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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AA4500 0.58 mg | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| collagenase clostridium histolyticum | Biological | Single dose of AA4500 0.58 mg into the cord |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With AUX I and AUX II Detected in Their Blood After a Single Dose of AA4500 | 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). | Before dosing, at predetermined time points through the 24 hours after dosing, Day 7, and Day 30 |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Success | 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. | 30 days after treatment to the primary joint |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Veronica Urdaneta, MD | Endo USA Inc., a Keenova Therapeutics Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Providence Clinical Research | Burbank | California | 91505 | United States |
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| Label | URL |
|---|---|
| XIAFLEX Prescribing Information | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | AA4500 0.58 mg | collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | AA4500 0.58 mg | collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects With AUX I and AUX II Detected in Their Blood After a Single Dose of AA4500 | 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). | Pharmacokinetic population | Posted | Number | participants | Before dosing, at predetermined time points through the 24 hours after dosing, Day 7, and Day 30 |
|
From the time that the first dose of study drug was administered until 30 days elapsed following discontinuation of study drug administration.
This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide & XIAFLEX Prescribing Information (see links above).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AA4500 0.58 mg | collagenase clostridium histolyticum 0.58mg injected into either the metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tendon rupture | Injury, poisoning and procedural complications | MedDRA (8.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blister | Skin and subcutaneous tissue disorders | MedDRA (8.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Coordinator | Endo Pharmaceuticals, Inc. | clinicalsite.inquiries@endo.com |
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| ID | Term |
|---|---|
| D004387 | Dupuytren Contracture |
| ID | Term |
|---|---|
| D005350 | Fibroma |
| D018218 | Neoplasms, Fibrous Tissue |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
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| ID | Term |
|---|---|
| D003012 | Microbial Collagenase |
| ID | Term |
|---|---|
| D017364 | Collagenases |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
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| Clinical Improvement |
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. |
| 30 days after treatment to the primary joint |
| Percent Change From Baseline Contracture | 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. | Baseline, 30 days after treatment to the primary joint |
| Change From Baseline Range of Motion | Range of motion defined as the difference between the finger extension angle and finger flexion angle expressed in degrees | Baseline, 30 days after treatment to the primary joint |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | Clinical Success | 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. | Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection | Posted | Number | Percentage of joints | 30 days after treatment to the primary joint | Joints | Joints |
|
|
|
| Secondary | Clinical Improvement | 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. | Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection. | Posted | Number | Percentage of joints | 30 days after treatment to the primary joint | Joints | Joints |
|
|
|
| Secondary | Percent Change From Baseline Contracture | 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. | Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection. | Posted | Mean | Standard Deviation | Percentage of contracture change | Baseline, 30 days after treatment to the primary joint | Joints | Joints |
|
|
|
| Secondary | Change From Baseline Range of Motion | Range of motion defined as the difference between the finger extension angle and finger flexion angle expressed in degrees | Efficacy assessment based on safety population which included all enrolled subjects who received the AA4500 injection. | Posted | Mean | Standard Deviation | Degrees | Baseline, 30 days after treatment to the primary joint | Joints | Joints |
|
|
|
| 1 |
| 16 |
| 16 |
| 16 |
| Blood urine present | Investigations | MedDRA (8.0) | Non-systematic Assessment |
|
| Burning sensation | Nervous system disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (8.0) | Non-systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Injection site haemorrhage | General disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Injection site oedema | General disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Injection site swelling | General disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA (8.0) | Non-systematic Assessment |
|
Auxilium Pharmaceuticals, Inc. agreements may vary with individual investigators but will not prohibit any investigator from publishing. Auxilium supports the publication of results from all centers of a multicenter trial but requests that reports based on single site data not preceed the primary publication of the entire clinical trial.
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D003286 | Contracture |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006867 |
| Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |