Clinical trial NCT02045264: Open-label, Single-arm Study to Assess the Pharmacokinetics, Safety, and Tolerability of a Single Subcutaneous Dose of Icatibant in Healthy Japanese Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hereditary Angioedema (HAE)
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
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
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-01-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak Plasma Concentration (Cmax) of Icatibant and Metabolites
timeFrame: Over 48 hours post-dose
measure: Time to Peak Plasma Concentration (Tmax) of Icatibant and Metabolites
timeFrame: Over 48 hours post-dose
measure: Drug Concentration Half-Life (T1/2) of Icatibant and Metabolites
timeFrame: Over 48 hours post-dose
measure: Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Icatibant and Metabolites
timeFrame: Over 48 hours post-dose
measure: Total Body Clearance (CL/F) of Icatibant
timeFrame: Over 48 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Icatibant and Metabolites
timeFrame: Over 48 hours post-dose
Secondary outcomes:
measure: The Total Number of Treatment-Emergent Adverse Events
timeFrame: TEAEs were collected after the single dose of icatibant until follow up, 5-7 days after icatibant administration
measure: The Percentage of Subjects With Any Injection Site Reactions.
timeFrame: Over 48 hours post-dose
measure: Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results
timeFrame: Over 48 hours post-dose
measure: Change From Baseline in Diastolic Blood Pressure
timeFrame: Over 48 hours post-dose
measure: Change From Baseline in Systolic Blood Pressure
timeFrame: Over 48 hours post-dose
measure: Change From Baseline in Pulse Rate
timeFrame: Over 48 hours post-dose
Other outcomes:
Locations:
city: Glendale
country: United States
facility: PAREXEL
state: California
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: