Trial Outcomes & Findings for A Dose Escalation Study of BLU-5937 in Unexplained or Refractory Chronic Cough (NCT NCT03979638)
NCT ID: NCT03979638
Last Updated: 2021-08-03
Results Overview
Change in awake cough frequency (average hourly cough frequency while the subject is awake ) evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
68 participants
Primary outcome timeframe
Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses
Results posted on
2021-08-03
Participant Flow
Participants were recruited at 16 clinical trial sites in the United-Kingdom and in United States.
A total of 68 participants were randomized to receive the study drug (BLU-5937) followed by placebo (33 participants) or placebo followed by the study drug (35 participants).
Participant milestones
| Measure |
BLU-5937 > Placebo
Randomized crossover design of 4 different doses (25, 50, 100, 200 mg BID) of BLU-5937 tablets to be administered orally BID
BLU-5937: Four escalating doses of BLU-5937 administered BID over the course of the study followed by matching Placebo
|
Placebo > BLU-5937
Randomized crossover design of matching placebo tablets to be administered orally BID
Placebo: Matching placebo for BLU-5937 follow by four escalating doses of BLU-5937
|
|---|---|---|
|
Period 1
STARTED
|
33
|
35
|
|
Period 1
COMPLETED
|
26
|
28
|
|
Period 1
NOT COMPLETED
|
7
|
7
|
|
Period 2
STARTED
|
26
|
28
|
|
Period 2
COMPLETED
|
25
|
27
|
|
Period 2
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
BLU-5937 > Placebo
Randomized crossover design of 4 different doses (25, 50, 100, 200 mg BID) of BLU-5937 tablets to be administered orally BID
BLU-5937: Four escalating doses of BLU-5937 administered BID over the course of the study followed by matching Placebo
|
Placebo > BLU-5937
Randomized crossover design of matching placebo tablets to be administered orally BID
Placebo: Matching placebo for BLU-5937 follow by four escalating doses of BLU-5937
|
|---|---|---|
|
Period 1
Physician Decision
|
1
|
1
|
|
Period 1
Withdrawal by Subject
|
4
|
3
|
|
Period 1
Study terminated by Sponsor
|
1
|
3
|
|
Period 1
Protocol Violation
|
1
|
0
|
|
Period 2
Study terminated by Sponsor
|
1
|
1
|
Baseline Characteristics
A Dose Escalation Study of BLU-5937 in Unexplained or Refractory Chronic Cough
Baseline characteristics by cohort
| Measure |
BLU-5937 > Placebo
n=33 Participants
Randomized crossover design of 4 different doses (25, 50, 100, 200 mg BID) of BLU-5937 tablets to be administered orally BID
BLU-5937: Four escalating doses of BLU-5937 administered BID over the course of the study followed by matching Placebo
|
Placebo > BLU-5937
n=35 Participants
Randomized crossover design of matching placebo tablets to be administered orally BID
Placebo: Matching placebo for BLU-5937 followed by four escalating doses of BLU-5937
|
Total
n=68 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.3 years
STANDARD_DEVIATION 11.49 • n=5 Participants
|
63.7 years
STANDARD_DEVIATION 9.70 • n=7 Participants
|
64.0 years
STANDARD_DEVIATION 10.53 • n=5 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
58 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
33 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 dosesPopulation: Analysis population consisted of all randomized subjects who took at least one dose of study drug and provided at least one baseline and at least one post-baseline cough frequency measurement
Change in awake cough frequency (average hourly cough frequency while the subject is awake ) evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected
Outcome measures
| Measure |
BLU-5937 - 25 mg
n=60 Participants
BLU-5937 25 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 25 mg
n=59 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
BLU-5937 - 50 mg
n=59 Participants
BLU-5937 50 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 50 mg
n=58 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
BLU-5937 - 100 mg
n=56 Participants
BLU-5937 100 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 100 mg
n=58 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
BLU-5937 - 200 mg
n=58 Participants
BLU-5937 200 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 200 mg
n=58 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
|---|---|---|---|---|---|---|---|---|
|
Change in Awake Objective Cough Frequency on Log-transformed Scale
|
-0.19 Log coughs/hour
Interval -0.29 to -0.08
|
-0.07 Log coughs/hour
Interval -0.19 to 0.05
|
-0.20 Log coughs/hour
Interval -0.32 to -0.08
|
-0.14 Log coughs/hour
Interval -0.26 to -0.01
|
-0.25 Log coughs/hour
Interval -0.4 to -0.09
|
-0.17 Log coughs/hour
Interval -0.3 to -0.04
|
-0.33 Log coughs/hour
Interval -0.49 to -0.17
|
-0.14 Log coughs/hour
Interval -0.29 to 0.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 dosesChange in awake cough frequency (average hourly cough frequency while the subject is awake) in the a pre-specified subgroup of participants with awake cough frequency \> or = 20 coughs/hour at baseline evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected
Outcome measures
| Measure |
BLU-5937 - 25 mg
n=46 Participants
BLU-5937 25 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 25 mg
n=46 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
BLU-5937 - 50 mg
n=45 Participants
BLU-5937 50 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 50 mg
n=46 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
BLU-5937 - 100 mg
n=44 Participants
BLU-5937 100 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 100 mg
n=47 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
BLU-5937 - 200 mg
n=45 Participants
BLU-5937 200 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 200 mg
n=46 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
|---|---|---|---|---|---|---|---|---|
|
Change in Awake Cough Frequency on Log-transformed Scale in the Subgroup of Participants With Awake Cough Frequency > or = 20 Coughs/Hour at Baseline
|
-0.23 Log coughs/hour
Interval -0.34 to -0.11
|
0.00 Log coughs/hour
Interval -0.09 to 0.1
|
-0.29 Log coughs/hour
Interval -0.42 to -0.15
|
-0.09 Log coughs/hour
Interval -0.21 to 0.03
|
-0.33 Log coughs/hour
Interval -0.51 to -0.16
|
-0.12 Log coughs/hour
Interval -0.25 to 0.01
|
-0.41 Log coughs/hour
Interval -0.58 to -0.24
|
-0.09 Log coughs/hour
Interval -0.23 to 0.05
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12,16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 dosesChange in awake cough frequency (average hourly cough frequency while the subject is awake) in the a pre-specified subgroup of participants with awake cough frequency \> or = median (32.4 coughs/hour) at baseline evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected
Outcome measures
| Measure |
BLU-5937 - 25 mg
n=28 Participants
BLU-5937 25 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 25 mg
n=30 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
BLU-5937 - 50 mg
n=28 Participants
BLU-5937 50 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 50 mg
n=31 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
BLU-5937 - 100 mg
n=27 Participants
BLU-5937 100 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 100 mg
n=31 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
BLU-5937 - 200 mg
n=28 Participants
BLU-5937 200 mg tablet administered orally BID for 4 days
|
Placebo Comparator - 200 mg
n=31 Participants
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
|---|---|---|---|---|---|---|---|---|
|
Change in Awake Cough Frequency on Log-transformed Scale in the Subgroup of Participants With Awake Cough Frequency > or = Median (32.4 Coughs/Hour) at Baseline
|
-0.31 Log coughs/hour
Interval -0.45 to -0.18
|
0.02 Log coughs/hour
Interval -0.11 to 0.15
|
-0.42 Log coughs/hour
Interval -0.55 to -0.28
|
-0.08 Log coughs/hour
Interval -0.22 to 0.05
|
-0.44 Log coughs/hour
Interval -0.6 to -0.27
|
-0.09 Log coughs/hour
Interval -0.24 to 0.06
|
-0.49 Log coughs/hour
Interval -0.68 to -0.31
|
-0.10 Log coughs/hour
Interval -0.24 to 0.03
|
Adverse Events
BLU-5937 - 25 mg
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
BLU-5937 - 50 mg
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
BLU-5937 - 100 mg
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
BLU-5937 - 200 mg
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
BLU-5937 - 25 mg
n=61 participants at risk
BLU-5937 25 mg tablet administered orally BID for 4 days
|
BLU-5937 - 50 mg
n=61 participants at risk
BLU-5937 50 mg tablet administered orally BID for 4 days
|
BLU-5937 - 100 mg
n=60 participants at risk
BLU-5937 100 mg tablet administered orally BID for 4 days
|
BLU-5937 - 200 mg
n=58 participants at risk
BLU-5937 200 mg tablet administered orally BID for 4 days
|
Placebo
n=61 participants at risk
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
|---|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
colorectal cancer
|
0.00%
0/61 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
0.00%
0/61 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
0.00%
0/60 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
0.00%
0/58 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
1.6%
1/61 • Number of events 1 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
Other adverse events
| Measure |
BLU-5937 - 25 mg
n=61 participants at risk
BLU-5937 25 mg tablet administered orally BID for 4 days
|
BLU-5937 - 50 mg
n=61 participants at risk
BLU-5937 50 mg tablet administered orally BID for 4 days
|
BLU-5937 - 100 mg
n=60 participants at risk
BLU-5937 100 mg tablet administered orally BID for 4 days
|
BLU-5937 - 200 mg
n=58 participants at risk
BLU-5937 200 mg tablet administered orally BID for 4 days
|
Placebo
n=61 participants at risk
Matching Placebo for BLU-5937 administered orally BID for 4 days
|
|---|---|---|---|---|---|
|
Nervous system disorders
Headache
|
4.9%
3/61 • Number of events 3 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
3.3%
2/61 • Number of events 2 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
6.7%
4/60 • Number of events 4 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
5.2%
3/58 • Number of events 3 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
11.5%
7/61 • Number of events 7 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
|
Nervous system disorders
Dysgeusia
|
4.9%
3/61 • Number of events 3 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
8.2%
5/61 • Number of events 5 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
8.3%
5/60 • Number of events 5 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
6.9%
4/58 • Number of events 4 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
3.3%
2/61 • Number of events 2 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
|
Nervous system disorders
Dizziness
|
4.9%
3/61 • Number of events 3 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
6.6%
4/61 • Number of events 4 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
5.0%
3/60 • Number of events 3 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
3.4%
2/58 • Number of events 2 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
3.3%
2/61 • Number of events 2 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
|
Gastrointestinal disorders
Diarrhoea
|
1.6%
1/61 • Number of events 1 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
1.6%
1/61 • Number of events 1 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
1.7%
1/60 • Number of events 1 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
0.00%
0/58 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
4.9%
3/61 • Number of events 3 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
|
Infections and infestations
Upper respiratory tract infection
|
3.3%
2/61 • Number of events 2 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
6.6%
4/61 • Number of events 4 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
6.7%
4/60 • Number of events 4 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
5.2%
3/58 • Number of events 3 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
4.9%
3/61 • Number of events 3 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.3%
2/61 • Number of events 2 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
4.9%
3/61 • Number of events 3 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
3.3%
2/60 • Number of events 2 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
1.7%
1/58 • Number of events 1 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
9.8%
6/61 • Number of events 6 • All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee No data collected as part of this study will be utilized in any written work, including publications, without the written consent of sponsor.
- Publication restrictions are in place
Restriction type: OTHER