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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00242385




Registration number
NCT00242385
Ethics application status
Date submitted
19/10/2005
Date registered
20/10/2005
Date last updated
24/11/2017

Titles & IDs
Public title
Pharmacokinetic Study of ARALAST (Human Alpha1- PI)
Scientific title
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
Secondary ID [1] 0 0
460501
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alpha 1-Antitrypsin Deficiency 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor
Other interventions - Dose of 60 mg/kg alpha1-proteinase inhibitor

Experimental: ARALAST Fr. IV-1 - 60 mg/kg

Active Comparator: ARALAST - 60mg/kg


Other interventions: Dose 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.

Other interventions: Dose 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.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Curve/Dose - Area under the plasma alpha1-proteinase inhibitor (a1-PI) concentration versus time curve (AUC) calculated by linear trapezoidal method per dose.
Timepoint [1] 0 0
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary outcome [1] 0 0
Total Area Under the Curve Per Dose - Total area under the a1-PI concentration vs. time curve from pharmacokinetic day 0 to time infinity (AUC 0-infinity) per dose
Timepoint [1] 0 0
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary outcome [3] 0 0
Mean Residence Time (MRT) - Computed as total area under the moment curve (AUMC) divided by total AUC
Timepoint [3] 0 0
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary outcome [4] 0 0
Apparent Volume of Distribution at Steady State - Computed as weight-adjusted CL * MRT
Timepoint [4] 0 0
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary outcome [6] 0 0
Maximum Plasma Concentration (Cmax) - Maximum a1-PI concentration following infusion
Timepoint [6] 0 0
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary outcome [7] 0 0
Time to Maximum a1-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.
Timepoint [7] 0 0
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary outcome [8] 0 0
Incremental Recovery - Computed from Cmax (mg/ml) divided by dose per kg body weight (mg/kg).
Timepoint [8] 0 0
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Throughout study period (7 months)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Woodville
Recruitment hospital [3] 0 0
- Fitzroy
Recruitment hospital [4] 0 0
- Nedlands
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Woodville
Recruitment postcode(s) [3] 0 0
- Fitzroy
Recruitment postcode(s) [4] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch
Country [3] 0 0
New Zealand
State/province [3] 0 0
Hamilton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Baxalta now part of Shire
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Baxter Healthcare Corporation
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 (a1-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 website
https://clinicaltrials.gov/show/NCT00242385
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jeff Garrett, MD
Address 0 0
Middlemore Hospital, Otahuhu, Auckland, New Zealand
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications