Trial Outcomes & Findings for Efficacy and Safety Study of BCX7353 as an Oral Treatment for the Prevention of Attacks in HAE (NCT NCT03485911)

Last Updated: 2023-06-26

Results Overview

Treatment comparisons between each berotralstat dose and placebo in the rate of investigator-confirmed HAE attacks during the Part 1 dosing period were analyzed using a negative binomial model. The number of investigator-confirmed attacks was included as the dependent variable, the treatment was included as a fixed effect, the stratification variable (baseline attack rate) was included as a covariate, and the logarithm of duration on treatment was included as an offset variable. The estimated attack rate for each treatment group, the treatment differences expressed as the attack rate ratio (berotralstat over placebo rate ratio), and the associated 95% confidence intervals (CIs) were provided from the negative binomial model.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

121 participants

Primary outcome timeframe

24 weeks

Results posted on

2023-06-26

Participant Flow

Subjects with HAE Type 1 or Type 2 were eligible for the study following assessment of data obtained from screening procedures, including demonstration of a minimum number of qualifying HAE attacks documented during a prospective run-in period of 14 to 56 days from the date of the screening visit. Randomization was stratified by the HAE attack rate over the period between screening and randomization (≥ 2 attacks per month vs. \< 2 attacks per month).

Participant milestones

Participant milestones
Measure	Treatment Group 1 (110 mg Berotralstat QD) Parts 1 and 2: two 55 mg capsules of berotralstat QD × 48 weeks. Part 3: 150 mg berotralstat QD.	Treatment Group 2 (150 mg Berotralstat QD) Parts 1 and 2: two 75 mg capsules of berotralstat QD × 48 weeks. Part 3: 150 mg berotralstat QD.	Treatment Group 3a Subjects were treated with placebo in Part 1 and 110 mg berotralstat in part 2. In part 3 subjects were treated with 150 mg berotralstat QD.	Treatment Group 3b Subjects were treated with placebo in Part 1 and 150 mg berotralstat QD in part 2 and 3.
Part 1 STARTED	41	40	20	20
Part 1 COMPLETED	37	37	17	17
Part 1 NOT COMPLETED	4	3	3	3
Part 2 STARTED	37	37	17	17
Part 2 COMPLETED	28	31	15	14
Part 2 NOT COMPLETED	9	6	2	3
Part 3 STARTED	26	26	15	14
Part 3 COMPLETED	7	4	5	4
Part 3 NOT COMPLETED	19	22	10	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Group 1 (110 mg Berotralstat QD) Parts 1 and 2: two 55 mg capsules of berotralstat QD × 48 weeks. Part 3: 150 mg berotralstat QD.	Treatment Group 2 (150 mg Berotralstat QD) Parts 1 and 2: two 75 mg capsules of berotralstat QD × 48 weeks. Part 3: 150 mg berotralstat QD.	Treatment Group 3a Subjects were treated with placebo in Part 1 and 110 mg berotralstat in part 2. In part 3 subjects were treated with 150 mg berotralstat QD.	Treatment Group 3b Subjects were treated with placebo in Part 1 and 150 mg berotralstat QD in part 2 and 3.
Part 1 Perceived lack of efficacy	1	1	2	0
Part 1 Subject withdrew consent	0	1	0	1
Part 1 Lab abnormalities/AEs	3	1	1	0
Part 1 Withdrew Consent prior to dosing	0	0	0	1
Part 1 Other NOS	0	0	0	1
Part 2 Perceived lack of efficacy	5	3	0	2
Part 2 Subject withdrew consent	1	0	2	1
Part 2 Lab abnormalities/AEs	1	2	0	0
Part 2 Other NOS	0	1	0	0
Part 2 Intercurrent illness/new medical condition	1	0	0	0
Part 2 Investigator judgement	1	0	0	0
Part 3 Perceived lack of efficacy	2	2	2	0
Part 3 Subject withdrew consent	1	4	0	1
Part 3 Lab abnormalities/AEs	1	1	0	2
Part 3 Other NOS	1	1	0	0
Part 3 Intercurrent illness/new medical condition	0	1	1	0
Part 3 Sponsor discontinuation	1	0	0	0
Part 3 Berotralstat provided by alternative means	13	13	7	7

Baseline Characteristics

Safety Population. One subject from ITT population, randomised to the placebo group, was not dosed

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Berotralstat 110 mg Once Daily n=41 Participants Berotralstat administered as two 55mg capsules, orally QD for 24 weeks.	Part 1: Berotralstat 150 mg Once Daily n=40 Participants Berotralstat administered as two 75mg capsules, orally QD for 24 weeks.	Part 1: Placebo n=40 Participants Placebo administered as two 2 matching capsules, orally QD for 24 weeks.	Total n=121 Participants Total of all reporting groups
Age, Continuous	40.4 years STANDARD_DEVIATION 17.51 • n=41 Participants	40.0 years STANDARD_DEVIATION 13.98 • n=40 Participants	44.5 years STANDARD_DEVIATION 14.12 • n=40 Participants	41.6 years STANDARD_DEVIATION 15.32 • n=121 Participants
Sex: Female, Male Female	30 Participants n=41 Participants	23 Participants n=40 Participants	27 Participants n=40 Participants	80 Participants n=121 Participants
Sex: Female, Male Male	11 Participants n=41 Participants	17 Participants n=40 Participants	13 Participants n=40 Participants	41 Participants n=121 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=41 Participants	2 Participants n=40 Participants	1 Participants n=40 Participants	3 Participants n=121 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=41 Participants	38 Participants n=40 Participants	38 Participants n=40 Participants	115 Participants n=121 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=41 Participants	0 Participants n=40 Participants	1 Participants n=40 Participants	3 Participants n=121 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=41 Participants	0 Participants n=40 Participants	0 Participants n=40 Participants	0 Participants n=121 Participants
Race (NIH/OMB) Asian	1 Participants n=41 Participants	0 Participants n=40 Participants	0 Participants n=40 Participants	1 Participants n=121 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=41 Participants	0 Participants n=40 Participants	0 Participants n=40 Participants	0 Participants n=121 Participants
Race (NIH/OMB) Black or African American	2 Participants n=41 Participants	1 Participants n=40 Participants	2 Participants n=40 Participants	5 Participants n=121 Participants
Race (NIH/OMB) White	38 Participants n=41 Participants	38 Participants n=40 Participants	37 Participants n=40 Participants	113 Participants n=121 Participants
Race (NIH/OMB) More than one race	0 Participants n=41 Participants	1 Participants n=40 Participants	1 Participants n=40 Participants	2 Participants n=121 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=41 Participants	0 Participants n=40 Participants	0 Participants n=40 Participants	0 Participants n=121 Participants
Region of Enrollment Canada	4 participants n=41 Participants	3 participants n=40 Participants	3 participants n=40 Participants	10 participants n=121 Participants
Region of Enrollment Austria	1 participants n=41 Participants	2 participants n=40 Participants	1 participants n=40 Participants	4 participants n=121 Participants
Region of Enrollment Romania	0 participants n=41 Participants	1 participants n=40 Participants	0 participants n=40 Participants	1 participants n=121 Participants
Region of Enrollment Hungary	2 participants n=41 Participants	0 participants n=40 Participants	0 participants n=40 Participants	2 participants n=121 Participants
Region of Enrollment United States	28 participants n=41 Participants	24 participants n=40 Participants	25 participants n=40 Participants	77 participants n=121 Participants
Region of Enrollment Czechia	2 participants n=41 Participants	3 participants n=40 Participants	3 participants n=40 Participants	8 participants n=121 Participants
Region of Enrollment North Macedonia	0 participants n=41 Participants	1 participants n=40 Participants	1 participants n=40 Participants	2 participants n=121 Participants
Region of Enrollment United Kingdom	1 participants n=41 Participants	4 participants n=40 Participants	2 participants n=40 Participants	7 participants n=121 Participants
Region of Enrollment France	2 participants n=41 Participants	0 participants n=40 Participants	1 participants n=40 Participants	3 participants n=121 Participants
Region of Enrollment Germany	1 participants n=41 Participants	2 participants n=40 Participants	2 participants n=40 Participants	5 participants n=121 Participants
Region of Enrollment Spain	0 participants n=41 Participants	0 participants n=40 Participants	2 participants n=40 Participants	2 participants n=121 Participants
Baseline Investigator-confirmed attack rate ≥ 2 HAE attacks/month	28 Participants n=41 Participants • Safety Population. One subject from ITT population, randomised to the placebo group, was not dosed	30 Participants n=40 Participants • Safety Population. One subject from ITT population, randomised to the placebo group, was not dosed	27 Participants n=39 Participants • Safety Population. One subject from ITT population, randomised to the placebo group, was not dosed	85 Participants n=120 Participants • Safety Population. One subject from ITT population, randomised to the placebo group, was not dosed
Baseline Investigator-confirmed attack rate < 2 HAE attacks/month	13 Participants n=41 Participants • Safety Population. One subject from ITT population, randomised to the placebo group, was not dosed	10 Participants n=40 Participants • Safety Population. One subject from ITT population, randomised to the placebo group, was not dosed	12 Participants n=39 Participants • Safety Population. One subject from ITT population, randomised to the placebo group, was not dosed	35 Participants n=120 Participants • Safety Population. One subject from ITT population, randomised to the placebo group, was not dosed

PRIMARY outcome

Timeframe: 24 weeks

Population: The intent to treat (ITT) population included all randomized subjects, regardless of whether study treatment was administered. This population was the primary population for the analysis of the efficacy and health outcomes data.

Outcome measures

Outcome measures
Measure	Part 2: 110mg Berotralstat n=41 Participants Subjects were treated with 110 mg berotralstat QD in part 2	Part 2: 150mg Berotralstat n=40 Participants Subjects were treated with 150 mg berotralstat QD in part 2	Placebo n=40 Participants Placebo administered as two matching capsules, orally QD for 24 weeks in Part 1.	Part 2: 150mg Berotralstat Following Placebo Subjects were treated with 150 mg berotralstat QD in part 2, following prior treatment with placebo in part 1.	Part 3: Berotralstat Subjects were treated with 150 mg berostralstat QD in part 3.
Part 1: The Rate of Investigator-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168)	1.65 HAE attack rate per 28 days	1.31 HAE attack rate per 28 days	2.35 HAE attack rate per 28 days	—	—

PRIMARY outcome

Timeframe: Part 2: 24 weeks (Days 169 to 337). Part 3: 48 weeks (Days 338 to 674).

Population: The safety population included all subjects who received at least 1 capsule of study treatment.

The safety data was assessed for the safety population, for subjects who entered Part 2 and Part 3, and includes TEAEs that began in Part 2 or 3, respectively, for these subjects. Safety data for Part 2 and Part 3 is combined to clearly show TEAEs occurring in subjects as the proceeded through the 2 study parts. TEAEs are defined as AEs that occurred on or after first dose of study treatment, whether in Part 1 or 2, and were assigned to the relevant treatment depending on when the TEAE began (Part 2 or Part 3 treatment). No statistical analysis was performed on this safety data.

Outcome measures

Outcome measures
Measure	Part 2: 110mg Berotralstat n=37 Participants Subjects were treated with 110 mg berotralstat QD in part 2	Part 2: 150mg Berotralstat n=17 Participants Subjects were treated with 150 mg berotralstat QD in part 2	Placebo n=37 Participants Placebo administered as two matching capsules, orally QD for 24 weeks in Part 1.	Part 2: 150mg Berotralstat Following Placebo n=17 Participants Subjects were treated with 150 mg berotralstat QD in part 2, following prior treatment with placebo in part 1.	Part 3: Berotralstat n=81 Participants Subjects were treated with 150 mg berostralstat QD in part 3.
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE TEAE	22 Participants	13 Participants	27 Participants	12 Participants	67 Participants
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE Drug-related TEAE	4 Participants	5 Participants	7 Participants	7 Participants	12 Participants
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE TESAE	0 Participants	0 Participants	1 Participants	1 Participants	7 Participants
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE TEAE leading to discontinuation of study drug	1 Participants	0 Participants	2 Participants	2 Participants	3 Participants
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE GI abdominal-related TEAE	5 Participants	4 Participants	10 Participants	9 Participants	18 Participants
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE Drug-related TESAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE DMID grade 3 or 4 TEAE	1 Participants	1 Participants	2 Participants	1 Participants	10 Participants
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE Drug-related DMID grade 3 or 4 TEAE	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE TEAE leading to interruption of study drug	0 Participants	1 Participants	2 Participants	1 Participants	5 Participants
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE Drug-related investigator-identified rash	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE GI abdominal-related TEAE -study drug discontinued	1 Participants	0 Participants	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change in Quality of Life, on a 1-100 scale, where higher scores indicate more impairment and a decrease (change with a negative value) in AE-QoL questionnaire scores indicates an improvement in the subject's QoL. The minimum clinically important difference (MCID) for the AE-QoL questionnaire is -6 (total score). The AE-QoL is only validated for adults; however, data were collected on all adult and adolescent study subjects.

Outcome measures

Outcome measures
Measure	Part 2: 110mg Berotralstat n=40 Participants Subjects were treated with 110 mg berotralstat QD in part 2	Part 2: 150mg Berotralstat n=38 Participants Subjects were treated with 150 mg berotralstat QD in part 2	Placebo n=36 Participants Placebo administered as two matching capsules, orally QD for 24 weeks in Part 1.	Part 2: 150mg Berotralstat Following Placebo Subjects were treated with 150 mg berotralstat QD in part 2, following prior treatment with placebo in part 1.	Part 3: Berotralstat Subjects were treated with 150 mg berostralstat QD in part 3.
Part 1: Change From Baseline in Angioedema Quality of Life Questionnaire at Week 24 (Total Score)	-12.46 AE-QoL Total Score Change from baseline Standard Error 2.530	-14.59 AE-QoL Total Score Change from baseline Standard Error 2.592	-9.69 AE-QoL Total Score Change from baseline Standard Error 2.643	—	—

SECONDARY outcome

Timeframe: 24 weeks

Population: The ITT population included all randomized subjects, regardless of whether study treatment was administered. This population was the primary population for the analysis of the efficacy and health outcomes data. Data were analyzed according to randomized treatment.

Assessment of proportion of days subjects had angioedema symptoms from expert-confirmed HAE attacks during Part 1.

Outcome measures

Outcome measures
Measure	Part 2: 110mg Berotralstat n=41 Participants Subjects were treated with 110 mg berotralstat QD in part 2	Part 2: 150mg Berotralstat n=40 Participants Subjects were treated with 150 mg berotralstat QD in part 2	Placebo n=40 Participants Placebo administered as two matching capsules, orally QD for 24 weeks in Part 1.	Part 2: 150mg Berotralstat Following Placebo Subjects were treated with 150 mg berotralstat QD in part 2, following prior treatment with placebo in part 1.	Part 3: Berotralstat Subjects were treated with 150 mg berostralstat QD in part 3.
Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks	0.134 Proportion days with angioedema symptoms Standard Error 0.0191	0.119 Proportion days with angioedema symptoms Standard Error 0.0194	0.197 Proportion days with angioedema symptoms Standard Error 0.0196	—	—

SECONDARY outcome

Timeframe: Day 8 through to 24 weeks (or or the last dose date/time in Part 1 + 24 hours for subjects who discontinued drug in Part 1)

The rate of expert-confirmed HAE attacks for the effective treatment period gives an analysis of the efficacy of active treatment after berotralstat had reached steady-state concentrations, given the effective half-life of 150 mg berotralstat in Study BCX7353-106 (Study 106) of 89 hours.

Outcome measures

Outcome measures
Measure	Part 2: 110mg Berotralstat n=41 Participants Subjects were treated with 110 mg berotralstat QD in part 2	Part 2: 150mg Berotralstat n=40 Participants Subjects were treated with 150 mg berotralstat QD in part 2	Placebo n=40 Participants Placebo administered as two matching capsules, orally QD for 24 weeks in Part 1.	Part 2: 150mg Berotralstat Following Placebo Subjects were treated with 150 mg berotralstat QD in part 2, following prior treatment with placebo in part 1.	Part 3: Berotralstat Subjects were treated with 150 mg berostralstat QD in part 3.
Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period	1.918 HAE attack rate per 28 days Standard Deviation 1.7345	1.552 HAE attack rate per 28 days Standard Deviation 1.6390	2.490 HAE attack rate per 28 days Standard Deviation 1.6135	—	—

SECONDARY outcome

Timeframe: 24 weeks (Days 169 to 337)

Monthly Attack Rate was defined as the total number of investigator-confirmed HAE attacks experienced during the treatment period adjusted for the length of a month (defined as 28 days) and the number of days the subject was on treatment during that month. The end of Month 6 was defined as the start of Part 2 treatment. Baseline investigator-confirmed attack rate was defined as the total number of investigator-confirmed HAE attacks experienced in the period between screening and first dose of study drug adjusted for the length of a month (defined as 28 days) and the number of days during that period.

Outcome measures

Outcome measures
Measure	Part 2: 110mg Berotralstat n=53 Participants Subjects were treated with 110 mg berotralstat QD in part 2	Part 2: 150mg Berotralstat n=51 Participants Subjects were treated with 150 mg berotralstat QD in part 2	Placebo Placebo administered as two matching capsules, orally QD for 24 weeks in Part 1.	Part 2: 150mg Berotralstat Following Placebo Subjects were treated with 150 mg berotralstat QD in part 2, following prior treatment with placebo in part 1.	Part 3: Berotralstat Subjects were treated with 150 mg berostralstat QD in part 3.
Part 2: To Assess the Effectiveness of Berotralstat Over a 24- to 48 Week Period Month 6	-1.383 HAE attack rate-change from baseline Standard Deviation 1.7289	-1.593 HAE attack rate-change from baseline Standard Deviation 1.6581	—	—	—
Part 2: To Assess the Effectiveness of Berotralstat Over a 24- to 48 Week Period Month 7	-1.229 HAE attack rate-change from baseline Standard Deviation 1.8158	-1.903 HAE attack rate-change from baseline Standard Deviation 1.7402	—	—	—
Part 2: To Assess the Effectiveness of Berotralstat Over a 24- to 48 Week Period Month 12	-1.543 HAE attack rate-change from baseline Standard Deviation 1.6539	-1.910 HAE attack rate-change from baseline Standard Deviation 1.5330	—	—	—

SECONDARY outcome

Timeframe: Up to 144 weeks

Population: The ITT population included all randomized subjects, regardless of study treatment administration. Subjects in the 2 berotralstat treatment arms included those previously treated with placebo in part 1; for these subjects, visits were adjusted according to the date of 1st dose of active treatment. The variation in number of subjects analysed at each study visit reflects subject withdrawal prior to study completion and the number of subjects completing the AE-QoL questionnaire.

Angioedema-specific QoL was assessed by the AE-QoL, consisting of 4 domains (i.e., functioning, fatigue/mood, fears/shame, and nutrition) and a total score. The AE-QoL scores range from 0 points (best QoL) to 100 points (worst QoL). A decrease (change with a negative value) in AE-QoL questionnaire scores indicates an improvement in the subject's QoL. The minimum clinically important difference (MCID) for the AE-QoL questionnaire is -6 (total score). The AE-QoL was completed by the subjects at each visit starting at baseline, and questions were answered with regard to the previous 28 days. For subjects who received active treatment following placebo, visits were adjusted according to the date of the first dose of active treatment.

Outcome measures

Outcome measures
Measure	Part 2: 110mg Berotralstat n=58 Participants Subjects were treated with 110 mg berotralstat QD in part 2	Part 2: 150mg Berotralstat n=55 Participants Subjects were treated with 150 mg berotralstat QD in part 2	Placebo n=39 Participants Placebo administered as two matching capsules, orally QD for 24 weeks in Part 1.	Part 2: 150mg Berotralstat Following Placebo Subjects were treated with 150 mg berotralstat QD in part 2, following prior treatment with placebo in part 1.	Part 3: Berotralstat Subjects were treated with 150 mg berostralstat QD in part 3.
To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks Week 18	-9.97 AE-QoL score - change from baseline Standard Deviation 16.809	-15.13 AE-QoL score - change from baseline Standard Deviation 14.946	-12.48 AE-QoL score - change from baseline Standard Deviation 19.752	—	—
To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks Week 24	-9.80 AE-QoL score - change from baseline Standard Deviation 16.145	-12.81 AE-QoL score - change from baseline Standard Deviation 19.181	-12.51 AE-QoL score - change from baseline Standard Deviation 20.371	—	—
To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks Week 48	-10.19 AE-QoL score - change from baseline Standard Deviation 14.128	-13.78 AE-QoL score - change from baseline Standard Deviation 16.219	—	—	—
To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks Week 72	-12.34 AE-QoL score - change from baseline Standard Deviation 16.909	-13.02 AE-QoL score - change from baseline Standard Deviation 16.276	—	—	—
To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks Week 96	-12.81 AE-QoL score - change from baseline Standard Deviation 16.593	-17.92 AE-QoL score - change from baseline Standard Deviation 17.161	—	—	—
To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks Week 120	-15.24 AE-QoL score - change from baseline Standard Deviation 18.026	-17.24 AE-QoL score - change from baseline Standard Deviation 14.943	—	—	—
To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks Week 144	-11.29 AE-QoL score - change from baseline Standard Deviation 17.165	-11.65 AE-QoL score - change from baseline Standard Deviation 16.558	—	—	—
To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks Week 4	-5.85 AE-QoL score - change from baseline Standard Deviation 15.478	-9.70 AE-QoL score - change from baseline Standard Deviation 15.346	-7.762 AE-QoL score - change from baseline Standard Deviation 15.098	—	—
To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks Week 8	-10.58 AE-QoL score - change from baseline Standard Deviation 15.968	-13.09 AE-QoL score - change from baseline Standard Deviation 19.064	-11.33 AE-QoL score - change from baseline Standard Deviation 16.732	—	—
To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks Week 12	-11.51 AE-QoL score - change from baseline Standard Deviation 14.354	-13.95 AE-QoL score - change from baseline Standard Deviation 17.652	-10.63 AE-QoL score - change from baseline Standard Deviation 18.376	—	—

SECONDARY outcome

Timeframe: Up to 144 weeks

The Treatment Satisfaction Questionnaire for Medication (TSQM) was completed by subjects at baseline and at each study visit until the end of the study. TSQM scores consisted of 14 items of which 13 items were made up of 3 specific scales (Effectiveness, Side Effects, and Convenience) and 1 global satisfaction scale (Global Satisfaction). At baseline, TSQM questionnaires were completed based on subject's satisfaction with usual medications. At all other time points for collection of TSQM, subjects were asked about their level of satisfaction or dissatisfaction with the study drug. Scales scores were calculated for each scale and were transformed into scores ranging from 0 to 100, with higher scores indicating higher satisfaction. TSQM score and corresponding change from baseline values were calculated at each visit. For subjects who received active treatment following placebo, visits were adjusted according to the date of the first dose of active treatment.

Outcome measures

Outcome measures
Measure	Part 2: 110mg Berotralstat n=57 Participants Subjects were treated with 110 mg berotralstat QD in part 2	Part 2: 150mg Berotralstat n=54 Participants Subjects were treated with 150 mg berotralstat QD in part 2	Placebo n=39 Participants Placebo administered as two matching capsules, orally QD for 24 weeks in Part 1.	Part 2: 150mg Berotralstat Following Placebo Subjects were treated with 150 mg berotralstat QD in part 2, following prior treatment with placebo in part 1.	Part 3: Berotralstat Subjects were treated with 150 mg berostralstat QD in part 3.
To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks Week 4	-1.3 TSQM Global score - change from baseline Standard Deviation 31.75	2.4 TSQM Global score - change from baseline Standard Deviation 31.91	-18.1 TSQM Global score - change from baseline Standard Deviation 35.44	—	—
To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks Week 8	4.3 TSQM Global score - change from baseline Standard Deviation 31.51	2.1 TSQM Global score - change from baseline Standard Deviation 31.66	-19.2 TSQM Global score - change from baseline Standard Deviation 40.41	—	—
To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks Week 12	4.4 TSQM Global score - change from baseline Standard Deviation 33.03	4.3 TSQM Global score - change from baseline Standard Deviation 31.32	-21.1 TSQM Global score - change from baseline Standard Deviation 44.15	—	—
To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks Week 18	-1.8 TSQM Global score - change from baseline Standard Deviation 33.02	-3.8 TSQM Global score - change from baseline Standard Deviation 32.69	-18.9 TSQM Global score - change from baseline Standard Deviation 39.59	—	—
To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks Week 24	3.1 TSQM Global score - change from baseline Standard Deviation 33.69	2.9 TSQM Global score - change from baseline Standard Deviation 33.96	-20.8 TSQM Global score - change from baseline Standard Deviation 42.52	—	—
To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks Week 48	5.4 TSQM Global score - change from baseline Standard Deviation 31.52	6.7 TSQM Global score - change from baseline Standard Deviation 28.87	—	—	—
To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks Week 72	11.0 TSQM Global score - change from baseline Standard Deviation 30.43	10.9 TSQM Global score - change from baseline Standard Deviation 22.88	—	—	—
To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks Week 96	13.9 TSQM Global score - change from baseline Standard Deviation 30.16	14.5 TSQM Global score - change from baseline Standard Deviation 22.31	—	—	—
To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks Week 120	12.7 TSQM Global score - change from baseline Standard Deviation 29.55	14.6 TSQM Global score - change from baseline Standard Deviation 20.75	—	—	—
To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks Week 144	4.5 TSQM Global score - change from baseline Standard Deviation 39.11	8.7 TSQM Global score - change from baseline Standard Deviation 22.79	—	—	—

Adverse Events

Berotralstat 110mg Once Daily

Serious events: 5 serious events

Other events: 56 other events

Deaths: 0 deaths

Berotralstat 150mg Once Daily

Serious events: 5 serious events

Other events: 53 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Berotralstat 110mg Once Daily n=58 participants at risk；n=57 participants at risk Berotralstat administered as either two 55mg capsules, orally QD	Berotralstat 150mg Once Daily n=57 participants at risk；n=58 participants at risk Berotralstat administered as either two 75mg capsules, orally QD	Placebo n=39 participants at risk Placebo administered as two 2 matching capsules, orally QD
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	1.8% 1/57 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/58 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/39 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/57 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	1.7% 1/58 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/39 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.00% 0/57 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/58 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	2.6% 1/39 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Infections and infestations Pneumonia	1.8% 1/57 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/58 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	2.6% 1/39 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Nervous system disorders Transient ischaemic attack	0.00% 0/57 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/58 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	2.6% 1/39 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Investigations Medical observation	0.00% 0/57 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	1.7% 1/58 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/39 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Cardiac disorders Acute myocardial infarction	0.00% 0/57 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	1.7% 1/58 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/39 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.8% 1/57 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/58 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/39 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Nervous system disorders Syncope	0.00% 0/57 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	1.7% 1/58 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/39 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
General disorders Vascular stent occlusion	0.00% 0/57 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	1.7% 1/58 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/39 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Psychiatric disorders Bipolar disorder	1.8% 1/57 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/58 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/39 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Gastrointestinal disorders Gastritis alcoholic	1.8% 1/57 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/58 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/39 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Metabolism and nutrition disorders Obesity	1.8% 1/57 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/58 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/39 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.
Infections and infestations Pyelonephritis	0.00% 0/57 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	1.7% 1/58 • Number of events 1 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.	0.00% 0/39 • Adverse Events (AEs) were assessed and recorded from the time that the Informed consent form was signed through the last follow-up visit, approximately 3 weeks following the last dose of study drug, or until the AE was resolved or the subject was in a clinically stable condition with regards to the AE. AE data is presented for patients from the Safety Population; i.e. those who received at least one dose of study drug. AEs were assigned to the relevant treatment (i.e., 110 mg berotralstat, 150 mg berotralstat, placebo) depending on when the AE began relative study drug administration.

Other adverse events

Additional Information

Study Director

BioCryst Pharmaceuticals Inc

Phone: +1 919-859-1302

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place