participants 106 participants 235 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
3
  50.0%
3
  50.0%
5
  71.4%
5
  83.3%
70
  67.3%
60
  56.6%
146
  62.1%
>=65 years
3
  50.0%
3
  50.0%
2
  28.6%
1
  16.7%
34
  32.7%
46
  43.4%
89
  37.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 7 participants 6 participants 104 participants 106 participants 235 participants
Female
3
  50.0%
1
  16.7%
3
  42.9%
1
  16.7%
41
  39.4%
41
  38.7%
90
  38.3%
Male
3
  50.0%
5
  83.3%
4
  57.1%
5
  83.3%
63
  60.6%
65
  61.3%
145
  61.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 7 participants 6 participants 104 participants 106 participants 235 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
10
   9.6%
14
  13.2%
24
  10.2%
Not Hispanic or Latino
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
90
  86.5%
89
  84.0%
204
  86.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4
   3.8%
3
   2.8%
7
   3.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 7 participants 6 participants 104 participants 106 participants 235 participants
Asian
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.4%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   1.9%
2
   0.9%
White
5
  83.3%
6
 100.0%
7
 100.0%
6
 100.0%
102
  98.1%
104
  98.1%
230
  97.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.0%
0
   0.0%
1
   0.4%
Other
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.0%
0
   0.0%
1
   0.4%
1.Primary Outcome
Title Part 2: Number of Respiratory Failure-free Days (RFDs) From Randomization to Day 28
Hide Description

An RFD was defined as a day that a participant was alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) from randomization through Day 28. The number of RFDs was 0 for participants who used respiratory support for 28 days or longer or for participants who died on or before Day 28.

A clinical status score of ≤ 4 on a given day was equivalent to an RFD. The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. A clinical status score of 4 was defined as a participant who was hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19).

Time Frame Randomization to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.
Arm/Group Title Part 2: Matching Placebo Part 2: TD-0903 - 3 mg
Hide Arm/Group Description:
Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.
TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.
Overall Number of Participants Analyzed 102 100
Median (Inter-Quartile Range)
Unit of Measure: days
21.0
(15.0 to 23.0)
21.0
(17.5 to 23.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Matching Placebo, Part 2: TD-0903 - 3 mg
Comments Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6137
Comments [Not Specified]
Method Van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Common Odds Ratio
Estimated Value 1.142
Confidence Interval (2-Sided) 95%
0.706 to 1.846
Estimation Comments Common Odds Ratio (TD-0903 vs. placebo) and corresponding 95% Wald confidence interval (CI) were obtained from the proportional odds regression model of RFD adjusting for baseline age strata (≤ 60 years vs. > 60 years).
2.Secondary Outcome
Title Part 2: Change From Baseline in SaO2/FiO2 Ratio on Day 7
Hide Description SaO2/FiO2 ratio was calculated as SaO2 divided by FiO2.
Time Frame Baseline and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.
Arm/Group Title Part 2: Matching Placebo Part 2: TD-0903 - 3 mg
Hide Arm/Group Description:
Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.
TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.
Overall Number of Participants Analyzed 86 90
Least Squares Mean (Standard Error)
Unit of Measure: ratio measure
88.97  (7.769) 88.46  (7.654)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Matching Placebo, Part 2: TD-0903 - 3 mg
Comments Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group
Type of Statistical Test Other
Comments Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.
Statistical Test of Hypothesis P-Value 0.962
Comments [Not Specified]
Method Mixed model repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-21.95 to 20.92
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Part 2: Number of Participants in Each Category of the 8-point Ordinal Clinical Status Scale on Days 7, 14, 21, and 28
Hide Description

The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. The scale was as follows:

  • Score 1: Not hospitalized, no limitations on activities
  • Score 2: Not hospitalized, but with limitations on activities and/or requiring home oxygen
  • Score 3: Hospitalized, not requiring supplemental oxygen, and no longer requiring ongoing medical care
  • Score 4: Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19)
  • Score 5: Hospitalized, requiring supplemental oxygen
  • Score 6: Hospitalized, on non-invasive ventilation or high-flow oxygen devices
  • Score 7: Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation
  • Score 8: Death
Time Frame Days 7, 14, 21 and 28
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.
Arm/Group Title Part 2: Matching Placebo Part 2: TD-0903 - 3 mg
Hide Arm/Group Description:
Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.
TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.
Overall Number of Participants Analyzed 102 100
Measure Type: Count of Participants
Unit of Measure: Participants
Day 7 Number Analyzed 102 participants 99 participants
Score 1
6
   5.9%
8
   8.1%
Score 2
12
  11.8%
9
   9.1%
Score 3
1
   1.0%
1
   1.0%
Score 4
25
  24.5%
23
  23.2%
Score 5
42
  41.2%
48
  48.5%
Score 6
7
   6.9%
7
   7.1%
Score 7
7
   6.9%
2
   2.0%
Score 8
2
   2.0%
1
   1.0%
Day 14 Number Analyzed 102 participants 99 participants
Score 1
57
  55.9%
52
  52.5%
Score 2
6
   5.9%
11
  11.1%
Score 3
2
   2.0%
7
   7.1%
Score 4
14
  13.7%
13
  13.1%
Score 5
10
   9.8%
7
   7.1%
Score 6
1
   1.0%
2
   2.0%
Score 7
6
   5.9%
5
   5.1%
Score 8
6
   5.9%
2
   2.0%
Day 21 Number Analyzed 102 participants 99 participants
Score 1
72
  70.6%
72
  72.7%
Score 2
4
   3.9%
9
   9.1%
Score 3
4
   3.9%
6
   6.1%
Score 4
4
   3.9%
0
   0.0%
Score 5
3
   2.9%
4
   4.0%
Score 6
1
   1.0%
0
   0.0%
Score 7
2
   2.0%
3
   3.0%
Score 8
12
  11.8%
5
   5.1%
Day 28 Number Analyzed 102 participants 100 participants
Score 1
79
  77.5%
78
  78.0%
Score 2
5
   4.9%
11
  11.0%
Score 3
0
   0.0%
1
   1.0%
Score 4
1
   1.0%
1
   1.0%
Score 5
3
   2.9%
1
   1.0%
Score 6
0
   0.0%
0
   0.0%
Score 7
1
   1.0%
2
   2.0%
Score 8
13
  12.7%
6
   6.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Matching Placebo, Part 2: TD-0903 - 3 mg
Comments Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group on Day 7
Type of Statistical Test Other
Comments Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.
Statistical Test of Hypothesis P-Value 0.5918
Comments [Not Specified]
Method Van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.153
Confidence Interval (2-Sided) 95%
0.692 to 1.922
Estimation Comments Between-group comparisons analyzed using a proportional odds model adjusting for baseline age strata (≤ 60 years vs. > 60 years).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 2: Matching Placebo, Part 2: TD-0903 - 3 mg
Comments Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group on Day 14
Type of Statistical Test Other
Comments Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.
Statistical Test of Hypothesis P-Value 0.6978
Comments [Not Specified]
Method Van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.105
Confidence Interval (2-Sided) 95%
0.651 to 1.878
Estimation Comments [Not Specified]
Other Statistical Analysis Between-group comparisons analyzed using a proportional odds model adjusting for baseline age strata (≤ 60 years vs. > 60 years).
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 2: Matching Placebo, Part 2: TD-0903 - 3 mg
Comments Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group on Day 21
Type of Statistical Test Other
Comments Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.
Statistical Test of Hypothesis P-Value 0.3990
Comments [Not Specified]
Method Van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.295
Confidence Interval (2-Sided) 95%
0.702 to 2.388
Estimation Comments [Not Specified]
Other Statistical Analysis Between-group comparisons analyzed using a proportional odds model adjusting for baseline age strata (≤ 60 years vs. > 60 years).
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2: Matching Placebo, Part 2: TD-0903 - 3 mg
Comments Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group on Day 28
Type of Statistical Test Other
Comments Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.
Statistical Test of Hypothesis P-Value 0.6445
Comments [Not Specified]
Method Van Elteren test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.180
Confidence Interval (2-Sided) 95%
0.605 to 2.299
Estimation Comments Between-group comparisons analyzed using a proportional odds model adjusting for baseline age strata (≤ 60 years vs. > 60 years).
4.Secondary Outcome
Title Part 2: Number of Participants Alive and Respiratory Failure-free on Day 28
Hide Description Defined as participants who were alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) on Day 28.
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.
Arm/Group Title Part 2: Matching Placebo Part 2: TD-0903 - 3 mg
Hide Arm/Group Description:
Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.
TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.
Overall Number of Participants Analyzed 104 106
Measure Type: Count of Participants
Unit of Measure: Participants
85
  81.7%
92
  86.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Matching Placebo, Part 2: TD-0903 - 3 mg
Comments Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group
Type of Statistical Test Other
Comments Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.
Statistical Test of Hypothesis P-Value 0.3005
Comments The p-value was calculated using the Cochran-Mantel-Haenszel chi-square test stratified by baseline age group (≤ 60 years vs. > 60 years)
Method Cochran-Mantel-Haenszel chi-square test
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 5.06
Confidence Interval (2-Sided) 95%
-4.50 to 14.63
Estimation Comments [Not Specified]
Time Frame Day 1 to Day 28
Adverse Event Reporting Description Safety analysis set - all participants who received at least one dose of study drug.
 
Arm/Group Title Part 1: Matching Placebo Part 1: TD-0903 - 1 mg Part 1: TD-0903 - 3 mg Part 1: TD-0903 - 10 mg Part 2: Matching Placebo Part 2: TD-0903 - 3 mg
Hide Arm/Group Description Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 1 mg. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 10 mg. Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system. TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system. Participants were administered the recommended dose of 3 mg based on the data from Part 1.
All-Cause Mortality
Part 1: Matching Placebo Part 1: TD-0903 - 1 mg Part 1: TD-0903 - 3 mg Part 1: TD-0903 - 10 mg Part 2: Matching Placebo Part 2: TD-0903 - 3 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/6 (33.33%)   1/6 (16.67%)   0/7 (0.00%)   0/6 (0.00%)   13/102 (12.75%)   6/103 (5.83%) 
Hide Serious Adverse Events
Part 1: Matching Placebo Part 1: TD-0903 - 1 mg Part 1: TD-0903 - 3 mg Part 1: TD-0903 - 10 mg Part 2: Matching Placebo Part 2: TD-0903 - 3 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/6 (50.00%)   1/6 (16.67%)   1/7 (14.29%)   0/6 (0.00%)   16/102 (15.69%)   10/103 (9.71%) 
Cardiac disorders             
Cardiac arrest  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  2/102 (1.96%)  0/103 (0.00%) 
Ventricular fibrillation  1  0/6 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
General disorders             
Multiple organ dysfunction syndrome  1  1/6 (16.67%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  1/102 (0.98%)  3/103 (2.91%) 
Sudden death  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/102 (0.98%)  0/103 (0.00%) 
Infections and infestations             
COVID-19  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Bacterial sepsis  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/102 (0.98%)  1/103 (0.97%) 
Septic shock  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/102 (0.98%)  0/103 (0.00%) 
Systemic bacterial infection  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  1/103 (0.97%) 
Investigations             
Alanine aminotransferase increased  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  1/103 (0.97%) 
Aspartate aminotransferase increased  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  1/103 (0.97%) 
Nervous system disorders             
Ischaemic stroke  1  0/6 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/102 (0.00%)  1/103 (0.97%) 
Syncope  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/102 (0.98%)  0/103 (0.00%) 
Renal and urinary disorders             
Acute kidney injury  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  3/102 (2.94%)  0/103 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Acute respiratory distress syndrome  1  2/6 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  3/103 (2.91%) 
Acute respiratory failure  1  0/6 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  3/102 (2.94%)  0/103 (0.00%) 
Pulmonary embolism  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  4/102 (3.92%)  0/103 (0.00%) 
Respiratory failure  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  5/102 (4.90%)  3/103 (2.91%) 
Pneumothorax  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/102 (0.98%)  1/103 (0.97%) 
Vascular disorders             
Shock  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  2/102 (1.96%)  1/103 (0.97%) 
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Matching Placebo Part 1: TD-0903 - 1 mg Part 1: TD-0903 - 3 mg Part 1: TD-0903 - 10 mg Part 2: Matching Placebo Part 2: TD-0903 - 3 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   4/6 (66.67%)   1/7 (14.29%)   5/6 (83.33%)   18/102 (17.65%)   15/103 (14.56%) 
Blood and lymphatic system disorders             
Lymphopenia  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Cardiac disorders             
Bradycardia  1  0/6 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Sinus tachycardia  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  1/103 (0.97%) 
Gastrointestinal disorders             
Abdominal pain  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Diarrhoea  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  7/102 (6.86%)  3/103 (2.91%) 
Nausea  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/102 (0.98%)  0/103 (0.00%) 
Vomiting  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
General disorders             
Pyrexia  1  1/6 (16.67%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Hepatobiliary disorders             
Hepatic failure  1  0/6 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  2/102 (1.96%)  1/103 (0.97%) 
Hypertransaminasaemia  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/102 (0.00%)  0/103 (0.00%) 
Infections and infestations             
Oropharyngeal candidiasis  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/102 (0.00%)  0/103 (0.00%) 
Vascular device infection  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Investigations             
Alanine aminotransferase increased  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  6/102 (5.88%)  5/103 (4.85%) 
Metabolism and nutrition disorders             
Hyperglycaemia  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  2/102 (1.96%)  3/103 (2.91%) 
Hypokalaemia  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Nervous system disorders             
Dysgeusia  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  1/102 (0.98%)  1/103 (0.97%) 
Headache  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  1/103 (0.97%) 
Tremor  1  0/6 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Psychiatric disorders             
Depressed mood  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Depression  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Insomnia  1  0/6 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  1/103 (0.97%) 
Renal and urinary disorders             
Chronic kidney disease  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Cough  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  3/6 (50.00%)  1/102 (0.98%)  3/103 (2.91%) 
Oropharyngeal pain  1  0/6 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  1/6 (16.67%)  1/102 (0.98%)  0/103 (0.00%) 
Pulmonary hypertension  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Upper-airway cough syndrome  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/102 (0.00%)  0/103 (0.00%) 
Skin and subcutaneous tissue disorders             
Pruritus  1  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  0/103 (0.00%) 
Vascular disorders             
Hypertension  1  0/6 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/102 (0.00%)  4/103 (3.88%) 
Hypotension  1  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  1/102 (0.98%)  1/103 (0.97%) 
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Monitor
Organization: Theravance Biopharma
Phone: 1-855-633-8479
EMail: medinfo@theravance.com
Layout table for additonal information
Responsible Party: Theravance Biopharma
ClinicalTrials.gov Identifier: NCT04402866    
Other Study ID Numbers: 0188
2020-001807-18 ( EudraCT Number )
First Submitted: May 22, 2020
First Posted: May 27, 2020
Results First Submitted: February 25, 2022
Results First Posted: March 17, 2022
Last Update Posted: March 17, 2022