Trial Outcomes & Findings for Pharmacokinetic Study of ARALAST (Human Alpha1- PI) (NCT NCT00242385)

NCT ID: NCT00242385

Last Updated: 2021-05-13

Results Overview

Area under the plasma alpha1-proteinase inhibitor (α1-PI) concentration versus time curve (AUC) calculated by linear trapezoidal method per dose.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 25 participants
• Primary outcome timeframe: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
• Results posted on: 2021-05-13

Participant Flow

Enrollment was conducted at seven clinical sites in Australia (4 sites) and New Zealand (3 sites) beginning in December 2005.

All 25 enrolled subjects were assigned to groups.

Participant milestones

Measure	ARALAST Fr. IV-1 Then Aralast Subjects were randomized to receive either single dose ARALAST 60 mg/kg or single-dose ARALAST Fr. IV-1 60 mg/kg at 0.2 mL/kg/min during the first treatment period with crossover to the alternate study product during the second treatment period, with a minimum of 7 days between the two treatment periods.	ARALAST Then ARALAST Fr. IV-1 Subjects were randomized to receive either single dose ARALAST 60 mg/kg or single-dose ARALAST Fr. IV-1 60 mg/kg at 0.2 mL/kg/min during the first treatment period with crossover to the alternate study product during the second treatment period, with a minimum of 7 days between the two treatment periods.
Period 1 STARTED	14	11
Period 1 COMPLETED	14	11
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	14	11
Period 2 COMPLETED	14	11
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetic Study of ARALAST (Human Alpha1- PI)

Baseline characteristics by cohort

Measure	Subjects With Severe Congenital α1-PI Deficiency n=25 Participants Subjects were randomized to receive either single dose ARALAST 60 mg/kg or single-dose ARALAST Fr. IV-1 60 mg/kg at 0.2 mL/kg/min during the first treatment period with crossover to the alternate study product during the second treatment period, with a minimum of 7 days between the two treatment periods.
Age, Continuous	59 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Region of Enrollment Australia	14 Participants n=5 Participants
Region of Enrollment New Zealand	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion

Population: All study subjects who received at least 1 dose of study product, and provided data suitable for pharmacokinetic analysis

Area under the plasma alpha1-proteinase inhibitor (α1-PI) concentration versus time curve (AUC) calculated by linear trapezoidal method per dose.

Outcome measures

Measure	ARALAST Fr. IV-1 n=25 Participants Single-dose ARALAST Fr. IV-1 60 mg/kg administered at 0.2 mL/kg/min	ARALAST n=25 Participants Single dose ARALAST 60 mg/kg administered at 0.2 mL/kg/min
Area Under the Curve/Dose	0.0822 days*kg/mL Interval 0.075 to 0.094	0.0920 days*kg/mL Interval 0.0804 to 0.098

SECONDARY outcome

Timeframe: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion

Population: Full Analysis Data Set - all study subjects who received at least 1 dose of study product, and provided data suitable for pharmacokinetic analysis

Total area under the α1-PI concentration vs. time curve from pharmacokinetic day 0 to time infinity (AUC 0-infinity) per dose

Outcome measures

Measure	ARALAST Fr. IV-1 n=25 Participants Single-dose ARALAST Fr. IV-1 60 mg/kg administered at 0.2 mL/kg/min	ARALAST n=25 Participants Single dose ARALAST 60 mg/kg administered at 0.2 mL/kg/min
Total Area Under the Curve Per Dose	0.0825 days*kg/mL Interval 0.075 to 0.095	0.0928 days*kg/mL Interval 0.0812 to 0.099

SECONDARY outcome

Timeframe: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion

Population: Full Analysis Data Set - all study subjects who received at least 1 dose of study product, and provided data suitable for pharmacokinetic analysis

Computed as dose divided by AUC 0-infinity (AUC 0-infinity was calculated as the sum of AUC from time 0 to the time of last quantifiable concentration plus a tail area correction)

Outcome measures

Measure	ARALAST Fr. IV-1 n=25 Participants Single-dose ARALAST Fr. IV-1 60 mg/kg administered at 0.2 mL/kg/min	ARALAST n=25 Participants Single dose ARALAST 60 mg/kg administered at 0.2 mL/kg/min
Systemic Clearance (CL)	951 mL/day Interval 782.0 to 1115.0	856 mL/day Interval 782.0 to 918.0

SECONDARY outcome

Timeframe: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion

Population: Full Analysis Data Set - all study subjects who received at least 1 dose of study product, and provided data suitable for pharmacokinetic analysis

Computed as total area under the moment curve (AUMC) divided by total AUC

Outcome measures

Measure	ARALAST Fr. IV-1 n=25 Participants Single-dose ARALAST Fr. IV-1 60 mg/kg administered at 0.2 mL/kg/min	ARALAST n=25 Participants Single dose ARALAST 60 mg/kg administered at 0.2 mL/kg/min
Mean Residence Time (MRT)	6.8 days Standard Deviation 3.9 • Interval 4.5 to 7.8	6.9 days Standard Deviation 2.8 • Interval 5.8 to 7.5

SECONDARY outcome

Timeframe: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion

Population: Full Analysis Data Set - all study subjects who received at least 1 dose of study product, and provided data suitable for pharmacokinetic analysis

Computed as weight-adjusted CL * MRT

Outcome measures

Measure	ARALAST Fr. IV-1 n=25 Participants Single-dose ARALAST Fr. IV-1 60 mg/kg administered at 0.2 mL/kg/min	ARALAST n=25 Participants Single dose ARALAST 60 mg/kg administered at 0.2 mL/kg/min
Apparent Volume of Distribution at Steady State	5606 mL Interval 4624.0 to 6162.0	5405 mL Interval 4454.0 to 6703.0

SECONDARY outcome

Timeframe: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion

Population: Full Analysis Data Set - all study subjects who received at least 1 dose of study product, and provided data suitable for pharmacokinetic analysis

Computed from the terminal or disposition rate constant obtained from log_e -linear fitting using the least squares deviation to the last five quantifiable concentrations above pre-infusion level.

Outcome measures

Measure	ARALAST Fr. IV-1 n=25 Participants Single-dose ARALAST Fr. IV-1 60 mg/kg administered at 0.2 mL/kg/min	ARALAST n=25 Participants Single dose ARALAST 60 mg/kg administered at 0.2 mL/kg/min
Terminal Half-life	4.1 days Interval 3.1 to 5.4	4.2 days Interval 4.0 to 5.2

SECONDARY outcome

Timeframe: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion

Population: Full Analysis Data Set - all study subjects who received at least 1 dose of study product, and provided data suitable for pharmacokinetic analysis

Maximum α1-PI concentration following infusion

Outcome measures

Measure	ARALAST Fr. IV-1 n=25 Participants Single-dose ARALAST Fr. IV-1 60 mg/kg administered at 0.2 mL/kg/min	ARALAST n=25 Participants Single dose ARALAST 60 mg/kg administered at 0.2 mL/kg/min
Maximum Plasma Concentration (Cmax)	1.7 mg/mL Interval 1.4 to 1.8	1.7 mg/mL Interval 1.5 to 1.8

SECONDARY outcome

Timeframe: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion

Population: Full Analysis Data Set - all study subjects who received at least 1 dose of study product, and provided data suitable for pharmacokinetic analysis

Time to reach C-max. Tmax is the number of days from infusion to maximum concentration. Samples drawn at the end of infusion are considered to be time zero.

Outcome measures

Measure	ARALAST Fr. IV-1 n=25 Participants Single-dose ARALAST Fr. IV-1 60 mg/kg administered at 0.2 mL/kg/min	ARALAST n=25 Participants Single dose ARALAST 60 mg/kg administered at 0.2 mL/kg/min
Time to Maximum α1-PI Concentration Post-infusion (Tmax)	0.00 days Interval 0.0 to 0.0	0.00 days Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion

Population: Full Analysis Data Set - all study subjects who received at least 1 dose of study product, and provided data suitable for pharmacokinetic analysis

Computed from Cmax (mg/ml) divided by dose per kg body weight (mg/kg).

Outcome measures

Measure	ARALAST Fr. IV-1 n=25 Participants Single-dose ARALAST Fr. IV-1 60 mg/kg administered at 0.2 mL/kg/min	ARALAST n=25 Participants Single dose ARALAST 60 mg/kg administered at 0.2 mL/kg/min
Incremental Recovery	0.0259 (mg/mL) / (mg/kg) Interval 0.0234 to 0.028	0.0258 (mg/mL) / (mg/kg) Interval 0.0237 to 0.027

SECONDARY outcome

Timeframe: Throughout study period (7 months)

Population: Safety Analysis Data Set - all study subjects who had evidence of receiving at least one dose of study medication regardless of any protocol violation.

Investigators assessed severity of AEs (occurring during or after infusions) based on: MILD: Transient discomfort, does not interfere in a significant manner with participant's normal functioning level; Resolves spontaneously or may require minimal therapeutic intervention MODERATE: AE produces limited impairment of function, can require therapeutic intervention; AE produces no sequelae; SEVERE: AE results in marked impairment of function, can lead to temporary inability to resume usual life pattern; AE produces sequelae, which require prolonged therapeutic intervention

Outcome measures

Measure	ARALAST Fr. IV-1 n=25 Participants Single-dose ARALAST Fr. IV-1 60 mg/kg administered at 0.2 mL/kg/min	ARALAST n=25 Participants Single dose ARALAST 60 mg/kg administered at 0.2 mL/kg/min
Adverse Events (AEs) Serious AEs	0 Events	0 Events
Adverse Events (AEs) Non-Serious AEs - Mild	43 Events	45 Events
Adverse Events (AEs) Non-Serious AEs - Moderate	16 Events	12 Events
Adverse Events (AEs) Non-Serious AEs - Severe	2 Events	3 Events

Adverse Events

ARALAST Fr. IV-1

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

ARALAST

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	ARALAST Fr. IV-1 n=25 participants at risk Subjects received a single dose of ARALAST Fr. IV-1 60 mg/kg at 0.2 mL/kg/min	ARALAST n=25 participants at risk Subjects received a single dose of ARALAST 60 mg/kg at 0.2 mL/kg/min
Gastrointestinal disorders Nausea	8.0% 2/25 • Number of events 2 • Throughout the entire study period (7 months)	12.0% 3/25 • Number of events 3 • Throughout the entire study period (7 months)
General disorders Vessel puncture site bruise	12.0% 3/25 • Number of events 3 • Throughout the entire study period (7 months)	8.0% 2/25 • Number of events 6 • Throughout the entire study period (7 months)
Infections and infestations Nasopharyngitis	8.0% 2/25 • Number of events 2 • Throughout the entire study period (7 months)	4.0% 1/25 • Number of events 1 • Throughout the entire study period (7 months)
Infections and infestations Upper respiratory tract infection	12.0% 3/25 • Number of events 3 • Throughout the entire study period (7 months)	4.0% 1/25 • Number of events 1 • Throughout the entire study period (7 months)
Injury, poisoning and procedural complications Contusion	0.00% 0/25 • Throughout the entire study period (7 months)	12.0% 3/25 • Number of events 4 • Throughout the entire study period (7 months)
Musculoskeletal and connective tissue disorders Muscle strain	8.0% 2/25 • Number of events 2 • Throughout the entire study period (7 months)	4.0% 1/25 • Number of events 1 • Throughout the entire study period (7 months)
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	8.0% 2/25 • Number of events 4 • Throughout the entire study period (7 months)	8.0% 2/25 • Number of events 2 • Throughout the entire study period (7 months)
Musculoskeletal and connective tissue disorders Myalgia	4.0% 1/25 • Number of events 1 • Throughout the entire study period (7 months)	8.0% 2/25 • Number of events 2 • Throughout the entire study period (7 months)
Nervous system disorders Headache	16.0% 4/25 • Number of events 5 • Throughout the entire study period (7 months)	4.0% 1/25 • Number of events 3 • Throughout the entire study period (7 months)
Nervous system disorders Lethargy	4.0% 1/25 • Number of events 1 • Throughout the entire study period (7 months)	8.0% 2/25 • Number of events 2 • Throughout the entire study period (7 months)
Respiratory, thoracic and mediastinal disorders Cough	12.0% 3/25 • Number of events 3 • Throughout the entire study period (7 months)	4.0% 1/25 • Number of events 2 • Throughout the entire study period (7 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/25 • Throughout the entire study period (7 months)	8.0% 2/25 • Number of events 4 • Throughout the entire study period (7 months)
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	12.0% 3/25 • Number of events 3 • Throughout the entire study period (7 months)	8.0% 2/25 • Number of events 2 • Throughout the entire study period (7 months)
Skin and subcutaneous tissue disorders Blister	0.00% 0/25 • Throughout the entire study period (7 months)	8.0% 2/25 • Number of events 2 • Throughout the entire study period (7 months)

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee Baxter's agreements with PIs vary per individual PI, but contain common elements. Baxter requires a review of results communications (e.g., for confidential information) ≥60 days prior to submission or communication. Baxter may request an additional delay of up to 60 days (e.g., to allow for intellectual property protection).
• Publication restrictions are in place

Restriction type: OTHER