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CompletedNCT00242385Updated May 13, 2021Results posted

Pharmacokinetic Study of ARALAST (Human Alpha1- PI)

A Phase 1 interventional study of Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor and Dose of 60 mg/kg alpha1-proteinase inhibitor in Alpha 1-Antitrypsin Deficiency, sponsored by Baxalta now part of Shire. Completed at 7 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-05-13.

Sponsored by Baxalta now part of Shire · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
25
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The primary purpose of this study is to characterize the pharmacokinetic profile of intravenous Aralast Fraction (Fr.) IV-1, a sterile, stable, lyophilized preparation of functionally intact human Alpha1- Proteinase Inhibitor (α1-PI). This pharmacokinetic study will be a randomized controlled clinical trial with a cross-over design. Twenty-four subjects will be enrolled into the study. Overall study duration will be approximately 6-8 months.

02

Conditions studied

  • Alpha 1-Antitrypsin Deficiency

Keywords

  • Severe congenital Alpha1-Proteinase Inhibitor (Alpha1-PI) deficiency
03

In context

Alpha 1-Antitrypsin Deficiency

94 studies on the registry are indexed under Alpha 1-Antitrypsin Deficiency; 5 are open to participants now.

This study's enrollment of 25 is close to the median of 27 across 58 interventional studies indexed under Alpha 1-Antitrypsin Deficiency.

Browse Alpha 1-Antitrypsin Deficiency studies →

Lead sponsor

Baxalta now part of Shire is the lead sponsor of 110 studies on the registry; none are open to participants now.

Of its 18 completed or terminated interventional studies of FDA-regulated products, 16 (89%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • The subject or subject´s legally authorized representative has provided written informed consent
  • Subject is 18 years of age or older
  • Subject has a documented, endogenous plasma Alpha1-PI level \< 8 Micromolar
  • Subject is of the genotype Pi*Z/Z, Pi*Z/Null, Pi*Null/Null, Pi*Malton/Z, or others, dependent on the approval by the Sponsor
  • If the subject is female or of childbearing potential, the subject has a negative urine test for pregnancy within 7 days prior to first study product administration and agrees to employ adequate birth control measures for the duration of the study

  • Laboratory results obtained at the screening visit, meeting the following criteria:

    • Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) \<= 2 times the upper limit of normal (ULN)
    • Serum total bilirubin \<= 2 times ULN
    • Proteinuria \< +2 on dipstick analysis
    • Serum creatinine \<= 1.5 times ULN
    • Absolute neutrophil count (ANC) >= 1500 cells/mm3
    • Hemoglobin >= 10.0 g/dL
    • Platelet count >= 10\^5/mm3
  • If the subject is treated with any respiratory medications, including inhaled bronchodilators and inhaled or oral corticosteroids, the subjects´ medication doses were unchanged for at least 14 days prior to first study product administration
  • Nonsmoker for a minimum of 3 months prior to first study product administration

Exclusion criteria

Exclusion Criteria:

  • The subject has received any Alpha1-PI augmentation therapy (including Aralast and investigational Alpha1-PIs, by any route including intravenous and inhaled) within 42 days prior to first study product administration
  • The subject has received an investigational drug or device within 1 month prior to first study product administration, or the subject is currently receiving an investigational drug
  • The subject has a known selective immunoglobulin A (IgA) deficiency (IgA level \< 15 mg/dL) and/or antibody to IgA
  • The subject has a pulmonary exacerbation or had a pulmonary exacerbation in the past 14 days prior to first study product administration
  • The subject is pregnant or lactating, or intends to become pregnant during the course of the study
  • The subject has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double
Enrollment
25 participants (actual)

Study arms

  • Experimental
    ARALAST Fr. IV-1

    60 mg/kg

    Biological: Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor

  • Active comparator
    ARALAST

    60mg/kg

    Biological: Dose of 60 mg/kg alpha1-proteinase inhibitor

Interventions

  • BiologicalDose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor

    Subjects meeting the eligibility criteria were randomized to receive either single dose ARALAST alpha1-proteinase inhibitor 60 mg/kg or single-dose ARALAST alpha1-proteinase inhibitor 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.

  • BiologicalDose of 60 mg/kg alpha1-proteinase inhibitor

    Subjects meeting the eligibility criteria were randomized to receive either single dose ARALAST alpha1-proteinase inhibitor 60 mg/kg or single-dose ARALAST alpha1-proteinase inhibitor 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.

06

What researchers measure

Primary outcomes

  1. Area Under the Curve/Dose

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

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

Secondary outcomes

  1. Total Area Under the Curve Per Dose

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

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

  2. Systemic Clearance (CL)

    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)

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

  3. Mean Residence Time (MRT)

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

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

  4. Apparent Volume of Distribution at Steady State

    Computed as weight-adjusted CL \* MRT

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

  5. Terminal Half-life

    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.

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

  6. Maximum Plasma Concentration (Cmax)

    Maximum α1-PI concentration following infusion

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

  7. Time to Maximum α1-PI Concentration Post-infusion (Tmax)

    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.

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

  8. Incremental Recovery

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

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

  9. Adverse Events (AEs)

    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

    Time frame: Throughout study period (7 months)

07

Results

Posted Jul 20, 2011

Participant flow

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

Period 1
Participant flow — Period 1
MilestoneARALAST Fr. IV-1 Then AralastARALAST Then ARALAST Fr. IV-1
Started1411
Completed1411
Not completed00
Period 2
Participant flow — Period 2
MilestoneARALAST Fr. IV-1 Then AralastARALAST Then ARALAST Fr. IV-1
Started1411
Completed1411
Not completed00

Outcome measures

PrimaryArea Under the Curve/Dose

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

Time frame:
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Reported as:
Median · days*kg/mL
Area Under the Curve/Dose
days*kg/mLARALAST Fr. IV-1ARALAST
Area Under the Curve/Dose0.0822 (0.0750 to 0.094)0.0920 (0.0804 to 0.098)
Statistical analysis
  • ARALAST Fr. IV-1 vs ARALAST · Ratio of geometric means: 0.928 · 90% CI 0.858 to 1.002
SecondaryTotal Area Under the Curve Per Dose

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

Time frame:
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Reported as:
Median · days*kg/mL
Total Area Under the Curve Per Dose
days*kg/mLARALAST Fr. IV-1ARALAST
Total Area Under the Curve Per Dose0.0825 (0.0750 to 0.095)0.0928 (0.0812 to 0.099)
Statistical analysis
  • ARALAST Fr. IV-1 vs ARALAST · Ratio of geometric means: 0.934 · 90% CI 0.855 to 1.021
SecondarySystemic Clearance (CL)

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)

Time frame:
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Reported as:
Median · mL/day
Systemic Clearance (CL)
mL/dayARALAST Fr. IV-1ARALAST
Systemic Clearance (CL)951 (782 to 1115)856 (782 to 918)
SecondaryMean Residence Time (MRT)

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

Time frame:
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Reported as:
Mean · days
Mean Residence Time (MRT)
daysARALAST Fr. IV-1ARALAST
Mean Residence Time (MRT)6.8 ± 3.96.9 ± 2.8
SecondaryApparent Volume of Distribution at Steady State

Computed as weight-adjusted CL \* MRT

Time frame:
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Reported as:
Median · mL
Apparent Volume of Distribution at Steady State
mLARALAST Fr. IV-1ARALAST
Apparent Volume of Distribution at Steady State5606 (4624 to 6162)5405 (4454 to 6703)
SecondaryTerminal Half-life

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.

Time frame:
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Reported as:
Median · days
Terminal Half-life
daysARALAST Fr. IV-1ARALAST
Terminal Half-life4.1 (3.1 to 5.4)4.2 (4.0 to 5.2)
SecondaryMaximum Plasma Concentration (Cmax)

Maximum α1-PI concentration following infusion

Time frame:
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Reported as:
Median · mg/mL
Maximum Plasma Concentration (Cmax)
mg/mLARALAST Fr. IV-1ARALAST
Maximum Plasma Concentration (Cmax)1.7 (1.4 to 1.8)1.7 (1.5 to 1.8)
SecondaryTime to Maximum α1-PI Concentration Post-infusion (Tmax)

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.

Time frame:
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Reported as:
Median · days
Time to Maximum α1-PI Concentration Post-infusion (Tmax)
daysARALAST Fr. IV-1ARALAST
Time to Maximum α1-PI Concentration Post-infusion (Tmax)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)
SecondaryIncremental Recovery

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

Time frame:
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Reported as:
Median · (mg/mL) / (mg/kg)
Incremental Recovery
(mg/mL) / (mg/kg)ARALAST Fr. IV-1ARALAST
Incremental Recovery0.0259 (0.0234 to 0.028)0.0258 (0.0237 to 0.027)
SecondaryAdverse Events (AEs)

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

Time frame:
Throughout study period (7 months)
Reported as:
Number · Events
Adverse Events (AEs)
EventsARALAST Fr. IV-1ARALAST
Serious AEs00
Non-Serious AEs - Mild4345
Non-Serious AEs - Moderate1612
Non-Serious AEs - Severe23

Adverse events

Collected over Throughout the entire study period (7 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
ARALAST Fr. IV-1—0/25 (0%)23/25 (92%)
ARALAST—0/25 (0%)19/25 (76%)
Most frequent other events
Showing 10 of 14
Most frequent other events
EventARALAST Fr. IV-1ARALAST
HeadacheNervous system disorders4/251/25
NauseaGastrointestinal disorders2/253/25
Vessel puncture site bruiseGeneral disorders3/252/25
Upper respiratory tract infectionInfections and infestations3/251/25
ContusionInjury, poisoning and procedural complications0/253/25
CoughRespiratory, thoracic and mediastinal disorders3/251/25
Pharyngolaryngeal painRespiratory, thoracic and mediastinal disorders3/252/25
NasopharyngitisInfections and infestations2/251/25
Muscle strainMusculoskeletal and connective tissue disorders2/251/25
Musculoskeletal discomfortMusculoskeletal and connective tissue disorders2/252/25

Baseline characteristics

Age, Continuous
Age, Continuous(years)Subjects With Severe Congenital α1-PI Deficiency
Median59 (20 to 75)
Sex: Female, Male
Sex: Female, Male(Participants)Subjects With Severe Congenital α1-PI Deficiency
Female8
Male17
Region of Enrollment
Region of Enrollment(Participants)Subjects With Severe Congenital α1-PI Deficiency
Australia14
New Zealand11
08

Study locations

7 sites
  • Adelaide, South Australia, Australia
  • Woodville, South Australia, Australia
  • Fitzroy, Victoria, Australia
  • Nedlands, Western Australia, Australia
  • Otahuhu, Auckland, New Zealand
  • Christchurch, New Zealand
  • Hamilton, New Zealand
09

References and documents

Publications

  • Li Z, Franke RM, Morris DN, Yel L. Pharmacokinetics and Biochemical Efficacy of an alpha1-Proteinase Inhibitor (Aralast NP) in alpha1-Antitrypsin Deficiency: a Cross-Product Retrospective Comparability Analysis. Pulm Ther. 2022 Sep;8(3):311-326. doi: 10.1007/s41030-022-00199-4. Epub 2022 Aug 24. PubMed 36001294 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 13, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00242385
Lead sponsor
Baxalta now part of Shire
Collaborators
Baxter Healthcare, Ltd. (New Zealand), Baxter Healthcare Pty. Ltd. (Australia)
Responsible party
Sponsor
First posted
Oct 20, 2005
Start date
Dec 20, 2005
Primary completion
Jun 5, 2006
Completion
Jun 5, 2006
Results posted
Jul 20, 2011
Last update
May 13, 2021

Study contacts

Study Director
study director · Takeda
View the source record on ClinicalTrials.gov ↗

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