Bradykinin Receptor Blocker in ACE Inhibitor-associated Angioedema

People who take ACE inhibitors may develop angioedema, a condition that causes itchy and
painful swelling beneath the skin around the eyes, lips, tongue, throat, hands, or feet. In
severe cases, the throat may swell, obstructing the airway and leading to breathing
difficulty. ACE inhibitors prevent the breakdown of a natural chemical in the body called
bradykinin. Increased levels of bradykinin, which can cause swelling, may contribute to the
development of angioedema. Blocking bradykinin receptor cells prevents bradykinin from
initiating swelling and may lead to a possible decrease in angioedema symptoms. The purpose
of this study is to evaluate the effectiveness of HOE-140, a bradykinin receptor blocker, at
reducing symptoms in people with ACE inhibitor-associated angioedema.

This study will enroll people admitted to the emergency room or hospital who have a severe
case of ACE inhibitor-associated angioedema. Participants will be randomly assigned to
receive an injection of either HOE-140 or placebo. Initially, participants will undergo an
electrocardiogram to measure the electrical activity of the heart. Then blood pressure
measurements, blood collection, a physical exam to determine the extent and duration of
swelling, and photographs of the swelling will occur at 2, 4, 8, 16, and 24 hours following
the start of treatment. Questionnaires will be completed by study staff and participants to
assess changes in angioedema symptoms and the extent of swelling. Participants will remain
in the hospital for 24 to 48 hours, depending on the severity of their symptoms. Blood will
be collected at a follow-up visit that will occur 7 days after the resolution of angioedema
symptoms.

Inclusion Criteria:

- Ambulatory

- ACE inhibitor-associated angioedema, as defined as swelling of the lips, pharynx, or
face while taking an ACE inhibitor, no history of angioedema while not taking an ACE
inhibitor, and no evidence of abnormal C1 inhibitor concentration or abnormal
complement levels. People with possible cases of ACE inhibitor-associated bowel edema
will not be enrolled.

- If female, must be postmenopausal for at least 1 year prior to study entry, undergone
surgical sterilization, or willing to use an effective form of birth control and take
a pregnancy test daily for the duration of the study

Exclusion Criteria:

- Pregnant or breastfeeding

- Started taking birth control pills in the 6 months prior to study entry