Hereditary Angioedema (HAE)Phase 1NCT02045264

Open-label, Single-arm Study to Assess the Pharmacokinetics, Safety, and Tolerability of a Single Subcutaneous Dose of Icatibant in Healthy Japanese Volunteers

A Phase 1 study testing Icatibant (30 mg) in people with Hereditary Angioedema (HAE), run by Shire at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a single-dose study to evaluate the pharmacokinetics, safety, and tolerability of icatibant administered to adult Japanese subjects. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Hereditary Angioedema (HAE)
What is being tested?: Icatibant (30 mg)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited States
Study dates: 21 Feb 2014to 27 Feb 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy male and female volunteers, 18 to 55 years of age, inclusive; healthy status defined as absence of clinically significant findings in medical history or screening assessments
Japanese; defined as born in Japan, lived outside of Japan for no more than 10 years, and having Japanese parents and Japanese maternal and paternal grandparents
Body mass index of 18 to 28 kg/m2, inclusive

Who cannot join

History of, or current, clinically significant disease and/or abnormalities
Smoking habit in excess of 5 cigarettes per day or the equivalent within 30 days of Day 1 or inability to refrain from smoking during the study confinement period
Subject has current abnormal thyroid function, as defined as abnormal screening thyroid stimulating hormone (TSH) and free thyroxine (T4). Treatment with a stable dose of thyroid medication for at least 12 weeks is permitted
History of drug allergy or other allergy that, in the opinion of the investigator, contraindicates participation
Male subjects who consume more than 21 units of alcohol per week or 3 units per day. Female subjects who consume more than 14 units of alcohol per week or 2 units per day. (1 alcohol unit =1 beer or =1 wine (5oz/150mL) or =1 liquor (1.5oz/40mL) or =0.75oz alcohol)
Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. (1 caffeine unit is contained in the following items: one 6oz (180mL) cup of coffee, two 12oz (360mL) cans of cola, one 12oz cup of tea, three 1oz (85g) chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine)
Current use of any medication (including over-the-counter, herbal, or homeopathic preparations) with the exception of female hormonal replacement therapy or hormonal contraceptives. Occasional use of over-the-counter doses of ibuprofen or acetaminophen for minor self-limited pain (eg, headaches) is also acceptable. Current use is defined as use within 7 days of the first dose of investigational product\
Pregnant or lactating females

Trial locations and contacts

1 site in 1 country.

United States1 site

PAREXEL
Glendale, California, 91206

Other trials in United States

About this study

Official title: An Open-label, Single-arm Study to Assess the Pharmacokinetics, Safety, and Tolerability of a Single Subcutaneous Dose of Icatibant in Healthy Japanese Volunteers

This is a single-dose study to evaluate the pharmacokinetics, safety, and tolerability of icatibant administered to adult Japanese subjects.

Read the detailed description

Icatibant has been studied for the treatment of acute attacks of hereditary angioedema (HAE), an autosomal dominant disorder characterized by recurrent and self-limiting episodes of edema of the skin, larynx, and gastrointestinal tract. The most serious manifestation of an HAE attack is laryngeal edema, causing obstruction of the upper airways that may lead to death by asphyxiation if undiagnosed and/or untreated.

Icatibant has been approved in over 40 countries around the world including the United States (US) and Europe for the treatment of acute attacks of hereditary angioedema (HAE) in adults. This study is being conducted to evaluate the safety and tolerability of icatibant in a Japanese population and to evaluate whether race/ethnicity impacts the pharmacokinetics of icatibant after single subcutaneous injection.

This is an open-label, single-arm study that will enroll at least 12 Japanese subjects (in order to have 12 subjects complete the study), age 18-55 years inclusive. All subjects will receive a single subcutaneous injection of 30mg icatibant. The study will be conducted at 1 site in the US. The study will consist of a Screening Period, a Treatment Period, and a Follow-Up Period.

Conditions: Hereditary Angioedema (HAE)
Being tested: Icatibant (30 mg)
Keywords: Firazyr, Angioedema, Angioedemas, Hereditary, Vascular Diseases, Cardiovascular Diseases, Urticaria, Skin Diseases, Vascular, Skin Diseases, Hypersensitivity, Immediate, Hypersensitivity, Immune System Diseases, Genetic Diseases, Inborn, Icatibant, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Pharmacologic Actions
Medical subject headings: Angioedemas, Hereditary, Angioedema, Vascular Diseases, Cardiovascular Diseases, Urticaria, Skin Diseases, Vascular, Skin Diseases, Hypersensitivity, Immediate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Icatibant (30 mg)Drug
Also called Firazyr
On Day 1, subjects will receive a single 30mg subcutaneous injection of icatibant in their abdominal area. Subjects will be discharged from the study on Day 3 after collection of study related assessments

Study groups in NCT02045264
Study group	Role	What they receive
Icatibant (30 mg)	Experimental	30mg dose of icatibant is administered as a single subcutaneous injection in the abdominal area Receives: Drug: Icatibant (30 mg)

What is being measured

The primary outcome is the main question the study is designed to answer.

Peak Plasma Concentration (Cmax) of Icatibant and Metabolites
Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.
Measured: Over 48 hours post-dose
Time to Peak Plasma Concentration (Tmax) of Icatibant and Metabolites
Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached.
Measured: Over 48 hours post-dose
Drug Concentration Half-Life (T1/2) of Icatibant and Metabolites
The time it takes for the blood plasma concentration of a substance to halve.
Measured: Over 48 hours post-dose
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Icatibant and Metabolites
AUCinf is the area under the plasma concentration versus time curve extrapolated from time 0 to infinity, calculated using the observed value of the last non-zero concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Measured: Over 48 hours post-dose
Total Body Clearance (CL/F) of Icatibant
The rate at which a drug is removed from the body.
Measured: Over 48 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Icatibant and Metabolites
AUC0-t is the area under the plasma concentration versus time curve extrapolated from time 0 to to the last quantifiable concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Measured: Over 48 hours post-dose

Secondary outcomes (6)

The Total Number of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) were those that started after the single dose of icatibant.
Measured: TEAEs were collected after the single dose of icatibant until follow up, 5-7 days after icatibant administration
The Percentage of Subjects With Any Injection Site Reactions.
Measured: Over 48 hours post-dose
Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results
Measured: Over 48 hours post-dose
Change From Baseline in Diastolic Blood Pressure
Measured: Over 48 hours post-dose
Change From Baseline in Systolic Blood Pressure
Measured: Over 48 hours post-dose
Change From Baseline in Pulse Rate
Measured: Over 48 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Feb 201427 Feb 2014

First posted24 Jan 2014 (estimated)
Study start21 Feb 2014
Primary completion27 Feb 2014
Study completion27 Feb 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hereditary Angioedema (HAE)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02045264
Sponsor's protocol ID: SHP-FIR-101
Status last verified: May 2021
First submitted: 13 Jan 2014
Last updated: 3 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
Donidalorsen Treatment in Children With Hereditary Angioedema
Hereditary Angioedema (HAE)
RecruitingObservational study
A Study of Takhzyro in Teenagers and Adults With Hereditary Angioedema (HAE) in South Korea
Hereditary Angioedema (HAE)
Active, not recruitingPhase 3
HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE)
Hereditary Angioedema
RecruitingPhase 3
Study of IV Human Plasma-derived C1 Esterase Inhibitor Concentrate in Patients With Congenital C1-INH Deficiency for Treatment and Pre-procedure Preventing of Acute Hereditary Angioedema Attacks
Acute Hereditary Angio Edema
Active, not recruitingPhase 1/2
NTLA-2002 in Adults With Hereditary Angioedema (HAE)
Hereditary Angioedema

All Hereditary Angioedema (HAE) trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Single-arm Study to Assess the Pharmacokinetics, Safety, and Tolerability of a Single Subcutaneous Dose of Icatibant in Healthy Japanese Volunteers
ClinicalTrials.gov ID: NCT02045264
Acronym / sponsor ID: SHP-FIR-101
Conditions: Hereditary Angioedema (HAE)
Keywords: Firazyr, Angioedema, Angioedemas, Hereditary, Vascular Diseases, Cardiovascular Diseases, Urticaria, Skin Diseases, Vascular, Skin Diseases
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: ShireIndustry (pharma, biotech, devices)
Study start: 21 Feb 2014 (actual)
Primary completion: 27 Feb 2014 (actual)
Study completion: 27 Feb 2014 (actual)
First posted: 24 Jan 2014 (estimated)
Results: Posted 14 Jan 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This is a single-dose study to evaluate the pharmacokinetics, safety, and tolerability of icatibant administered to adult Japanese subjects.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Icatibant (30 mg)	Experimental	Drug: Icatibant (30 mg)30mg dose of icatibant is administered as a single subcutaneous injection in the abdominal area

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

Healthy male and female volunteers, 18 to 55 years of age, inclusive; healthy status defined as absence of clinically significant findings in medical history or screening assessments
Japanese; defined as born in Japan, lived outside of Japan for no more than 10 years, and having Japanese parents and Japanese maternal and paternal grandparents
Body mass index of 18 to 28 kg/m2, inclusive

Key exclusion criteria (8 listed)

History of, or current, clinically significant disease and/or abnormalities
Smoking habit in excess of 5 cigarettes per day or the equivalent within 30 days of Day 1 or inability to refrain from smoking during the study confinement period
Subject has current abnormal thyroid function, as defined as abnormal screening thyroid stimulating hormone (TSH) and free thyroxine (T4). Treatment with a stable dose of thyroid medication for at least 12 weeks is permitted
History of drug allergy or other allergy that, in the opinion of the investigator, contraindicates participation
Male subjects who consume more than 21 units of alcohol per week or 3 units per day. Female subjects who consume more than 14 units of alcohol per week or 2 units per day. (1 alcohol unit =1 beer or =1 wine (5oz/150mL) or =1 liquor (1.5oz/40mL) or =0.75oz alcohol)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Icatibant (30 mg)Also: FirazyrOn Day 1, subjects will receive a single 30mg subcutaneous injection of icatibant in their abdominal area. Subjects will be discharged from the study on Day 3 after collection of study related assessments	Drug	Icatibant (30 mg)

Primary outcome

Peak Plasma Concentration (Cmax) of Icatibant and Metabolites
Time frame: Over 48 hours post-dose
Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.
Time to Peak Plasma Concentration (Tmax) of Icatibant and Metabolites
Time frame: Over 48 hours post-dose
Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached.
Drug Concentration Half-Life (T1/2) of Icatibant and Metabolites
Time frame: Over 48 hours post-dose
The time it takes for the blood plasma concentration of a substance to halve.
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Icatibant and Metabolites
Time frame: Over 48 hours post-dose
AUCinf is the area under the plasma concentration versus time curve extrapolated from time 0 to infinity, calculated using the observed value of the last non-zero concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Total Body Clearance (CL/F) of Icatibant
Time frame: Over 48 hours post-dose
The rate at which a drug is removed from the body.
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Icatibant and Metabolites
Time frame: Over 48 hours post-dose
AUC0-t is the area under the plasma concentration versus time curve extrapolated from time 0 to to the last quantifiable concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.

6 secondary outcomes

The Total Number of Treatment-Emergent Adverse Events
Time frame: TEAEs were collected after the single dose of icatibant until follow up, 5-7 days after icatibant administration
The Percentage of Subjects With Any Injection Site Reactions.
Time frame: Over 48 hours post-dose
Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results
Time frame: Over 48 hours post-dose
Change From Baseline in Diastolic Blood Pressure
Time frame: Over 48 hours post-dose
Change From Baseline in Systolic Blood Pressure
Time frame: Over 48 hours post-dose
Change From Baseline in Pulse Rate
Time frame: Over 48 hours post-dose

Results and safety

Results posted to the registry on 14 Jan 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Icatibant (30 mg)	12	12

Primary outcome: Peak Plasma Concentration (Cmax) of Icatibant and Metabolites

Time frame: Over 48 hours post-dose. Mean (Standard Deviation). Unit: ng/mL

Measure	Icatibant (30 mg) n = 12
Icatibant	1190 (261)
Metabolite 1	340 (67.7)
Metabolite 2	365 (74.8)

Population analysed: The Pharmacokinetic Set consisted of all subjects who had taken the single dose of icatibant and for whom the primary pharmacokinetic data were considered sufficient and interpretable.

Primary outcome: Time to Peak Plasma Concentration (Tmax) of Icatibant and Metabolites

Time frame: Over 48 hours post-dose. Mean (Standard Deviation). Unit: hr

Measure	Icatibant (30 mg) n = 12
Icatibant	0.67 (0.20)
Metabolite 1	1.92 (0.289)
Metabolite 2	1.92 (0.289)

Primary outcome: Drug Concentration Half-Life (T1/2) of Icatibant and Metabolites

Time frame: Over 48 hours post-dose. Mean (Standard Deviation). Unit: hr

Measure	Icatibant (30 mg) n = 12
Icatibant	1.77 (0.356)
Metabolite 1	3.69 (0.579)
Metabolite 2	4.11 (1.01)

Primary outcome: Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Icatibant and Metabolites

Time frame: Over 48 hours post-dose. Mean (Standard Deviation). Unit: ng*hr/mL

Measure	Icatibant (30 mg) n = 12
Icatibant	2320 (403)
Metabolite 1	1750 (308)
Metabolite 2	1960 (346)

6 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Icatibant (30 mg)	0 of 12 (0%)	2 of 12 (16.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Hereditary Angioedema (HAE)

RecruitingPhase 3
Donidalorsen Treatment in Children With Hereditary Angioedema
Hereditary Angioedema (HAE)
RecruitingObservational study
A Study of Takhzyro in Teenagers and Adults With Hereditary Angioedema (HAE) in South Korea
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Active, not recruitingPhase 3
HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE)
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Active, not recruitingPhase 1/2
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Study Director study director

Takeda

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Icatibant (30 mg) in people with Hereditary Angioedema (HAE), run by Shire at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak Plasma Concentration (Cmax) of Icatibant and Metabolites (time frame: Over 48 hours post-dose). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02045264.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2021.