Trial Outcomes & Findings for Open-label, Single-arm Study to Assess the Pharmacokinetics, Safety, and Tolerability of a Single Subcutaneous Dose of Icatibant in Healthy Japanese Volunteers (NCT NCT02045264)

NCT ID: NCT02045264

Last Updated: 2021-06-03

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: Over 48 hours post-dose
• Results posted on: 2021-06-03

Participant Flow

Participant milestones

Measure	Icatibant (30 mg) Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	30.7 years STANDARD_DEVIATION 8.08 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Region of Enrollment United States	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Over 48 hours post-dose

Population: 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.

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.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Peak Plasma Concentration (Cmax) of Icatibant and Metabolites Icatibant	1190 ng/mL Standard Deviation 261
Peak Plasma Concentration (Cmax) of Icatibant and Metabolites Metabolite 1	340 ng/mL Standard Deviation 67.7
Peak Plasma Concentration (Cmax) of Icatibant and Metabolites Metabolite 2	365 ng/mL Standard Deviation 74.8

PRIMARY outcome

Timeframe: Over 48 hours post-dose

Population: 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.

Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Time to Peak Plasma Concentration (Tmax) of Icatibant and Metabolites Icatibant	0.67 hr Standard Deviation 0.20
Time to Peak Plasma Concentration (Tmax) of Icatibant and Metabolites Metabolite 1	1.92 hr Standard Deviation 0.289
Time to Peak Plasma Concentration (Tmax) of Icatibant and Metabolites Metabolite 2	1.92 hr Standard Deviation 0.289

PRIMARY outcome

Timeframe: Over 48 hours post-dose

Population: 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.

The time it takes for the blood plasma concentration of a substance to halve.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Drug Concentration Half-Life (T1/2) of Icatibant and Metabolites Icatibant	1.77 hr Standard Deviation 0.356
Drug Concentration Half-Life (T1/2) of Icatibant and Metabolites Metabolite 1	3.69 hr Standard Deviation 0.579
Drug Concentration Half-Life (T1/2) of Icatibant and Metabolites Metabolite 2	4.11 hr Standard Deviation 1.01

PRIMARY outcome

Timeframe: Over 48 hours post-dose

Population: 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.

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.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Icatibant and Metabolites Icatibant	2320 ng*hr/mL Standard Deviation 403
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Icatibant and Metabolites Metabolite 1	1750 ng*hr/mL Standard Deviation 308
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Icatibant and Metabolites Metabolite 2	1960 ng*hr/mL Standard Deviation 346

PRIMARY outcome

Timeframe: Over 48 hours post-dose

Population: 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.

The rate at which a drug is removed from the body.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Total Body Clearance (CL/F) of Icatibant	13200 mL/hr Standard Deviation 1890

PRIMARY outcome

Timeframe: Over 48 hours post-dose

Population: 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.

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.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Icatibant and Metabolites Icatibant	2320 ng*hr/mL Standard Deviation 402
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Icatibant and Metabolites Metabolite 1	1740 ng*hr/mL Standard Deviation 307
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Icatibant and Metabolites Metabolite 2	1950 ng*hr/mL Standard Deviation 345

SECONDARY outcome

Timeframe: TEAEs were collected after the single dose of icatibant until follow up, 5-7 days after icatibant administration

Population: The Safety Set consisted of all subjects who had taken the single dose of icatibant.

Treatment-emergent adverse events (TEAEs) were those that started after the single dose of icatibant.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
The Total Number of Treatment-Emergent Adverse Events	2 Treatment Emergent Adverse Events

SECONDARY outcome

Timeframe: Over 48 hours post-dose

Population: The Safety Set consisted of all subjects who had taken the single dose of icatibant.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
The Percentage of Subjects With Any Injection Site Reactions. Erythema	100.00 percentage of participants
The Percentage of Subjects With Any Injection Site Reactions. Warm sensation	50.00 percentage of participants
The Percentage of Subjects With Any Injection Site Reactions. Swelling	91.67 percentage of participants
The Percentage of Subjects With Any Injection Site Reactions. Cutaneous pain	33.33 percentage of participants
The Percentage of Subjects With Any Injection Site Reactions. Itching/Pruritus	8.33 percentage of participants
The Percentage of Subjects With Any Injection Site Reactions. Burning sensation	8.33 percentage of participants

SECONDARY outcome

Timeframe: Over 48 hours post-dose

Population: The Safety Set consisted of all subjects who had taken the single dose of icatibant.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results Screening	91.67 percentage of participants
Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results Day 1, Pre-dose	50.00 percentage of participants
Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results Baseline	50.00 percentage of participants
Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results Day 1, 0.75 hours	33.33 percentage of participants
Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results Day 1, 8 hours	33.33 percentage of participants
Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results Day 2, 24 hours	66.67 percentage of participants
Safety Evaluation Measured by Percentage of Subjects With Not Clinically Significant Abnormalities in ECG Results Day 3, 48 hours	66.67 percentage of participants

SECONDARY outcome

Timeframe: Over 48 hours post-dose

Population: The Safety Set consisted of all subjects who had taken the single dose of icatibant.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Change From Baseline in Diastolic Blood Pressure Day 1, 0.5 h	-2.0 mmHg Standard Deviation 6.42
Change From Baseline in Diastolic Blood Pressure Day 1, 1 h	-3.8 mmHg Standard Deviation 4.30
Change From Baseline in Diastolic Blood Pressure Day 1, 2 h	-5.2 mmHg Standard Deviation 4.57
Change From Baseline in Diastolic Blood Pressure Day 1, 6 h	-4.8 mmHg Standard Deviation 8.07
Change From Baseline in Diastolic Blood Pressure Day 1, 8 h	-4.5 mmHg Standard Deviation 6.67
Change From Baseline in Diastolic Blood Pressure Day 1, 12 h	-3.4 mmHg Standard Deviation 9.06
Change From Baseline in Diastolic Blood Pressure Day 2, 24 h	-1.8 mmHg Standard Deviation 7.76
Change From Baseline in Diastolic Blood Pressure Day 3, 48 h	-5.3 mmHg Standard Deviation 6.18
Change From Baseline in Diastolic Blood Pressure Day 1, 4 h	-5.2 mmHg Standard Deviation 7.52

SECONDARY outcome

Timeframe: Over 48 hours post-dose

Population: The Safety Set consisted of all subjects who had taken the single dose of icatibant.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Change From Baseline in Systolic Blood Pressure Day 1, 0.5 h	-1.8 mmHg Standard Deviation 12.07
Change From Baseline in Systolic Blood Pressure Day 1, 1 h	-1.9 mmHg Standard Deviation 13.03
Change From Baseline in Systolic Blood Pressure Day 1, 2 h	-5.8 mmHg Standard Deviation 14.21
Change From Baseline in Systolic Blood Pressure Day 1, 4 h	-7.3 mmHg Standard Deviation 17.06
Change From Baseline in Systolic Blood Pressure Day 1, 6 h	-4.3 mmHg Standard Deviation 16.20
Change From Baseline in Systolic Blood Pressure Day 1, 8 h	-3.0 mmHg Standard Deviation 11.52
Change From Baseline in Systolic Blood Pressure Day 1, 12 h	-4.4 mmHg Standard Deviation 14.11
Change From Baseline in Systolic Blood Pressure Day 2, 24 h	-6.2 mmHg Standard Deviation 11.98
Change From Baseline in Systolic Blood Pressure Day 3, 48 h	-6.4 mmHg Standard Deviation 12.72

SECONDARY outcome

Timeframe: Over 48 hours post-dose

Population: The Safety Set consisted of all subjects who had taken the single dose of icatibant.

Outcome measures

Measure	Icatibant (30 mg) n=12 Participants Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Change From Baseline in Pulse Rate Day 1, 0.5 h	1.4 beats per minute Standard Deviation 7.53
Change From Baseline in Pulse Rate Day 1, 1 h	0.1 beats per minute Standard Deviation 5.38
Change From Baseline in Pulse Rate Day 1, 2 h	-3.0 beats per minute Standard Deviation 9.67
Change From Baseline in Pulse Rate Day 1, 4 h	-6.3 beats per minute Standard Deviation 9.91
Change From Baseline in Pulse Rate Day 1, 6 h	-0.1 beats per minute Standard Deviation 11.15
Change From Baseline in Pulse Rate Day 1, 8 h	-3.6 beats per minute Standard Deviation 10.88
Change From Baseline in Pulse Rate Day 1, 12 h	-3.2 beats per minute Standard Deviation 10.50
Change From Baseline in Pulse Rate Day 2, 24 h	-6.8 beats per minute Standard Deviation 9.02
Change From Baseline in Pulse Rate Day 3, 48 h	-4.0 beats per minute Standard Deviation 9.77

Adverse Events

Icatibant (30 mg)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Icatibant (30 mg) n=12 participants at risk Subjects received a 30mg dose of icatibant administered as a single subcutaneous injection in the abdominal area on Day 1.
Musculoskeletal and connective tissue disorders Costochondritis	8.3% 1/12 • Number of events 1
General disorders Injection Site Pain	8.3% 1/12 • Number of events 1

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
• Publication restrictions are in place

Restriction type: OTHER