Trial Outcomes & Findings for Efficacy and Safety of BCX7353 to Prevent Angioedema Attacks in Subjects With Hereditary Angioedema (NCT NCT02870972)
NCT ID: NCT02870972
Last Updated: 2021-03-23
Results Overview
Efficacy was evaluated by the number of acute angioedema attacks. To ensure that consistent, objective assessments were used in accepting subject-reported attack data, a panel of expert physicians in the treatment of HAE patients adjudicated all subject-reported attacks prior to their inclusion in primary efficacy analyses.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
75 participants
Primary outcome timeframe
Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).
Results posted on
2021-03-23
Participant Flow
HAE subjects attended a Screening Visit up to 21 days before the baseline visit, for assessment of eligibility to participate in the study.
Participant milestones
| Measure |
Part 1: Berotralstat 350 mg
Berotralstat capsules, 350 mg dose administered once per day for 28 days
|
Parts 2 & 3: Berotralstat 250 mg
Berotralstat capsules, 250 mg dose administered once per day for 28 days
|
Parts 2 & 3: Berotralstat 125 mg
Berotralstat capsules, 125 mg dose administered once per day for 28 days
|
Part 3: Berotralstat 62.5 mg
Berotralstat capsules, 62.5 mg dose administered once per day for 28 days
|
Parts 1, 2 & 3: Placebo
Placebo capsules, administered once per day for 28 days
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
18
|
14
|
14
|
7
|
22
|
|
Overall Study
COMPLETED
|
17
|
14
|
14
|
7
|
22
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Part 1: Berotralstat 350 mg
Berotralstat capsules, 350 mg dose administered once per day for 28 days
|
Parts 2 & 3: Berotralstat 250 mg
Berotralstat capsules, 250 mg dose administered once per day for 28 days
|
Parts 2 & 3: Berotralstat 125 mg
Berotralstat capsules, 125 mg dose administered once per day for 28 days
|
Part 3: Berotralstat 62.5 mg
Berotralstat capsules, 62.5 mg dose administered once per day for 28 days
|
Parts 1, 2 & 3: Placebo
Placebo capsules, administered once per day for 28 days
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Efficacy and Safety of BCX7353 to Prevent Angioedema Attacks in Subjects With Hereditary Angioedema
Baseline characteristics by cohort
| Measure |
Part 1: Berotralstat 350 mg
n=18 Participants
Berotralstat capsules, 350 mg dose administered once per day for 28 days
|
Parts 2 & 3: Berotralstat 250 mg
n=14 Participants
Berotralstat capsules, 250 mg dose administered once per day for 28 days
|
Parts 2 & 3: Berotralstat 125 mg
n=14 Participants
Berotralstat capsules, 125 mg dose administered once per day for 28 days
|
Part 3: Berotralstat 62.5 mg
n=7 Participants
Berotralstat capsules, 62.5 mg dose administered once per day for 28 days
|
Parts 1, 2 & 3: Placebo
n=22 Participants
Placebo capsules, administered once per day for 28 days
|
Total
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
43.8 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
40.9 years
STANDARD_DEVIATION 13.4 • n=7 Participants
|
48.1 years
STANDARD_DEVIATION 12.6 • n=5 Participants
|
38.9 years
STANDARD_DEVIATION 16.6 • n=4 Participants
|
46.8 years
STANDARD_DEVIATION 11.1 • n=21 Participants
|
44.5 years
STANDARD_DEVIATION 12.5 • n=8 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
46 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
29 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
68 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
|
Region of Enrollment
Austria
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
1 participants
n=21 Participants
|
6 participants
n=8 Participants
|
|
Region of Enrollment
Hungary
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
2 participants
n=21 Participants
|
3 participants
n=8 Participants
|
|
Region of Enrollment
North Macedonia
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
5 participants
n=5 Participants
|
0 participants
n=4 Participants
|
2 participants
n=21 Participants
|
9 participants
n=8 Participants
|
|
Region of Enrollment
Denmark
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
1 participants
n=4 Participants
|
3 participants
n=21 Participants
|
8 participants
n=8 Participants
|
|
Region of Enrollment
United Kingdom
|
6 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
11 participants
n=8 Participants
|
|
Region of Enrollment
Italy
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
2 participants
n=21 Participants
|
7 participants
n=8 Participants
|
|
Region of Enrollment
Australia
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
3 participants
n=8 Participants
|
|
Region of Enrollment
Switzerland
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
2 participants
n=21 Participants
|
5 participants
n=8 Participants
|
|
Region of Enrollment
Germany
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
0 participants
n=4 Participants
|
5 participants
n=21 Participants
|
12 participants
n=8 Participants
|
|
Region of Enrollment
Spain
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
3 participants
n=21 Participants
|
6 participants
n=8 Participants
|
|
Region of Enrollment
France
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
1 participants
n=21 Participants
|
5 participants
n=8 Participants
|
|
Adjusted qualifying HAE attack rate
|
0.84 HAE attacks/week
STANDARD_DEVIATION 0.35 • n=5 Participants
|
0.91 HAE attacks/week
STANDARD_DEVIATION 0.43 • n=7 Participants
|
0.94 HAE attacks/week
STANDARD_DEVIATION 0.40 • n=5 Participants
|
1.05 HAE attacks/week
STANDARD_DEVIATION 0.44 • n=4 Participants
|
0.87 HAE attacks/week
STANDARD_DEVIATION 0.45 • n=21 Participants
|
0.90 HAE attacks/week
STANDARD_DEVIATION 0.41 • n=8 Participants
|
PRIMARY outcome
Timeframe: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).Population: The Full Analysis Set population included all subjects who were randomized, received at least 1 dose of study drug, and had post baseline HAE diary data recorded.
Efficacy was evaluated by the number of acute angioedema attacks. To ensure that consistent, objective assessments were used in accepting subject-reported attack data, a panel of expert physicians in the treatment of HAE patients adjudicated all subject-reported attacks prior to their inclusion in primary efficacy analyses.
Outcome measures
| Measure |
Berotralstat 350 mg
n=18 Participants
Berotralstat capsules (350 mg) administered QD for 28 days
|
Berotralstat 250 mg
n=14 Participants
Berotralstat capsules (250 mg) administered QD for 28 days
|
Berotralstat 125 mg
n=14 Participants
Berotralstat capsules (125 mg) administered QD for 28 days
|
Berotralstat 62.5 mg
n=7 Participants
Berotralstat capsules (62.5 mg) administered QD for 28 days
|
Berotralstat
n=53 Participants
Berotralstat capsules administered QD for 28 days
|
Placebo
n=22 Participants
Placebo capsules administered QD for 28 days
|
|---|---|---|---|---|---|---|
|
Number of Confirmed HAE Attacks
|
0.519 HAE attacks per week
Standard Error 0.115
|
0.527 HAE attacks per week
Standard Error 0.130
|
0.249 HAE attacks per week
Standard Error 0.130
|
0.852 HAE attacks per week
Standard Error 0.185
|
0.494 HAE attacks per week
Standard Error 0.067
|
0.952 HAE attacks per week
Standard Error 0.104
|
PRIMARY outcome
Timeframe: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).Population: The Full Analysis Set population included all subjects who were randomized, received at least 1 dose of study drug, and had post-baseline HAE diary data recorded.
Assessment of the proportion of subjects who had no HAE attacks during the entire dosing period
Outcome measures
| Measure |
Berotralstat 350 mg
n=18 Participants
Berotralstat capsules (350 mg) administered QD for 28 days
|
Berotralstat 250 mg
n=14 Participants
Berotralstat capsules (250 mg) administered QD for 28 days
|
Berotralstat 125 mg
n=14 Participants
Berotralstat capsules (125 mg) administered QD for 28 days
|
Berotralstat 62.5 mg
n=7 Participants
Berotralstat capsules (62.5 mg) administered QD for 28 days
|
Berotralstat
n=53 Participants
Berotralstat capsules administered QD for 28 days
|
Placebo
n=22 Participants
Placebo capsules administered QD for 28 days
|
|---|---|---|---|---|---|---|
|
Proportion of Subjects Who Were HAE Attack-free During the Entire Dosing Period
HAE Attack Free
|
4 participants
|
3 participants
|
4 participants
|
0 participants
|
11 participants
|
1 participants
|
|
Proportion of Subjects Who Were HAE Attack-free During the Entire Dosing Period
HAE Attack Free (missing diary = attack)
|
2 participants
|
3 participants
|
4 participants
|
0 participants
|
9 participants
|
1 participants
|
|
Proportion of Subjects Who Were HAE Attack-free During the Entire Dosing Period
HAE Attack Free (missing diary = exclude)
|
2 participants
|
3 participants
|
4 participants
|
0 participants
|
9 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).Population: The Full Analysis Set population included all subjects who were randomized, received at least 1 dose of study drug, and had post baseline HAE diary data recorded.
A prespecified secondary endpoint analyzed confirmed attacks by anatomical location; abdominal HAE attacks included any abdominal symptoms (i.e. swelling in the stomach/gut, or any symptoms of nausea, vomiting, or abdominal pain)
Outcome measures
| Measure |
Berotralstat 350 mg
n=18 Participants
Berotralstat capsules (350 mg) administered QD for 28 days
|
Berotralstat 250 mg
n=14 Participants
Berotralstat capsules (250 mg) administered QD for 28 days
|
Berotralstat 125 mg
n=14 Participants
Berotralstat capsules (125 mg) administered QD for 28 days
|
Berotralstat 62.5 mg
n=7 Participants
Berotralstat capsules (62.5 mg) administered QD for 28 days
|
Berotralstat
n=53 Participants
Berotralstat capsules administered QD for 28 days
|
Placebo
n=22 Participants
Placebo capsules administered QD for 28 days
|
|---|---|---|---|---|---|---|
|
Number of Confirmed Abdominal HAE Attacks
|
0.366 HAE attacks per week
Standard Error 0.073
|
0.324 HAE attacks per week
Standard Error 0.082
|
0.173 HAE attacks per week
Standard Error 0.083
|
0.404 HAE attacks per week
Standard Error 0.117
|
0.309 HAE attacks per week
Standard Error 0.042
|
0.370 HAE attacks per week
Standard Error 0.066
|
SECONDARY outcome
Timeframe: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).Population: The Full Analysis Set population included all subjects who were randomized, received at least 1 dose of study drug, and had post baseline HAE diary data recorded.
A prespecified secondary endpoint analyzed confirmed attacks by anatomical location; peripheral attacks included any with peripheral symptoms only (i.e. peripheral swelling or erythema marginatum).
Outcome measures
| Measure |
Berotralstat 350 mg
n=18 Participants
Berotralstat capsules (350 mg) administered QD for 28 days
|
Berotralstat 250 mg
n=14 Participants
Berotralstat capsules (250 mg) administered QD for 28 days
|
Berotralstat 125 mg
n=14 Participants
Berotralstat capsules (125 mg) administered QD for 28 days
|
Berotralstat 62.5 mg
n=7 Participants
Berotralstat capsules (62.5 mg) administered QD for 28 days
|
Berotralstat
n=53 Participants
Berotralstat capsules administered QD for 28 days
|
Placebo
n=22 Participants
Placebo capsules administered QD for 28 days
|
|---|---|---|---|---|---|---|
|
Number of Confirmed Peripheral HAE Attacks
|
0.160 HAE attacks per week
Standard Error 0.086
|
0.143 HAE attacks per week
Standard Error 0.097
|
0.098 HAE attacks per week
Standard Error 0.097
|
0.463 HAE attacks per week
Standard Error 0.138
|
0.179 HAE attacks per week
Standard Error 0.050
|
0.543 HAE attacks per week
Standard Error 0.078
|
SECONDARY outcome
Timeframe: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).Population: The Full Analysis Set population included all subjects who were randomized, received at least 1 dose of study drug, and had post baseline HAE diary data recorded.
A prespecified secondary endpoint analyzed the number of attacks requiring treatment with acute HAE medication (Berinert, Firazyr, Cinryze or Ruconest)
Outcome measures
| Measure |
Berotralstat 350 mg
n=18 Participants
Berotralstat capsules (350 mg) administered QD for 28 days
|
Berotralstat 250 mg
n=14 Participants
Berotralstat capsules (250 mg) administered QD for 28 days
|
Berotralstat 125 mg
n=14 Participants
Berotralstat capsules (125 mg) administered QD for 28 days
|
Berotralstat 62.5 mg
n=7 Participants
Berotralstat capsules (62.5 mg) administered QD for 28 days
|
Berotralstat
n=53 Participants
Berotralstat capsules administered QD for 28 days
|
Placebo
n=22 Participants
Placebo capsules administered QD for 28 days
|
|---|---|---|---|---|---|---|
|
HAE Attacks Requiring Treatment
|
0.483 HAE attacks per week
Standard Error 0.109
|
0.449 HAE attacks per week
Standard Error 0.123
|
0.218 HAE attacks per week
Standard Error 0.1231
|
0.833 HAE attacks per week
Standard Error 0.174
|
0.450 HAE attacks per week
Standard Error 0.063
|
0.776 HAE attacks per week
Standard Error 0.098
|
SECONDARY outcome
Timeframe: 28-day treatment period + 1 dayPopulation: The Full Analysis Set population included all subjects who were randomized, received at least 1 dose of study drug, and had post baseline HAE diary data recorded.
Activity of disease (i.e. disease severity) was assessed using a modified Angioedema Activity Score (AAS). The relevant endpoint for this study was the total modified AAS score, defined as the sum of the individual scores for 4 AAS domains (daily activities, appearance, physical discomfort, and overall severity) for all subject-reported attacks reported during the treatment period. Individual domain scores were based on answers to questions each of which had 4 possible responses scored 0-3 (0 - no impact; 1-3 - increasing levels of impact). The total modified AAS score per attack could range from 0 to 12; lower scores \& higher scores represent lower \& higher disease activities, respectively. However, the overall total modified AAS score reported for this study included the total scores for all subject-reported attacks, therefore the upper limit of the range was subject-specific. The statistical analysis of the total modified AAS scores for the treatment period is presented below.
Outcome measures
| Measure |
Berotralstat 350 mg
n=18 Participants
Berotralstat capsules (350 mg) administered QD for 28 days
|
Berotralstat 250 mg
n=14 Participants
Berotralstat capsules (250 mg) administered QD for 28 days
|
Berotralstat 125 mg
n=14 Participants
Berotralstat capsules (125 mg) administered QD for 28 days
|
Berotralstat 62.5 mg
n=7 Participants
Berotralstat capsules (62.5 mg) administered QD for 28 days
|
Berotralstat
n=22 Participants
Berotralstat capsules administered QD for 28 days
|
Placebo
Placebo capsules administered QD for 28 days
|
|---|---|---|---|---|---|---|
|
HAE Disease Activity - Modified Angioedema Activity Score
|
14.070 score on a scale
Standard Error 2.610
|
9.416 score on a scale
Standard Error 2.952
|
7.256 score on a scale
Standard Error 2.954
|
22.559 score on a scale
Standard Error 4.200
|
18.519 score on a scale
Standard Error 2.356
|
—
|
SECONDARY outcome
Timeframe: The subject-completed AE-QoL was administered at baseline (Day 1) and at Day 29Population: The Full Analysis Set population included all subjects who were randomized, received at least 1 dose of study drug, and had post baseline HAE diary data recorded.
Quality of Life (QoL) specific to hereditary angioedema (HAE) was assessed at baseline and Day 29 by a questionnaire (i.e. AE-QoL) consisting of 17 questions that spanned 4 domains (functioning, fatigue/mood, fear/shame, and nutrition). Each AE-QoL question had 5 answer options (scored 1-5), with lower and higher scores indicting less and more adverse impact, respectively. Per-subject scores for each domain were computed using the appropriate scoring algorithm applied to the question response scores for each domain. Per-subject total scores (including all 4 domains) were similarly computed using the question response scores for all 17 questions. The outputs from the scoring algorithm were normalized on a scale ranging from 0 (less adverse impact) to 100 (most adverse impact). The statistical analysis of the AE-QoL total score change from baseline to Day 29 is presented below.
Outcome measures
| Measure |
Berotralstat 350 mg
n=17 Participants
Berotralstat capsules (350 mg) administered QD for 28 days
|
Berotralstat 250 mg
n=14 Participants
Berotralstat capsules (250 mg) administered QD for 28 days
|
Berotralstat 125 mg
n=14 Participants
Berotralstat capsules (125 mg) administered QD for 28 days
|
Berotralstat 62.5 mg
n=7 Participants
Berotralstat capsules (62.5 mg) administered QD for 28 days
|
Berotralstat
n=22 Participants
Berotralstat capsules administered QD for 28 days
|
Placebo
Placebo capsules administered QD for 28 days
|
|---|---|---|---|---|---|---|
|
Angioedema Quality of Life (AE-QoL)
|
-12.59 AE-QoL score - change from baseline
Standard Error 4.04
|
-13.39 AE-QoL score - change from baseline
Standard Error 4.44
|
-28.95 AE-QoL score - change from baseline
Standard Error 4.44
|
-12.30 AE-QoL score - change from baseline
Standard Error 6.32
|
-4.47 AE-QoL score - change from baseline
Standard Error 3.54
|
—
|
SECONDARY outcome
Timeframe: The DASS was administered at baseline (Day 1), Day 14, and Day 29.Population: The Full Analysis Set population included all subjects who were randomized, received at least 1 dose of study drug, and had post baseline HAE diary data recorded. Only data from subjects who completed the DASS-42 questionnaire (i.e. 3 DASS scales each containing 14 items) were included in this analyses. Data collected on the DASS-21 questionnaire were excluded.
The Depression, Anxiety \& Stress Scale (DASS) was used to measure the negative emotional states of depression, anxiety \& stress. This assessment was based on a DASS questionnaire administered at baseline, Day 14 \& Day 29. The questionnaire consisted of 3 DASS scales (depression, anxiety \& stress) containing 14 items each on a scale of 0 to 3 (0, did not apply to me at all; 1, applied to me to some degree/some of the time; 2, applied to me to a considerable degree/a good part of the time; 3, applied to me very much or most of the time). Per-subject scores for the depression, anxiety \& stress scales were obtained by summing the scores for the appropriate questionnaire items for the respective category. Total DASS scores were then derived as the sum of the 3 individual scales \& ranged from 0 to 126. Higher \& lower total scores are associated with more \& less adverse impact, respectively. The statistical analysis of the total DASS score change from baseline to Day 29 is presented below.
Outcome measures
| Measure |
Berotralstat 350 mg
n=16 Participants
Berotralstat capsules (350 mg) administered QD for 28 days
|
Berotralstat 250 mg
n=13 Participants
Berotralstat capsules (250 mg) administered QD for 28 days
|
Berotralstat 125 mg
n=14 Participants
Berotralstat capsules (125 mg) administered QD for 28 days
|
Berotralstat 62.5 mg
n=6 Participants
Berotralstat capsules (62.5 mg) administered QD for 28 days
|
Berotralstat
n=19 Participants
Berotralstat capsules administered QD for 28 days
|
Placebo
Placebo capsules administered QD for 28 days
|
|---|---|---|---|---|---|---|
|
DASS (Depression, Anxiety and Stress Scales)
|
-7.627 DASS score - D29 change from baseline
Standard Error 3.275
|
-6.429 DASS score - D29 change from baseline
Standard Error 3.609
|
-10.840 DASS score - D29 change from baseline
Standard Error 3.477
|
-9.141 DASS score - D29 change from baseline
Standard Error 5.336
|
0.643 DASS score - D29 change from baseline
Standard Error 2.984
|
—
|
Adverse Events
Berotralstat 350 mg
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
Berotralstat 250 mg
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Berotralstat 125 mg
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Berotralstat 62.5 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Berotralstat 350 mg
n=18 participants at risk
Berotralstat capsules (350 mg) administered QD for 28 days
|
Berotralstat 250 mg
n=14 participants at risk
Berotralstat capsules (250 mg) administered QD for 28 days
|
Berotralstat 125 mg
n=14 participants at risk
Berotralstat capsules (125 mg) administered QD for 28 days
|
Berotralstat 62.5 mg
n=7 participants at risk
Berotralstat capsules (62.5 mg) administered QD for 28 days
|
Placebo
n=22 participants at risk
Placebo capsules administered QD for 28 days
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal infection
|
0.00%
0/18 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/22 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
Other adverse events
| Measure |
Berotralstat 350 mg
n=18 participants at risk
Berotralstat capsules (350 mg) administered QD for 28 days
|
Berotralstat 250 mg
n=14 participants at risk
Berotralstat capsules (250 mg) administered QD for 28 days
|
Berotralstat 125 mg
n=14 participants at risk
Berotralstat capsules (125 mg) administered QD for 28 days
|
Berotralstat 62.5 mg
n=7 participants at risk
Berotralstat capsules (62.5 mg) administered QD for 28 days
|
Placebo
n=22 participants at risk
Placebo capsules administered QD for 28 days
|
|---|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/18 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
4.5%
1/22 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Investigations
Alanine aminotransferase increased
|
11.1%
2/18 • Number of events 2 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/22 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Nervous system disorders
Headache
|
5.6%
1/18 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
14.3%
2/14 • Number of events 2 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
28.6%
2/7 • Number of events 2 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
18.2%
4/22 • Number of events 4 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Nervous system disorders
Migraine
|
5.6%
1/18 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/22 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
General disorders
Fatigue
|
11.1%
2/18 • Number of events 2 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
14.3%
1/7 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
4.5%
1/22 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
General disorders
Influenza like illness
|
0.00%
0/18 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
4.5%
1/22 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
3/18 • Number of events 3 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
14.3%
2/14 • Number of events 2 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/22 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.6%
1/18 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
14.3%
1/7 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/22 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Gastrointestinal disorders
Diarrhoea
|
22.2%
4/18 • Number of events 4 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
14.3%
2/14 • Number of events 2 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
9.1%
2/22 • Number of events 2 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Gastrointestinal disorders
Flatulence
|
11.1%
2/18 • Number of events 2 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/22 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Gastrointestinal disorders
Nausea
|
16.7%
3/18 • Number of events 3 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
21.4%
3/14 • Number of events 3 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/22 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Gastrointestinal disorders
Vomiting
|
11.1%
2/18 • Number of events 2 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/22 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Gastrointestinal disorders
Constipation
|
5.6%
1/18 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
4.5%
1/22 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/18 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
4.5%
1/22 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/18 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
9.1%
2/22 • Number of events 2 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.6%
1/18 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
4.5%
1/22 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Infections and infestations
Nasopharyngitis
|
27.8%
5/18 • Number of events 5 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
28.6%
2/7 • Number of events 2 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
27.3%
6/22 • Number of events 6 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Infections and infestations
Pharyngitis
|
5.6%
1/18 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/22 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Infections and infestations
Gastrointestinal infection
|
5.6%
1/18 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/22 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/18 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
7.1%
1/14 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/14 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
0.00%
0/7 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
4.5%
1/22 • Number of events 1 • Adverse event data were collected from Day 1 of the study treatment period until 30 days after the last dose of study drug. Last dose was on study day 28 except in the event of early termination.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place