- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00242385
Pharmacokinetic Study of ARALAST (Human Alpha1- PI)
April 17, 2021 updated by: Baxalta now part of Shire
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
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.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
25
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
South Australia
-
Adelaide, South Australia, Australia
-
Woodville, South Australia, Australia
-
-
Victoria
-
Fitzroy, Victoria, Australia
-
-
Western Australia
-
Nedlands, Western Australia, Australia
-
-
-
-
-
Christchurch, New Zealand
-
Hamilton, New Zealand
-
-
Auckland
-
Otahuhu, Auckland, New Zealand
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ARALAST Fr. IV-1
60 mg/kg
|
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
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
|
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)
|
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
|
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
|
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
|
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
|
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
|
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.
|
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
|
Maximum Plasma Concentration (Cmax)
Time Frame: Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
|
Maximum α1-PI concentration following infusion
|
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-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.
|
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
|
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).
|
Pharmacokinetic evaluation: 30 minutes pre-infusion up to 35 days post-infusion
|
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
|
Throughout study period (7 months)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 20, 2005
Primary Completion (Actual)
June 5, 2006
Study Completion (Actual)
June 5, 2006
Study Registration Dates
First Submitted
October 19, 2005
First Submitted That Met QC Criteria
October 19, 2005
First Posted (Estimate)
October 20, 2005
Study Record Updates
Last Update Posted (Actual)
May 13, 2021
Last Update Submitted That Met QC Criteria
April 17, 2021
Last Verified
April 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Respiratory Tract Diseases
- Lung Diseases
- Liver Diseases
- Genetic Diseases, Inborn
- Subcutaneous Emphysema
- Emphysema
- Alpha 1-Antitrypsin Deficiency
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Serine Proteinase Inhibitors
- Trypsin Inhibitors
- Protease Inhibitors
- Alpha 1-Antitrypsin
Other Study ID Numbers
- 460501
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Alpha 1-Antitrypsin Deficiency
-
Thomayer University HospitalMasaryk UniversityRecruiting
-
University of FloridaAlpha-1 FoundationEnrolling by invitation
-
Grifols Therapeutics LLCCompletedAlpha₁-Antitrypsin DeficiencyUnited States
-
Michael Campos, MDCSL BehringCompletedAlpha 1 Antitrypsin DeficiencyUnited States
-
Washington University School of MedicineNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); N... and other collaboratorsTerminatedLiver Cirrhosis | Alpha-1-antitrypsin DeficiencyUnited States
-
Alnylam PharmaceuticalsTerminatedZZ Type Alpha-1 Antitrypsin Deficiency Liver DiseaseUnited Kingdom
-
University of PittsburghNational Heart, Lung, and Blood Institute (NHLBI)CompletedAlpha 1 Antitrypsin Deficiency | AATDUnited States
-
Hospices Civils de LyonCompletedChildren With a Deficiency of Alpha-1 AntitrypsinFrance
-
Heidelberg UniversityTerminatedHereditary Emphysema (Alpha 1-antitrypsin Deficiency)Germany
-
Grifols Therapeutics LLCCompletedEmphysema | Alpha 1-antitrypsin Deficiency (AATD)United States
Clinical Trials on Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase Inhibitor
-
Baxalta now part of ShireBaxalta Innovations GmbH, now part of ShireTerminatedChronic Obstructive Pulmonary Disease | Alpha1-antitrypsin DeficiencyUnited States, Canada, Australia
-
Grifols Therapeutics LLCCompletedEmphysema | Alpha 1-antitrypsin Deficiency (AATD)United States
-
Grifols Therapeutics LLCTerminatedType 1 Diabetes MellitusUnited States
-
Healthgen Biotechnology Corp.RecruitingEmphysema Secondary to Congenital AATDUnited States
-
Rockefeller UniversityBrigham and Women's Hospital; Weill Medical College of Cornell University; University...CompletedHealthy | HIVUnited States, Germany
-
Grifols Therapeutics LLCCompleted
-
Rockefeller UniversityUniversity of CologneCompletedHealthy | HIVGermany, United States
-
AM-PharmaCompleted
-
Grifols Therapeutics LLCTerminatedCOVID-19United States, Brazil, Chile, Colombia, Mexico
-
Bristol-Myers SquibbCompletedMelanomaFrance, Canada, United States, Germany, Australia, Russian Federation, Spain, Italy, Netherlands, Poland, Denmark, Israel, United Kingdom