A Pharmacokinetic, Tolerability and Safety Study of Icatibant in Children and Adolescents With Hereditary Angioedema

Study HGT-FIR-086 will enroll 30 subjects from 2 to less than 18 years of age, divided into 2
groups: prepubertal and pubertal/postpubertal. At least 10 prepubertal children and at least
20 adolescents (including 10 treated during a HAE attack) must be enrolled in the study.

After a qualifying screening period, the PK, safety/tolerability, and efficacy of treatment
with SC icatibant will be evaluated in at least 20 subjects (10 prepubertal and 10
pubertal/postpubertal subjects) who present with cutaneous, abdominal, or laryngeal symptoms
of an acute attack of HAE. The PK and safety/tolerability of SC icatibant will be evaluated
in at least 10 additional pubertal/postpubertal subjects who meet screening criteria and
receive treatment with SC icatibant in the absence of a current acute HAE attack.

The planned duration of active participation for subjects who present with an initial attack
of acute HAE will consist of treatment with a single subcutaneous injection of icatibant on
Day 1 through follow up at day 90.

After having received initial treatment with icatibant, either during or in the absence of an
attack, at least 10 pubertal/postpubertal subjects who subsequently experience an acute HAE
attack may continue to receive treatment with icatibant as a single SC administration per
attack for a total of 3 eligible icatibant-treated attacks.

The period of active participation in the study for prepubertal subjects will be
approximately 90 days, while that for pubertal/postpubertal subjects could be a maximum of
approximately 270 or 360 days (3 separate active periods of approximately 90 days for those
treated with icatibant during an attack; 4 separate active periods for those treated without
an attack), with each active period separated by periods of inactive participation of
variable duration.

Inclusion Criteria:

1. Two through <18 years of age at the time of first HAE attack.

- Prepubertal and pubertal/postpubertal subjects experiencing and acute cutaneous,
abdominal, or laryngeal HAE attack treated with icatibant as part of this study.

- Pubertal/postpubertal subjects with HAE who are treated with icatibant, but not
during an attack.

2. Documented diagnosis of HAE Type I or II.

3. Informed consent (and subject assent as appropriate) signed by the subject's
parent(s)or legal guardian(s).

Exclusion Criteria:

1. Diagnosis of angioedema other than HAE.

2. Participation in another clinical trial that involves the use of any investigational
product (drug or device)within 30 days prior to study enrollment or at any time during
the study.

3. Any known factor/disease that might interfere with the treatment compliance, study
conduct,or result interpretation.

4. Congenital or acquired cardiac anomalies that interfere significantly with cardiac
function.

5. Treatment with ACE inhibitors within 7 days prior to treatment.

6. Use of hormonal contraception within the 90 days prior to treatment.

7. Androgen use (eg, stanozolol, danazol, oxandrolone, methyltestosterone, testosterone)
within the 90 days prior to treatment.

8. Pregnancy or breastfeeding.

9. A physical condition that interferes with pubertal status determination.