Hereditary Angioedema (HAE)
Conditions
Keywords
Efficacy, Hereditary angioedema, HAE, Pediatric, Children, Pharmacokinetics, Safety, Firazyr, icatibant
Brief summary
HGT-FIR-086 is a multicenter, open-label, non-randomized, single-arm study to evaluate the Pharmacokinetics, tolerability,safety, and efficacy on reproductive hormones, of a single subcutaneous (SC) administration of icatibant in approximately 30 pediatric subjects with Hereditary Angioedema (HAE) during an initial acute attack.
Detailed description
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.
Interventions
DRUGicatibant
Single dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Changes in Reproductive Hormones | Pre-dose up to 97 days post-dose | Reproductive hormone levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone in females, and FSH, LH, and testosterone in males were measured. The number of participants with clinically significant changes in reproductive hormones was reported. |
| Total Plasma Clearance (CL/F) of a Single Subcutaneous (SC) Dose of Icatibant | Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1 | Total plasma clearance (CL/F) of a single SC dose of icatibant was reported. |
| Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4) of a Single Subcutaneous (SC) Dose of Icatibant | Pre-dose; 0.25, 0.5, 0.75, 1, 2, and 4 hours post-dose on Day 1 | Area under the plasma concentration-time curve from time zero to 4 hours post-dose (AUC0-4) of a single SC dose of icatibant was reported. |
| Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours Post-dose (AUC0-t) of a Single Subcutaneous (SC) Dose of Icatibant | Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1 | Area under the plasma concentration-time curve from time zero to 6 hours post-dose (AUC0-t) of a single SC dose of icatibant was reported. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of a Single Subcutaneous (SC) Dose of Icatibant | Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1 | Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of a single SC dose of icatibant was reported. |
| Volume of Distribution (Vz/F) of a Single Subcutaneous (SC) Dose of Icatibant | Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1 | Volume of distribution (Vz/F) of a single SC dose of icatibant was reported. |
| Elimination Half-life (t1/2) of a Single Subcutaneous (SC) Dose of Icatibant | Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1 | Elimination half-life (t1/2) of a single SC dose of icatibant was reported. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Pre-dose up to 97 days post-dose | Vital signs included pulse rate, blood pressure, respiration rate, and temperature. The number of participants who reported clinically significant changes in vital signs were reported. |
| Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) | 6 - 8 hours post-dose on Day 1 | A standard 12-lead ECG was performed after 10 minutes at rest when the participant was seated or supine following treatment. The number of participants who reported clinically significant changes in ECGs were reported. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Evaluations | Pre-dose up to 97 days post-dose | Clinical laboratory evaluations included clinical chemistry (including liver function tests), hematology, urinalysis. The number of participants who reported clinically significant changes in clinical laboratory evaluations were reported. |
| Number of Participants Who Reported Presence of Anti-icatibant Antibodies | Pre-dose up to 97 days post-dose | The number of participants who reported anti-icatibant antibodies were reported. |
| Number of Participants With Adverse Events (AEs) | From the start of study drug administration up to 97 days post-dose | An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in a clinical study, whether or not considered investigational product related. |
| Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1 | 1 h post-dose on Day 1 up to 9 days post-dose | The number of participants with injection site reactions (erythema, swelling, burning sensation, itching/pruritus, warm sensation, cutaneous pain, or other) that occured after initial icatibant administration was reported. |
| Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3 | 1 h post-dose up to 9 days post-dose | The number of participants with injection site reactions (erythema, swelling, burning sensation, itching/pruritus, warm sensation, cutaneous pain, or other) that occurred after subsequent icatibant administration by study-site personnel (health care practitioner \[HCP\] administration) or by caregiver/self (caregiver administration) was reported. In the below table, E-2 refers to icatibant exposure 2 and E-3 refers to icatibant exposure 3. |
| Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant | Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1 | Time to peak concentration (Tmax) of a single SC dose of icatibant was reported. |
| Maximum Plasma Concentration (Cmax) of a Single Subcutaneous (SC) Dose of Icatibant | Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1 | Maximum plasma concentration (Cmax) of a single SC dose of icatibant was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3 | From start of study drug administration up to 12 hours post-dose | The TOSR was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which there was at least a 20% improvement in the composite (or average) post-treatment symptom score with no worsening of any single component score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). TOSR for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported. |
| Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1 | From start of study drug administration up to 52 hours post-dose | The TOSR was defined as the earliest time at which the post-treatment score improved by at least one level. Participants of 4 years age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). TOSR for participants who received initial icatibant administration was reported. |
| Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3 | From start of study drug administration up to 28 hours post-dose | The TOSR was defined as the earliest time at which the post-treatment score improved by at least one level. Participants of 4 years age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). TOSR for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported. |
| Time to Onset of Symptom Relief (TOSR) for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores | From start of study drug administration up to 8.5 hours post-dose | The TOSR was defined as the earliest time at which a 20% improvement was seen in the total post-treatment score. Participants of 4 years age and younger underwent investigator assessment of HAE-related pain (cutaneous, abdominal, and laryngeal) using the FLACC comportmental pain scale. Each of the 5 categories was scored from 0 to 2. Face(F): 0 (no particular expression/smile) - 2 (frequent to constant frown clenched jaw quivering chin); Legs(L): 0 (normal position/relaxed) - 2 (kicking/legs drawn up); Activity(A): 0 (lying quietly, normal position, moves easily) - 2 (arched rigid/jerking); Cry(C): 0 (No cry \[awake/asleep\]) - 2 (crying steadily/screams/sobs or frequent complaints); Consolability(C): 0 (content/relaxed) - 2 (difficult to console/comfort), resulting in a total score between 0 and 10. |
| Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1 | From start of study drug administration up to 8.5 hours post-dose | Time to minimum symptom was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which all symptoms were either mild or absent for the investigator-reported symptom score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). Time to minimum symptom for participants who received initial icatibant administration was reported. |
| Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3 | From start of study drug administration up to 12 hours post-dose | Time to minimum symptom was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which all symptoms were either mild or absent for the investigator-reported symptom score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). Time to minimum symptom for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported. |
| Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1 | From start of study drug administration up to 52 hours post-dose | Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which post-treatment score improved to zero (or no pain). Participants of 4 years of age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). Time to minimum symptom for participants who received initial icatibant administration was reported. |
| Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3 | From start of study drug administration up to 28 hours post-dose | Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which post-treatment score improved to zero (or no pain). Participants of 4 years of age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). Time to minimum symptom for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported. |
| Time to Minimum Symptom for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores | From start of study drug administration up to 8.5 hours post-dose | Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which the total post-treatment score improved to zero. Participants of 4 years age and younger underwent investigator assessment of HAE-related pain (cutaneous, abdominal, and laryngeal) using the FLACC comportmental pain scale. Each of the 5 categories was scored from 0 to 2. (F) Face: 0 (no particular expression/smile) - 2 (frequent to constant frown clenched jaw quivering chin); (L) Legs: 0 (normal position/relaxed) - 2 (kicking/legs drawn up); (A) Activity: 0 (lying quietly, normal position, moves easily) - 2 (arched rigid/jerking); (C) Cry: 0 (No cry \[awake/asleep\]) - 2 (crying steadily/screams/sobs or frequent complaints); (C) Consolability: 0 (content/relaxed) - 2 (difficult to console/comfort), resulting in a total score between 0 and 10. |
| Time to Use of Rescue Medication for the Treatment of Symptoms of the Hereditary Angioedema (HAE) Attack Following Study Drug Administration | From the start of study drug administration up to 52 hours post-dose | Rescue medication was any medication used after the administration of icatibant which, in the opinion of the investigator, was immediately necessary to alleviate acute symptoms which are judged by the investigator as resultant from the current HAE attack. Time to first use of rescue medication prior to the onset of symptom relief was calculated from the time of study drug administration to the first use of rescue medication prior to the onset of symptom relief. This analysis was not performed since as per protocol, This analysis will only be performed if there are at least 5 participants for a given attack who used rescue medication prior to attaining symptom relief. |
| Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | From 2 hours post-dose to 4 hours post-dose | The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5- point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). The number of participants with a worsened severity of HAE symptoms at 4 hours post-dose from 2 hours postdose were reported. |
| Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | From 2 hours post-dose to 4 hours post-dose | The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5- point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). The number of participants with a worsened severity of HAE symptoms at 4 hours post-dose from 2 hours post-dose were reported. |
| Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1 | From start of study drug administration up to 8.5 hours post-dose | The TOSR was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which there was at least a 20 percent (%) improvement in the average post-treatment symptom score with no worsening of any single component score for the initial icatibant exposure. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of hereditary angioedema (HAE) using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). TOSR for participants who received initial icatibant administration was reported. |
Countries
Australia, Austria, Canada, Colombia, Germany, Hungary, Israel, Italy, Spain, United States
Participant flow
Recruitment details
The study was conducted at 27 study centers in the United States, Germany, Israel, Spain, Argentina, Australia, Austria, Canada, Colombia, Hungary, and Italy between 27 January 2012 (first participant first visit) and 12 March 2018 (last participant last visit).
Pre-assignment details
A total of 32 participants were enrolled and received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Prepubertal Participants received a single SC injection of 0.4 mg/kg icatibant (up to a maximal dose of 30 mg) in the abdominal region. | 11 |
| Pubertal/Postpubertal Participants received a SC injection of 0.4 mg/kg icatibant (up to a maximal dose of 30 mg) in the abdominal region and participants after receiving initial treatment with icatibant, who subsequently experienced an acute hereditary angioedema (HAE) attack continued to receive treatment with icatibant as a single SC administration per attack for a total of 3 eligible icatibant exposures. | 21 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Initial Icatibant Exposure | Lack of adherence and poor compliance | 0 | 3 |
| Initial Icatibant Exposure | Withdrawal by Subject | 0 | 9 |
Baseline characteristics
| Characteristic | Pubertal/Postpubertal | Total | Prepubertal |
|---|---|---|---|
| Age, Continuous | 14.3 Years STANDARD_DEVIATION 1.66 | 12.3 Years STANDARD_DEVIATION 3.48 | 8.6 Years STANDARD_DEVIATION 2.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 29 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 31 Participants | 11 Participants |
| Sex: Female, Male Female | 8 Participants | 13 Participants | 5 Participants |
| Sex: Female, Male Male | 13 Participants | 19 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 21 | 0 / 32 |
| other Total, other adverse events | 4 / 11 | 8 / 21 | 12 / 32 |
| serious Total, serious adverse events | 0 / 11 | 0 / 21 | 0 / 32 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4) of a Single Subcutaneous (SC) Dose of Icatibant
Area under the plasma concentration-time curve from time zero to 4 hours post-dose (AUC0-4) of a single SC dose of icatibant was reported.
Time frame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, and 4 hours post-dose on Day 1
Population: The PK population consisted of participants who were treated with icatibant and had sufficient icatibant plasma concentration time measurements to derive primary PK parameters. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prepubertal | Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4) of a Single Subcutaneous (SC) Dose of Icatibant | 1241 Hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 319 |
| Pubertal/Postpubertal: With Acute Attack | Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4) of a Single Subcutaneous (SC) Dose of Icatibant | 1448 Hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 304 |
| Pubertal/Postpubertal: Without Acute Attack | Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4) of a Single Subcutaneous (SC) Dose of Icatibant | 1335 Hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 211 |
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours Post-dose (AUC0-t) of a Single Subcutaneous (SC) Dose of Icatibant
Area under the plasma concentration-time curve from time zero to 6 hours post-dose (AUC0-t) of a single SC dose of icatibant was reported.
Time frame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Population: The PK population consisted of participants who were treated with icatibant and had sufficient icatibant plasma concentration time measurements to derive primary PK parameters. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prepubertal | Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours Post-dose (AUC0-t) of a Single Subcutaneous (SC) Dose of Icatibant | 1289 h*ng/mL | Standard Deviation 325 |
| Pubertal/Postpubertal: With Acute Attack | Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours Post-dose (AUC0-t) of a Single Subcutaneous (SC) Dose of Icatibant | 1573 h*ng/mL | Standard Deviation 372 |
| Pubertal/Postpubertal: Without Acute Attack | Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours Post-dose (AUC0-t) of a Single Subcutaneous (SC) Dose of Icatibant | 1398 h*ng/mL | Standard Deviation 225 |
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of a Single Subcutaneous (SC) Dose of Icatibant
Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of a single SC dose of icatibant was reported.
Time frame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Population: The PK population consisted of participants who were treated with icatibant and had sufficient icatibant plasma concentration time measurements to derive primary PK parameters. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prepubertal | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of a Single Subcutaneous (SC) Dose of Icatibant | 1243 h*ng/mL | Standard Deviation 244 |
| Pubertal/Postpubertal: With Acute Attack | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of a Single Subcutaneous (SC) Dose of Icatibant | 1710 h*ng/mL | Standard Deviation 569 |
| Pubertal/Postpubertal: Without Acute Attack | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of a Single Subcutaneous (SC) Dose of Icatibant | 1416 h*ng/mL | Standard Deviation 229 |
Primary
Elimination Half-life (t1/2) of a Single Subcutaneous (SC) Dose of Icatibant
Elimination half-life (t1/2) of a single SC dose of icatibant was reported.
Time frame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Population: The PK population consisted of participants who were treated with icatibant and had sufficient icatibant plasma concentration time measurements to derive primary PK parameters. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prepubertal | Elimination Half-life (t1/2) of a Single Subcutaneous (SC) Dose of Icatibant | 0.80 h | Standard Deviation 0.04 |
| Pubertal/Postpubertal: With Acute Attack | Elimination Half-life (t1/2) of a Single Subcutaneous (SC) Dose of Icatibant | 1.34 h | Standard Deviation 0.96 |
| Pubertal/Postpubertal: Without Acute Attack | Elimination Half-life (t1/2) of a Single Subcutaneous (SC) Dose of Icatibant | 0.90 h | Standard Deviation 0.1 |
Primary
Maximum Plasma Concentration (Cmax) of a Single Subcutaneous (SC) Dose of Icatibant
Maximum plasma concentration (Cmax) of a single SC dose of icatibant was reported.
Time frame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Population: The PK population consisted of participants who were treated with icatibant and had sufficient icatibant plasma concentration-time measurements to derive primary PK parameters. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prepubertal | Maximum Plasma Concentration (Cmax) of a Single Subcutaneous (SC) Dose of Icatibant | 659 Nanogram per milliliter (ng/mL) | Standard Deviation 158 |
| Pubertal/Postpubertal: With Acute Attack | Maximum Plasma Concentration (Cmax) of a Single Subcutaneous (SC) Dose of Icatibant | 805 Nanogram per milliliter (ng/mL) | Standard Deviation 125 |
| Pubertal/Postpubertal: Without Acute Attack | Maximum Plasma Concentration (Cmax) of a Single Subcutaneous (SC) Dose of Icatibant | 761 Nanogram per milliliter (ng/mL) | Standard Deviation 133 |
Primary
Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1
The number of participants with injection site reactions (erythema, swelling, burning sensation, itching/pruritus, warm sensation, cutaneous pain, or other) that occured after initial icatibant administration was reported.
Time frame: 1 h post-dose on Day 1 up to 9 days post-dose
Population: Safety population consisted of participants who were treated with icatibant at least once during the study. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prepubertal | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1 | Any Reaction | 9 Participants |
| Prepubertal | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1 | Any Severe Reaction | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1 | Any Reaction | 20 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1 | Any Severe Reaction | 2 Participants |
Primary
Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3
The number of participants with injection site reactions (erythema, swelling, burning sensation, itching/pruritus, warm sensation, cutaneous pain, or other) that occurred after subsequent icatibant administration by study-site personnel (health care practitioner \[HCP\] administration) or by caregiver/self (caregiver administration) was reported. In the below table, E-2 refers to icatibant exposure 2 and E-3 refers to icatibant exposure 3.
Time frame: 1 h post-dose up to 9 days post-dose
Population: Safety population consisted of participants who were treated with icatibant at least once during the study. Here the number of participants analyzed signifies participants who received subsequent icatibant exposures 2 and 3.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prepubertal | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3 | E-2: HCP Administration: Any Severe Reaction | 0 Participants |
| Prepubertal | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3 | E-2: HCP Administration: Any Reaction | 1 Participants |
| Prepubertal | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3 | E-2: Caregiver Administration: Any Reaction | 8 Participants |
| Prepubertal | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3 | E-2: Caregiver Administration: Any Severe Reaction | 3 Participants |
| Prepubertal | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3 | E-3: HCP Administration: Any Reaction | 1 Participants |
| Prepubertal | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3 | E-3: HCP Administration: Any Severe Reaction | 0 Participants |
| Prepubertal | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3 | E-3: Caregiver Administration: Any Reaction | 7 Participants |
| Prepubertal | Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3 | E-3: Caregiver Administration: Any Severe Reaction | 1 Participants |
Primary
Number of Participants Who Reported Presence of Anti-icatibant Antibodies
The number of participants who reported anti-icatibant antibodies were reported.
Time frame: Pre-dose up to 97 days post-dose
Population: Safety population consisted of participants who were treated with icatibant at least once during the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prepubertal | Number of Participants Who Reported Presence of Anti-icatibant Antibodies | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants Who Reported Presence of Anti-icatibant Antibodies | 0 Participants |
Primary
Number of Participants With Adverse Events (AEs)
An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in a clinical study, whether or not considered investigational product related.
Time frame: From the start of study drug administration up to 97 days post-dose
Population: Safety population consisted of participants who were treated with icatibant at least once during the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prepubertal | Number of Participants With Adverse Events (AEs) | 2 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Adverse Events (AEs) | 11 Participants |
Primary
Number of Participants With Clinically Significant Changes in Clinical Laboratory Evaluations
Clinical laboratory evaluations included clinical chemistry (including liver function tests), hematology, urinalysis. The number of participants who reported clinically significant changes in clinical laboratory evaluations were reported.
Time frame: Pre-dose up to 97 days post-dose
Population: Safety population consisted of participants who were treated with icatibant at least once during the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prepubertal | Number of Participants With Clinically Significant Changes in Clinical Laboratory Evaluations | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Clinically Significant Changes in Clinical Laboratory Evaluations | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs)
A standard 12-lead ECG was performed after 10 minutes at rest when the participant was seated or supine following treatment. The number of participants who reported clinically significant changes in ECGs were reported.
Time frame: 6 - 8 hours post-dose on Day 1
Population: Safety population consisted of participants who were treated with icatibant at least once during the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prepubertal | Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Reproductive Hormones
Reproductive hormone levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone in females, and FSH, LH, and testosterone in males were measured. The number of participants with clinically significant changes in reproductive hormones was reported.
Time frame: Pre-dose up to 97 days post-dose
Population: Safety population consisted of participants who were treated with icatibant at least once during the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prepubertal | Number of Participants With Clinically Significant Changes in Reproductive Hormones | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Clinically Significant Changes in Reproductive Hormones | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs included pulse rate, blood pressure, respiration rate, and temperature. The number of participants who reported clinically significant changes in vital signs were reported.
Time frame: Pre-dose up to 97 days post-dose
Population: Safety population consisted of participants who were treated with icatibant at least once during the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prepubertal | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Primary
Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant
Time to peak concentration (Tmax) of a single SC dose of icatibant was reported.
Time frame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Population: Pharmacokinetic (PK) population consisted of participants who were treated with icatibant and had sufficient icatibant plasma concentration-time measurements to derive primary PK parameters. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prepubertal | Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant | 0.42 Hour (h) | Standard Deviation 0.13 |
| Pubertal/Postpubertal: With Acute Attack | Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant | 0.55 Hour (h) | Standard Deviation 0.19 |
| Pubertal/Postpubertal: Without Acute Attack | Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant | 0.57 Hour (h) | Standard Deviation 0.17 |
Primary
Total Plasma Clearance (CL/F) of a Single Subcutaneous (SC) Dose of Icatibant
Total plasma clearance (CL/F) of a single SC dose of icatibant was reported.
Time frame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Population: The PK population consisted of participants who were treated with icatibant and had sufficient icatibant plasma concentration time measurements to derive primary PK parameters. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prepubertal | Total Plasma Clearance (CL/F) of a Single Subcutaneous (SC) Dose of Icatibant | 10.8 Milliliters per minute (mL/min) | Standard Deviation 4.63 |
| Pubertal/Postpubertal: With Acute Attack | Total Plasma Clearance (CL/F) of a Single Subcutaneous (SC) Dose of Icatibant | 13.1 Milliliters per minute (mL/min) | Standard Deviation 3.42 |
| Pubertal/Postpubertal: Without Acute Attack | Total Plasma Clearance (CL/F) of a Single Subcutaneous (SC) Dose of Icatibant | 19.3 Milliliters per minute (mL/min) | Standard Deviation 4.84 |
Primary
Volume of Distribution (Vz/F) of a Single Subcutaneous (SC) Dose of Icatibant
Volume of distribution (Vz/F) of a single SC dose of icatibant was reported.
Time frame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Population: The PK population consisted of participants who were treated with icatibant and had sufficient icatibant plasma concentration time measurements to derive primary PK parameters. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prepubertal | Volume of Distribution (Vz/F) of a Single Subcutaneous (SC) Dose of Icatibant | 12.5 Liters (L) | Standard Deviation 5.28 |
| Pubertal/Postpubertal: With Acute Attack | Volume of Distribution (Vz/F) of a Single Subcutaneous (SC) Dose of Icatibant | 23.5 Liters (L) | Standard Deviation 13.9 |
| Pubertal/Postpubertal: Without Acute Attack | Volume of Distribution (Vz/F) of a Single Subcutaneous (SC) Dose of Icatibant | 25.4 Liters (L) | Standard Deviation 8.87 |
Secondary
Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1
The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5- point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). The number of participants with a worsened severity of HAE symptoms at 4 hours post-dose from 2 hours postdose were reported.
Time frame: From 2 hours post-dose to 4 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. Here the number of participants analyzed signifies participants who evaluable for this endpoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Abdominal Tenderness | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Nausea | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Vomiting | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Diarrhea | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Skin Pain | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Erythema | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Skin Swelling | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Skin Irritation | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Skin Pain | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Abdominal Tenderness | 1 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Skin Swelling | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Erythema | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Vomiting | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Skin Irritation | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Diarrhea | 0 Participants |
| Pubertal/Postpubertal: With Acute Attack | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1 | Nausea | 0 Participants |
Secondary
Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3
The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5- point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). The number of participants with a worsened severity of HAE symptoms at 4 hours post-dose from 2 hours post-dose were reported.
Time frame: From 2 hours post-dose to 4 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. The number of participants analyzed signifies participants evaluable for this endpoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Abdominal Tenderness | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2:CA: Abdominal Tenderness | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Nausea | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: CA: Nausea | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2:HCPA: Vomiting | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: CA: Vomiting | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Diarrhea | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: CA: Diarrhea | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Skin Pain | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: CA: Skin Pain | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Erythema | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: CA: Erythema | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Skin Irritation | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: CA: Skin Irritation | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Skin Swelling | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: CA: Skin Swelling | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: CA: Dysphagia | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Voice Change | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Breathing Difficulties | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: CA: Breathing Difficulties | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Stridor | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: CA: Stridor | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Asphyxia | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2:CA: Asphyxia | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Abdominal Tenderness | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Abdominal Tenderness | 1 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Nausea | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Nausea | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Vomiting | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Vomiting | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Skin Pain | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Skin Pain | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Skin Irritation | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: HCPA: Dysphagia | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-2: CA: Voice Change | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Diarrhea | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Diarrhea | 1 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Erythema | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Erythema | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Skin Irritation | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Skin Swelling | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Skin Swelling | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Dysphagia | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Dysphagia | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Voice Change | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Voice Change | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Breathing Difficulties | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Breathing Difficulties | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Stridor | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Stridor | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: HCPA: Asphyxia | 0 Participants |
| Prepubertal | Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3 | E-3: CA: Asphyxia | 0 Participants |
Secondary
Time to Minimum Symptom for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores
Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which the total post-treatment score improved to zero. Participants of 4 years age and younger underwent investigator assessment of HAE-related pain (cutaneous, abdominal, and laryngeal) using the FLACC comportmental pain scale. Each of the 5 categories was scored from 0 to 2. (F) Face: 0 (no particular expression/smile) - 2 (frequent to constant frown clenched jaw quivering chin); (L) Legs: 0 (normal position/relaxed) - 2 (kicking/legs drawn up); (A) Activity: 0 (lying quietly, normal position, moves easily) - 2 (arched rigid/jerking); (C) Cry: 0 (No cry \[awake/asleep\]) - 2 (crying steadily/screams/sobs or frequent complaints); (C) Consolability: 0 (content/relaxed) - 2 (difficult to console/comfort), resulting in a total score between 0 and 10.
Time frame: From start of study drug administration up to 8.5 hours post-dose
Population: Participants from efficacy population with FLACC data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prepubertal | Time to Minimum Symptom for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores | 1.0 h |
Secondary
Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1
Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which post-treatment score improved to zero (or no pain). Participants of 4 years of age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). Time to minimum symptom for participants who received initial icatibant administration was reported.
Time frame: From start of study drug administration up to 52 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. Here the number of participants analyzed signifies participants with FPS-R data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prepubertal | Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1 | 2.4 h |
| Pubertal/Postpubertal: With Acute Attack | Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1 | 3.8 h |
Secondary
Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3
Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which post-treatment score improved to zero (or no pain). Participants of 4 years of age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). Time to minimum symptom for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported.
Time frame: From start of study drug administration up to 28 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. Here the number of participants analyzed signifies participants with FPS-R data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Prepubertal | Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-2: HCP Administration | 3.0 h |
| Prepubertal | Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-2: Caregiver Administration | 2.1 h |
| Prepubertal | Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-3: HCP Administration | 5.8 h |
| Prepubertal | Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-3:Caregiver Administration | 24.0 h |
Secondary
Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1
Time to minimum symptom was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which all symptoms were either mild or absent for the investigator-reported symptom score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). Time to minimum symptom for participants who received initial icatibant administration was reported.
Time frame: From start of study drug administration up to 8.5 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prepubertal | Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1 | 1.9 h |
| Pubertal/Postpubertal: With Acute Attack | Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1 | 1.0 h |
Secondary
Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3
Time to minimum symptom was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which all symptoms were either mild or absent for the investigator-reported symptom score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). Time to minimum symptom for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported.
Time frame: From start of study drug administration up to 12 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Prepubertal | Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-3: Caregiver Administration | 2.2 h |
| Prepubertal | Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-2: Caregiver Administration | 1.2 h |
| Unknown | Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-2: HCP Administration | — h |
| Unknown | Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-3: HCP Administration | — h |
Secondary
Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1
The TOSR was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which there was at least a 20 percent (%) improvement in the average post-treatment symptom score with no worsening of any single component score for the initial icatibant exposure. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of hereditary angioedema (HAE) using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). TOSR for participants who received initial icatibant administration was reported.
Time frame: From start of study drug administration up to 8.5 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prepubertal | Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1 | 1.0 h |
| Pubertal/Postpubertal: With Acute Attack | Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1 | 1.0 h |
Secondary
Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3
The TOSR was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which there was at least a 20% improvement in the composite (or average) post-treatment symptom score with no worsening of any single component score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). TOSR for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported.
Time frame: From start of study drug administration up to 12 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. Here the number of participants analyzed signifies participants who received subsequent icatibant exposures 2 and 3.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Prepubertal | Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-2: HCP Administration | 4.0 h |
| Prepubertal | Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-2: Caregiver Administration | 1.0 h |
| Prepubertal | Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-3: HCP Administration | 1.0 h |
| Prepubertal | Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-3:Caregiver Administration | 1.1 h |
Secondary
Time to Onset of Symptom Relief (TOSR) for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores
The TOSR was defined as the earliest time at which a 20% improvement was seen in the total post-treatment score. Participants of 4 years age and younger underwent investigator assessment of HAE-related pain (cutaneous, abdominal, and laryngeal) using the FLACC comportmental pain scale. Each of the 5 categories was scored from 0 to 2. Face(F): 0 (no particular expression/smile) - 2 (frequent to constant frown clenched jaw quivering chin); Legs(L): 0 (normal position/relaxed) - 2 (kicking/legs drawn up); Activity(A): 0 (lying quietly, normal position, moves easily) - 2 (arched rigid/jerking); Cry(C): 0 (No cry \[awake/asleep\]) - 2 (crying steadily/screams/sobs or frequent complaints); Consolability(C): 0 (content/relaxed) - 2 (difficult to console/comfort), resulting in a total score between 0 and 10.
Time frame: From start of study drug administration up to 8.5 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. Here the number of participants analyzed signifies participants of 4 years and younger with FLACC data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prepubertal | Time to Onset of Symptom Relief (TOSR) for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores | 1.0 h |
Secondary
Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1
The TOSR was defined as the earliest time at which the post-treatment score improved by at least one level. Participants of 4 years age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). TOSR for participants who received initial icatibant administration was reported.
Time frame: From start of study drug administration up to 52 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. Here the number of participants analyzed signifies participants with FPS-R data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prepubertal | Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1 | 0.9 h |
| Pubertal/Postpubertal: With Acute Attack | Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1 | 1.0 h |
Secondary
Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3
The TOSR was defined as the earliest time at which the post-treatment score improved by at least one level. Participants of 4 years age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). TOSR for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported.
Time frame: From start of study drug administration up to 28 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. Here the number of participants analyzed signifies participants with FPS-R data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Prepubertal | Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-2: HCP Administration | 3.0 h |
| Prepubertal | Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-2: Caregiver Administration | 1.0 h |
| Prepubertal | Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-3: HCP Administration | 1.0 h |
| Prepubertal | Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3 | Icatibant Exposure-3:Caregiver Administration | 1.1 h |
Secondary
Time to Use of Rescue Medication for the Treatment of Symptoms of the Hereditary Angioedema (HAE) Attack Following Study Drug Administration
Rescue medication was any medication used after the administration of icatibant which, in the opinion of the investigator, was immediately necessary to alleviate acute symptoms which are judged by the investigator as resultant from the current HAE attack. Time to first use of rescue medication prior to the onset of symptom relief was calculated from the time of study drug administration to the first use of rescue medication prior to the onset of symptom relief. This analysis was not performed since as per protocol, This analysis will only be performed if there are at least 5 participants for a given attack who used rescue medication prior to attaining symptom relief.
Time frame: From the start of study drug administration up to 52 hours post-dose
Population: Efficacy population consisted of participants who were treated with icatibant for their first and any additional attacks during the study. Here the number of participants analyzed signifies participants who were evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prepubertal | Time to Use of Rescue Medication for the Treatment of Symptoms of the Hereditary Angioedema (HAE) Attack Following Study Drug Administration | NA h |
| Pubertal/Postpubertal: With Acute Attack | Time to Use of Rescue Medication for the Treatment of Symptoms of the Hereditary Angioedema (HAE) Attack Following Study Drug Administration | NA h |