A Pharmacokinetic Study of AA4500 (XIAFLEX™, Proposed Name) in Subjects With Dupuytren's Contracture - Full Text View

Purpose

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.

Condition	Intervention	Phase
Dupuytren's Contracture	Biological: collagenase clostridium histolyticum	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Drug Information available for: Collagenase

U.S. FDA Resources

Further study details as provided by Auxilium Pharmaceuticals:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical Success [ Time Frame: 30 days after treatment to the primary joint ] [ Designated as safety issue: No ]
A clinical success is defined as a reduction in contracture (ie, flexion deformity) to ≤ 5° of normal as measured by finger goniometry 30 days after an injection. If the Day 30 visit is missing, the last observation carried forward (LOCF) completed after the injection (Day 1 or Day 7) will be used to determine clinical success
Clinical Improvement [ Time Frame: 30 days after first treatment to the primary joint ] [ Designated as safety issue: No ]
A clinical improvement is defined as a ≥ 50% reduction from baseline in contracture after an injection
Percent Reduction From Baseline Contracture [ Time Frame: 30 days after first treatment to the primary joint ] [ Designated as safety issue: No ]
Change From Baseline Range of Motion [ Time Frame: 30 days after first treatment to the primary joint ] [ Designated as safety issue: No ]
Difference between the finger extension angle and finger flexion angle expressed in degrees
Time to First Achieve and Maintain Clinical Success [ Time Frame: First evaluation visit on which clinical success is achieved and maintained through the Day 30 evaluation of the primary joint ] [ Designated as safety issue: No ]
Time to clinical success is defined as the number of days after the first injection in the joint to reach clinical success

Enrollment:	16
Study Start Date:	September 2007
Study Completion Date:	March 2008
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: AA4500 0.58 mg	Biological: collagenase clostridium histolyticum Single dose of AA4500 0.58 mg into the cord Other Names: XIAFLEX® AA4500

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects with a diagnosis of Dupuytren's contracture, with a fixed flexion deformity of at least one finger, other than the thumb, that had a contracture at least 20°, but not greater than 100° for MP (80° for PIP) joints, caused by a palpable cord.
Had a positive "table top test," defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top.
Were naive to AA4500 treatment.
Were judged to be in good health.

Exclusion Criteria:

Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands.
Had received treatment for Dupuytren's contracture within 90 days of the AA4500 injection to the MP or PIP selected, including surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon on the selected primary joint within 90 days before the first dose of study drug.
Had a known recent history of stroke, bleeding, a disease process that affected the hands, or other medical condition, which in the investigator's opinion, would make the subject unsuitable for enrollment in the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00528931

Locations

United States, California
Providence Clinical Research
Burbank, California, United States, 91505

Sponsors and Collaborators

Auxilium Pharmaceuticals

Investigators

Study Director:

John Rodzvilla, MD

Auxilium Pharmaceuticals, Inc

More Information

Additional Information:

XIAFLEX Medication Guide This link exits the ClinicalTrials.gov site

XIAFLEX Prescribing Information This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Auxilium Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00528931 History of Changes
Other Study ID Numbers:	AUX-CC-855
Study First Received:	September 11, 2007
Results First Received:	September 24, 2010
Last Updated:	July 11, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Auxilium Pharmaceuticals:

Assessment of AUX I and/or AUX II in human plasma

Additional relevant MeSH terms:

Contracture
Dupuytren Contracture
Joint Diseases

Musculoskeletal Diseases
Muscular Diseases
Connective Tissue Diseases

ClinicalTrials.gov processed this record on May 16, 2013