E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
This is a rare medical condition where the
body has local swellings in various body parts including the hands, feet,
face and airway, (throat) caused by treatment with anti-hypertensive drugs. |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002424 |
E.1.2 | Term | Angioedema |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Efficacy Objective:
To compare the efficacy of icatibant with placebo in the treatment of angiotensinconverting enzyme inhibitor (ACE-I)-induced angioedema based on the Time to Meeting Discharge Criteria (TMDC) endpoint.
Primary Safety Objective:
To assess the safety and tolerability of icatibant treatment in patients experiencing an attack of ACE-I-induced angioedema.
|
|
E.2.2 | Secondary objectives of the trial |
Key Secondary Efficacy Objective:
To compare the efficacy of icatibant with placebo in the treatment of ACE-I-induced angioedema based on the Time to Onset of Symptom Relief (TOSR) endpoint.
Pharmacokinetic Objective:
To characterize the pharmacokinetic (PK) properties of icatibant and its major metabolites (M1 and M2 [amino acids 1-5 and amino acids 7-10, respectively]) in patients with ACEI-induced angioedema. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, 18 years of age or older.
2. Patient is currently being treated with an ACE inhibitor.
3. Patient presenting with an ACE inhibitor-induced angioedema attack of the head and/or neck region within 12 hours of onset (must be sufficiently less than 12 hours to allow study drug to be given with 12 hours of onset).
4. Angioedema must be considered at least moderate in severity for at least one of the four primary efficacy angioedema-associated upper airway symptoms (difficulty breathing, difficulty swallowing, voice changes, tongue swelling).
5. Patient must have voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient.
6. Females must have a negative urine pregnancy test prior to administration of the study medication, with the exception of those females who have had a total hysterectomy or bilateral oophorectomy, or who are 2 years post-menopausal. |
|
E.4 | Principal exclusion criteria |
1. Patient has a diagnosis of angioedema of other etiology (eg, hereditary or acquired angioedema, allergic angioedema [eg, food, insect bite or sting, evident clinical response to antihistamines and/or corticosteroids], anaphylaxis, trauma, abscess or
infection or associated disease, local inflammation, local tumor, post-operative or post-radiogenic edema, salivary gland disorders, other [non-ACE inhibitor] druginduced angioedema).
2. Patients with a family history of recurrent angioedema.
3. Patients who have had a previous episode(s) of angioedema while not on ACE inhibitor therapy.
4. Patients with acute urticaria (itchy, erythematous wheals).
5. Patients who have an intervention to support the airway (eg, intubation, tracheotomy, cricothyrotomy) due to the current attack of angioedema.
6. Patient has any of the following vascular conditions that, in the judgment of the investigator, would be a contraindication to participation in the study.
Unstable angina pectoris or acute myocardial ischemia.
Hypertensive urgency or emergency (diastolic blood pressure [DBP] >120 mm Hg or systolic blood pressure [SBP] >180 mm Hg).
Within 1 month of a stroke or transient ischemic attack.
New York Heart Association (NYHA) heart failure Class IV.
7. Patient has a serious or acute condition or illness that, in the judgment of the investigator, would interfere with evaluating the safety and/or efficacy assessments of the study.
8. Patient is pregnant or breast feeding.
9. Patient has participated in another investigational study in the past 30 days.
10. Patient is unable to understand the nature, scope, and possible consequences of the protocol, or is unlikely or unable to comply with the protocol assessments, or is unlikely to complete the study for any reason.
11. Patients who are not suitable for the study in the opinion of the investigator. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint:
Investigators will assess the severity of the following angioedema-associated upper airway symptoms: difficulty breathing, difficulty swallowing, voice changes, and tongue swelling. The assessment will be based on a 5-point severity scale from 0 (absent) to 4 (very severe). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, 0.5 hr, every hour up to 8 hrs.
During a stay longer than 8 hours in the emergency department or hospital, airway symptom assessments by the investigator will continue and be perfiormed every 2 hours from >8 to 24 hours and every 3 hours from >24 hours, until Time to Meeting Discharge Criteria (TMDC) endpoint has been met and the patient can be discharged. |
|
E.5.2 | Secondary end point(s) |
Safety Assessments:
The following safety assessments will be performed at the specified time points:
Physical examinations at baseline and at 8 hours after study drug administration. If the patient remains in the ED or hospital longer than 8 hours, an additional physical examination will be performed at discharge.
Vital signs including blood pressure at baseline and at 0.5, 1, 2, 4, 6 and 8 hours after study drug administration. If the patient remains in the ED or hospital longer than 8 hours, vital signs will be performed at 3-hour intervals and at discharge.
ECG at baseline and at 0.75 and 8 hours after study drug administration.
Serum chemistry and hematology blood tests, and urinalysis at baseline and at 8 hours after study drug administration.
Injection site reaction assessments at 0.5, 2, 4, and 8 hours after study drug
administration. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Israel |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |