A Pharmacokinetic Study of AA4500 (XIAFLEX™, Proposed Name) in Subjects With Dupuytren's Contracture
A Phase 1, open-label, single-dose pharmacokinetic study in subjects with Dupuytren's contracture conducted at one site in the United States. All subjects received a single dose of AA4500 0.58 mg, which was injected directly into the cord affecting either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint. Pharmacokinetic blood samples were collected before dosing, at predetermined time points through the 24 hours after dosing, Day 7, and Day 30. Efficacy and safety assessments were performed up to 30 days after the AA4500 0.58 injection.
This study was designed to be part of the larger clinical program, for adult patients with Dupuytren's contracture with a palpable cord, where the data from 2 pivotal Placebo-Controlled studies (AUX-CC-857 [NCT00528606]and AUX-CC-859 [NCT00533273]) and 7 non-pivotal studies were evaluated.
|Dupuytren's Contracture||Biological: collagenase clostridium histolyticum||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
|Official Title:||A Phase 1, Open-Label Study to Assess the Pharmacokinetics and Safety of a Single Injection of AA4500 0.58 mg in Subjects With Dupuytren's Contracture|
- Number of Subjects With AUX I and AUX II Detected in Their Blood After a Single Dose of AA4500 [ Time Frame: Before dosing, at predetermined time points through the 24 hours after dosing, Day 7, and Day 30 ]AUX I and AUX II are the constituent protein collagenases of collagenase clostridium histolyticum (AA4500). Plasma concentrations of AUX I and AUX II were assessed through an enzymye-linked-immunoabsorbent assay (ELISA).
- Clinical Success [ Time Frame: 30 days after treatment to the primary joint ]Clinical success defined as a reduction in contracture (ie, flexion deformity) to ≤5° of normal as measured by finger goniometry 30 days after an injection. Last observation carried forward (LOCF) after the injection was used if the status at day 30 could not be determined.
- Clinical Improvement [ Time Frame: 30 days after treatment to the primary joint ]Clinical improvement defined as ≥50% reduction from baseline in contracture within 30 days of the injection. LOCF after the injection was used if the status at day 30 could not be determined.
- Percent Change From Baseline Contracture [ Time Frame: Baseline, 30 days after treatment to the primary joint ]Change from baseline in the degree of fixed-flexion contracture calculated as 100 times (baseline contracture minus last available post-injection contracture measurement) divided by baseline contracture where a positive change indicates a reduction in the degree of contracture.
- Change From Baseline Range of Motion [ Time Frame: Baseline, 30 days after treatment to the primary joint ]Range of motion defined as the difference between the finger extension angle and finger flexion angle expressed in degrees
|Study Start Date:||September 2007|
|Study Completion Date:||March 2008|
|Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
|Experimental: AA4500 0.58 mg||
Biological: collagenase clostridium histolyticum
Single dose of AA4500 0.58 mg into the cord
Please refer to this study by its ClinicalTrials.gov identifier: NCT00528931
|United States, California|
|Providence Clinical Research|
|Burbank, California, United States, 91505|
|Study Director:||Veronica Urdaneta, MD||Endo Pharmaceuticals|