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

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.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema (HAE)
• Intervention / Treatment: Drug: Icatibant (30 mg)

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Parexel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. 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
3. Body mass index of 18 to 28 kg/m2, inclusive

Exclusion Criteria:

1. History of, or current, clinically significant disease and/or abnormalities
2. 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
3. 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
4. History of drug allergy or other allergy that, in the opinion of the investigator, contraindicates participation
5. 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)
6. 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)
7. 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\
8. Pregnant or lactating females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Icatibant (30 mg); 30mg dose of icatibant is administered as a single subcutaneous injection in the abdominal area	Drug: Icatibant (30 mg); 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; Other Names: Firazyr

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2014
• Primary Completion (Actual): February 27, 2014
• Study Completion (Actual): February 27, 2014

Study Registration Dates

• First Submitted: January 13, 2014
• First Submitted That Met QC Criteria: January 22, 2014
• First Posted (Estimate): January 24, 2014

Study Record Updates

• Last Update Posted (Actual): June 3, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Urticaria; Physiological Effects of Drugs; Central Nervous System Agents; Peripheral Nervous System Agents; Pharmacologic Actions; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Therapeutic Uses; Skin Diseases; Angioedema; Analgesics; Anti-Inflammatory Agents; Adrenergic beta-Antagonists; Neurotransmitter Agents; Angioedemas, Hereditary; Molecular Mechanisms of Pharmacological Action; Adrenergic Agents; Antirheumatic Agents; Adrenergic Antagonists; Analgesics, Non-Narcotic; Firazyr; Skin Diseases, Vascular; Icatibant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Bradykinin B2 Receptor Antagonists; Bradykinin Receptor Antagonists; Icatibant
• Other Study ID Numbers: SHP-FIR-101