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

Primary Purpose

Hereditary Angioedema (HAE)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Icatibant (30 mg)
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hereditary Angioedema (HAE) focused on measuring 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

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • PAREXEL

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Icatibant (30 mg)

Arm Description

30mg dose of icatibant is administered as a single subcutaneous injection in the abdominal area

Outcomes

Primary Outcome Measures

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.
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.
Drug Concentration Half-Life (T1/2) of Icatibant and Metabolites
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
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
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
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.

Secondary Outcome Measures

The Total Number of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) were those that started after the single dose of icatibant.
The Percentage of Subjects With Any Injection Site Reactions.
Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results
Change From Baseline in Diastolic Blood Pressure
Change From Baseline in Systolic Blood Pressure
Change From Baseline in Pulse Rate

Full Information

First Posted
January 13, 2014
Last Updated
May 13, 2021
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT02045264
Brief Title
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

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
February 21, 2014 (Actual)
Primary Completion Date
February 27, 2014 (Actual)
Study Completion Date
February 27, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Icatibant (30 mg)
Arm Type
Experimental
Arm Description
30mg dose of icatibant is administered as a single subcutaneous injection in the abdominal area
Intervention Type
Drug
Intervention Name(s)
Icatibant (30 mg)
Other Intervention Name(s)
Firazyr
Intervention Description
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
Primary Outcome Measure Information:
Title
Peak Plasma Concentration (Cmax) of Icatibant and Metabolites
Description
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 Frame
Over 48 hours post-dose
Title
Time to Peak Plasma Concentration (Tmax) of Icatibant and Metabolites
Description
Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached.
Time Frame
Over 48 hours post-dose
Title
Drug Concentration Half-Life (T1/2) of Icatibant and Metabolites
Description
The time it takes for the blood plasma concentration of a substance to halve.
Time Frame
Over 48 hours post-dose
Title
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Icatibant and Metabolites
Description
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.
Time Frame
Over 48 hours post-dose
Title
Total Body Clearance (CL/F) of Icatibant
Description
The rate at which a drug is removed from the body.
Time Frame
Over 48 hours post-dose
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Icatibant and Metabolites
Description
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.
Time Frame
Over 48 hours post-dose
Secondary Outcome Measure Information:
Title
The Total Number of Treatment-Emergent Adverse Events
Description
Treatment-emergent adverse events (TEAEs) were those that started after the single dose of icatibant.
Time Frame
TEAEs were collected after the single dose of icatibant until follow up, 5-7 days after icatibant administration
Title
The Percentage of Subjects With Any Injection Site Reactions.
Time Frame
Over 48 hours post-dose
Title
Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results
Time Frame
Over 48 hours post-dose
Title
Change From Baseline in Diastolic Blood Pressure
Time Frame
Over 48 hours post-dose
Title
Change From Baseline in Systolic Blood Pressure
Time Frame
Over 48 hours post-dose
Title
Change From Baseline in Pulse Rate
Time Frame
Over 48 hours post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
PAREXEL
City
Glendale
State/Province
California
ZIP/Postal Code
91206
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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