Pharmacokinetic Study of ARALAST (Human Alpha1- PI)
Single-Dose, Double-Blind, Crossover Study to Evaluate the Pharmacokinetic Comparability of ARALAST Fraction IV-1 Alpha1-Proteinase Inhibitor (ARALAST Fr. IV-1) and ARALAST
1 other identifier
interventional
25
2 countries
7
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Dec 2005
Shorter than P25 for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 19, 2005
CompletedFirst Posted
Study publicly available on registry
October 20, 2005
CompletedStudy Start
First participant enrolled
December 20, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 5, 2006
CompletedStudy Completion
Last participant's last visit for all outcomes
June 5, 2006
CompletedResults Posted
Study results publicly available
July 20, 2011
CompletedMay 13, 2021
April 1, 2021
6 months
October 19, 2005
February 15, 2011
April 17, 2021
Conditions
Keywords
Outcome Measures
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.
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary Outcomes (9)
Total Area Under the Curve Per Dose
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Systemic Clearance (CL)
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Mean Residence Time (MRT)
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Apparent Volume of Distribution at Steady State
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Terminal Half-life
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
- +4 more secondary outcomes
Study Arms (2)
ARALAST Fr. IV-1
EXPERIMENTAL60 mg/kg
ARALAST
ACTIVE COMPARATOR60mg/kg
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Unknown Facility
Adelaide, South Australia, Australia
Unknown Facility
Woodville, South Australia, Australia
Unknown Facility
Fitzroy, Victoria, Australia
Unknown Facility
Nedlands, Western Australia, Australia
Unknown Facility
Otahuhu, Auckland, New Zealand
Unknown Facility
Christchurch, New Zealand
Unknown Facility
Hamilton, New Zealand
Related Publications (1)
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.
PMID: 36001294DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Shire
Study Officials
- STUDY DIRECTOR
Study Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 19, 2005
First Posted
October 20, 2005
Study Start
December 20, 2005
Primary Completion
June 5, 2006
Study Completion
June 5, 2006
Last Updated
May 13, 2021
Results First Posted
July 20, 2011
Record last verified: 2021-04