We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pharmacokinetic Study of ARALAST (Human Alpha1- PI)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00242385
First Posted: October 20, 2005
Last Update Posted: July 21, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Baxter Healthcare Corporation
Information provided by:
Shire
  Purpose
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.

Condition Intervention Phase
Alpha 1-Antitrypsin Deficiency Biological: Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor Biological: Dose of 60 mg/kg alpha1-proteinase inhibitor Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Area Under the Curve/Dose [ Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion ]
    Area under the plasma alpha1-proteinase inhibitor (α1-PI) concentration versus time curve (AUC) calculated by linear trapezoidal method per dose.


Secondary Outcome Measures:
  • Total Area Under the Curve Per Dose [ Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion ]
    Total area under the α1-PI concentration vs. time curve from pharmacokinetic day 0 to time infinity (AUC 0-infinity) per dose

  • Systemic Clearance (CL) [ Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion ]
    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)

  • Mean Residence Time (MRT) [ Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion ]
    Computed as total area under the moment curve (AUMC) divided by total AUC

  • Apparent Volume of Distribution at Steady State [ Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion ]
    Computed as weight-adjusted CL * MRT

  • Terminal Half-life [ Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion ]
    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.

  • Maximum Plasma Concentration (Cmax) [ Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion ]
    Maximum α1-PI concentration following infusion

  • Time to Maximum α1-PI Concentration Post-infusion (Tmax) [ Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion ]
    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.

  • Incremental Recovery [ Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion ]
    Computed from Cmax (mg/ml) divided by dose per kg body weight (mg/kg).

  • Adverse Events (AEs) [ Time Frame: Throughout study period (7 months) ]

    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



Enrollment: 25
Study Start Date: December 2005
Study Completion Date: June 2006
Arms Assigned Interventions
Experimental: ARALAST Fr. IV-1
60 mg/kg
Biological: 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.
Active Comparator: ARALAST
60mg/kg
Biological: 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00242385


Locations
Australia, South Australia
Adelaide, South Australia, Australia
Woodville, South Australia, Australia
Australia, Victoria
Fitzroy, Victoria, Australia
Australia, Western Australia
Nedlands, Western Australia, Australia
New Zealand
Otahuhu, Auckland, New Zealand
Christchurch, New Zealand
Hamilton, New Zealand
Sponsors and Collaborators
Shire
Baxter Healthcare Corporation
Investigators
Principal Investigator: Jeff Garrett, MD Middlemore Hospital, Otahuhu, Auckland, New Zealand
  More Information

Responsible Party: David Gelmont, MD, Global Medical Director, Head of Specialty Products TA, BioTherapeutics, Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT00242385     History of Changes
Other Study ID Numbers: 460501
First Submitted: October 19, 2005
First Posted: October 20, 2005
Results First Submitted: February 15, 2011
Results First Posted: July 20, 2011
Last Update Posted: July 21, 2015
Last Verified: July 2011

Keywords provided by Shire:
Severe congenital Alpha1-Proteinase Inhibitor (Alpha1-PI) deficiency

Additional relevant MeSH terms:
Alpha 1-Antitrypsin Deficiency
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
Pathologic Processes
Protease Inhibitors
Alpha 1-Antitrypsin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypsin Inhibitors
Serine Proteinase Inhibitors