Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?",were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?",were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

The adjusted attack rate was calculated as the number of adjusted attacks observed during a given period and standardized to number of attacks per month, where 1 month is defined as a 28-day (4 week) period.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?",were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. The duration of each participant-reported attack was calculated in hours, based on the start, and stop date and time of the adjusted attack (time the attack finished).

Adjusted attacks were assessed based on anatomical location. Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Anatomical locations were categorized as abdominal-only, non-abdominal peripheral, mixed, and laryngeal attacks.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Number of adjusted attacks treated with targeted HAE medications was assessed.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Proportion of adjusted attacks treated with targeted HAE medications was assessed.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc)?",were considered unique (attack began > 24 hours from the end of the prior attack),and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

The number of days with angioedema symptoms is the number of the days during the reporting period for which at least 1 symptom is reported during an adjusted HAE attack based on the start date and resolution date of an attack.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc)?",were considered unique (attack began > 24 hours from the end of the prior attack),and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

The proportion of days with angioedema symptoms was based on the number of days with reported symptoms and the number of days the participant was on treatment, where the number of days with angioedema symptoms is the number of the days during the reporting period for which at least 1 symptom is reported during an adjusted HAE attack based on the start date and resolution date of an attack.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. The severity was assessed by the parent/caregiver as negligible, mild, moderate or severe.

The total number of participants who discontinued the treatment due to perceived lack of efficacy of berotralstat were reported.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Number of adjusted attacks that required hospitalization or clinic visits are reported.

Participants received 96 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

Participants received 78 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

Total of all reporting groups

Participants received 108 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

Participants received 96 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

Participants received 78 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

AUC0-6 is the area under the plasma concentration-time curve from time 0 to 6 hours.

Pharmacokinetic (PK) population included participants in the safety population with at least 1 evaluable and quantifiable post dose PK sample obtained. Number of participants analyzed refers to the participants who were evaluable for this outcome measure. Per protocol, fewer serial PK samples were drawn in Cohort 4 participants to remain within acceptable ranges of blood draw volumes; hence, Cohort 4 participants were not included in the analysis of this PK parameter.

Ctrough is the concentration at the end of a dosing interval of berotralstat.

Pharmacokinetic (PK) population included participants in the safety population with at least 1 evaluable and quantifiable post dose PK sample obtained. Number of participants analyzed refers to the participants who were evaluable for this outcome measure.

Cmax is the maximum observed plasma concentration of berotralstat.

Pharmacokinetic (PK) population included participants in the safety population with at least 1 evaluable and quantifiable post dose PK sample obtained. Number of participants analyzed refers to the participants who were evaluable for this outcome measure. Per protocol, fewer serial PK samples were drawn in Cohort 4 participants to remain within acceptable ranges of blood draw volumes; hence, Cohort 4 participants were not included in the analysis of this PK parameter.

Tlast is the time of the last measurable concentration (Clast) of berotralstat collected over the sampling interval.

Pharmacokinetic (PK) population included participants in the safety population with at least 1 evaluable and quantifiable post dose PK sample obtained. Number of participants analyzed refers to the participants who were evaluable for this outcome measure. Per protocol, fewer serial PK samples were drawn in Cohort 4 participants to remain within acceptable ranges of blood draw volumes; hence, Cohort 4 participants were not included in the analysis of this PK parameter.

Tmax is the time taken to reach the maximum observed plasma concentration of berotralstat.

Pharmacokinetic (PK) population included participants in the safety population with at least 1 evaluable and quantifiable post dose PK sample obtained. Number of participants analyzed refers to the participants who were evaluable for this outcome measure. Per protocol, fewer serial PK samples were drawn in Cohort 4 participants to remain within acceptable ranges of blood draw volumes; hence, Cohort 4 participants were not included in the analysis of this PK parameter.

An adverse event (AE) is any untoward medical occurrence in a clinical study participant. No causal relationship with study drug or with the clinical study itself is implied. An AE could be an unfavorable and unintended sign, symptom (including an abnormal laboratory finding), syndrome, or illness that developed or worsened during the clinical study. A serious adverse event (SAE) is any untoward medical occurrence resulting in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or other medically important event. TEAEs are AEs that occurred on/after first dose of berotralstat through 30 days post discontinuation of study treatment.

The safety population included all participants who received at least 1 dose of berotralstat.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?",were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?",were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

The adjusted attack rate was calculated as the number of adjusted attacks observed during a given period and standardized to number of attacks per month, where 1 month is defined as a 28-day (4 week) period.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?",were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. The duration of each participant-reported attack was calculated in hours, based on the start, and stop date and time of the adjusted attack (time the attack finished).

Adjusted attacks were assessed based on anatomical location. Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Anatomical locations were categorized as abdominal-only, non-abdominal peripheral, mixed, and laryngeal attacks.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Number of adjusted attacks treated with targeted HAE medications was assessed.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Proportion of adjusted attacks treated with targeted HAE medications was assessed.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc)?",were considered unique (attack began > 24 hours from the end of the prior attack),and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

The number of days with angioedema symptoms is the number of the days during the reporting period for which at least 1 symptom is reported during an adjusted HAE attack based on the start date and resolution date of an attack.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc)?",were considered unique (attack began > 24 hours from the end of the prior attack),and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

The proportion of days with angioedema symptoms was based on the number of days with reported symptoms and the number of days the participant was on treatment, where the number of days with angioedema symptoms is the number of the days during the reporting period for which at least 1 symptom is reported during an adjusted HAE attack based on the start date and resolution date of an attack.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack. The severity was assessed by the parent/caregiver as negligible, mild, moderate or severe.

The total number of participants who discontinued the treatment due to perceived lack of efficacy of berotralstat were reported.

Adjusted attacks included at least 1 symptom of swelling, had a response of "no" to the diary question: "In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (that is, allergic reaction, viral cold etc.)?", were considered unique (attack began > 24 hours from the end of the prior attack), and if the entire adjusted attack was untreated, it had a duration of > 24 hours. Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Number of adjusted attacks that required hospitalization or clinic visits are reported.

Participants received 150 mg berotralstat capsule orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

Participants received 108 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

Participants received 96 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

Participants received 78 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.