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

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

Detailed Description
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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.

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

Conditions
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Hereditary Angioedema (HAE)

Intervention / Treatment
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* Drug: Icatibant (30 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Icatibant (30 mg)<br>30mg dose of icatibant is administered as a single subcutaneous injection in the abdominal area | Drug: Icatibant (30 mg)<br>* 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<br>* Other names: Firazyr;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | Over 48 hours post-dose | 
| Total Body Clearance (CL/F) of Icatibant | The rate at which a drug is removed from the body. | 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. | Over 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Total Number of Treatment-Emergent Adverse Events | Treatment-emergent adverse events (TEAEs) were those that started after the single dose of icatibant. | 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. |  | Over 48 hours post-dose | 
| Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results |  | Over 48 hours post-dose | 
| Change From Baseline in Diastolic Blood Pressure |  | Over 48 hours post-dose | 
| Change From Baseline in Systolic Blood Pressure |  | Over 48 hours post-dose | 
| Change From Baseline in Pulse Rate |  | Over 48 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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, Anti-Inflammatory Agents, Therapeutic Uses, Antirheumatic Agents, Adrenergic beta-Antagonists, Adrenergic Antagonists, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Central Nervous System Agents