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Clinical Study for the Treatment of Adhesive Capsulitis of the Shoulder (AC)

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ClinicalTrials.gov Identifier: NCT02006719
Recruitment Status : Completed
First Posted : December 10, 2013
Results First Posted : May 25, 2017
Last Update Posted : October 5, 2017
Sponsor:
Information provided by (Responsible Party):
Endo Pharmaceuticals

Brief Summary:
The objectives of this study are to assess the safety, effectiveness, and immunogenicity of AA4500 in the treatment of adhesive capsulitis.

Condition or disease Intervention/treatment Phase
Adhesive Capsulitis Frozen Shoulder Biological: Collagenase Clostridium Histolyticum Other: Placebo Phase 2

Detailed Description:

Study is a Phase 2b, double-blind, placebo-controlled study of the safety and efficacy of AA4500 for the treatment of adhesive capsulitis of the shoulder. To be eligible for treatment, a subject must have unilateral idiopathic adhesive capsulitis of the shoulder with restricted range of motion in the affected shoulder for at least 3 months but not more than 12 months. Subjects will be screened for study eligibility within 28 days before injection of study drug.

Approximately 300 adult women and men are to be enrolled in this study. Following screening and determination of study eligibility, subjects will be randomized 3:1 to receive 0.58 mg of AA4500 or placebo. Subjects will receive up to 3 injections of study drug. Each injection will be separated by a minimum of 21 days. Subjects will also be instructed in home shoulder exercises after the first injection.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 322 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of AA4500 for the Treatment of Adhesive Capsulitis of the Shoulder
Study Start Date : November 2013
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Collagenase Clostridium Histolyticum
Up to 3 injections of .58 mg/1 mL of collagenase clostridium histolyticum (CCH), minimum of 21 days apart and home shoulder exercise.
Biological: Collagenase Clostridium Histolyticum
Treatment of Adhesive Capsulitis
Other Names:
  • AA4500
  • Xiaflex
  • Xiapex

Placebo Comparator: Placebo
Up to 3 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise.
Other: Placebo
Placebo injection




Primary Outcome Measures :
  1. Change From Baseline to Day 95 in Active Forward Flexion [ Time Frame: Baseline, day 95 ]
    Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder


Secondary Outcome Measures :
  1. Change From Baseline to Day 95 in Adapted American Shoulder and Elbow Surgeons (ASES) Function Subscale [ Time Frame: Baseline, day 95 ]
    Function subscale score ranging from 0-50, with 0 being most dysfunctional, derived from participant assessment of ability to do 10 activities with affected shoulder/arm where 0=unable to do to, 1=very difficult to do, 2=somewhat difficult, and 3=not difficult, and calculated as (cumulative total score for the 10 activity items) × (5/3); adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation (United States adapted version).

  2. Change From Baseline to Day 95 in Pain With Movement Using 11-point Numeric Rating Scale (NRS) [ Time Frame: Baseline, day 95 ]
    Participant assessment of pain in response to "How bad is the pain upon movement of your affected shoulder at its worst in the last 24 hours?" using an 11-point NRS where 0=no pain at all and 10=pain as bad as it can be.

  3. Change From Baseline to Day 95 in Active Abduction [ Time Frame: Baseline, day 95 ]
    AROM measurement using a goniometer to assess abduction in the affected shoulder

  4. Change From Baseline to Day 95 in Passive Forward Flexion [ Time Frame: Baseline, day 95 ]
    Passive range of motion (PROM) measurement using a goniometer to assess forward flexion in the affected shoulder

  5. Change From Baseline to Day 95 in Passive Abduction [ Time Frame: Baseline, day 95 ]
    PROM measurement using a goniometer to assess abduction in the affected shoulder

  6. Change From Baseline to Day 95 in Active Internal Rotation [ Time Frame: Baseline, day 95 ]
    AROM measurement using a goniometer to assess internal rotation in the affected shoulder

  7. Change From Baseline to Day 95 in Active External Rotation [ Time Frame: Baseline, day 95 ]
    AROM measurement using a goniometer to assess external rotation in the affected shoulder

  8. Change From Baseline to Day 95 in Passive Internal Rotation [ Time Frame: Baseline, day 95 ]
    PROM measurement using a goniometer to assess internal rotation in the affected shoulder

  9. Change From Baseline to Day 95 in Passive External Rotation [ Time Frame: Baseline, day 95 ]
    PROM measurement using a goniometer to assess external rotation in the affected shoulder

  10. Change From Baseline to Day 95 in Adapted ASES Pain Subscale [ Time Frame: Baseline, day 95 ]
    Pain subscale score ranging from 0-50, with 0 being greatest pain, derived from participant overall assessment of pain in response to "How bad is the pain in your affected shoulder today?" using an 11-point NRS where 0=no pain at all and 10=pain as bad as it can be and calculated as (10 - NRS score) x 5; adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation

  11. Subject Satisfaction With Treatment at Day 95 [ Time Frame: Day 95 ]
    Participant assessment of satisfaction with treatment rated as very satisfied, quite satisfied, neither satisfied nor dissatisfied, quite dissatisfied, or very dissatisfied.

  12. Investigator Assessment of Improvement With Treatment at Day 95 [ Time Frame: Day 95 ]
    Investigator assessment of degree of improvement in severity of the participant's treated shoulder compared with screening rated as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.



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.


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

Inclusion Criteria:

  • Unilateral idiopathic adhesive capsulitis of one shoulder for at least 3 months but not more than 12 months (Frozen Stage)
  • Normal range of motion in the contralateral shoulder
  • Restricted active range of motion (AROM) in the affected shoulder defined as: a deficit of at least 60 degrees in total AROM in the affected shoulder as compared with the total AROM in the contralateral shoulder and a deficit of at least 30 degrees in AROM in at least one of the following planes as compared with the contralateral shoulder:

    • Forward flexion
    • Abduction
    • External rotation with the elbow up to 90 degrees abduction
    • Internal rotation with the elbow up to 90 degrees abduction

Exclusion Criteria:

  • Has received treatment for adhesive capsulitis or is planning to receive treatment for adhesive capsulitis at any time during the study including but not limited to:

    • physical therapy or acupuncture within 2 weeks before the first injection of study drug
    • intra-articular or intrabursal injection(s) of lidocaine; suprascapular nerve blocks; corticosteroids, electroanalgesic and/or thermoanalgesic modalities within 1 month before the screening visit
    • intra-articular or intrabursal injection(s) of sodium hyaluronate and/or glenohumeral distension arthrography within 3 months before the screening visit
    • surgical intervention (including shoulder manipulation under anesthesia) at any time
  • Has any of the following conditions, as determined by investigator to be potentially confounding to the evaluation of safety and efficacy:

    • Adhesive capsulitis as a result of traumatic injury (ie, direct injury to the shoulder such as fracture of the humerus or clavicle immediately preceding the onset of this episode of adhesive capsulitis). Traumatic events in the past that are not temporally related to the onset of this episode of adhesive capsulitis would not necessarily exclude a subject from participating in the study.
    • Active subacromial impingement in the affected shoulder
    • Calcified tendonitis in the affected shoulder
    • Glenohumeral joint arthritis in the affected shoulder
    • Arthrosis of the affected shoulder
    • Chondrolysis of the affected shoulder
    • Subscapularis tendon rupture of the affected shoulder
    • Other rotator cuff injuries of the affected shoulder
    • Uncontrolled hypertension
    • Uncontrolled diabetes
    • Uncontrolled thyroid disease
    • History of thrombosis or post-thrombosis syndrome
    • Physical impairment that would preclude performing the protocol defined exercises
    • Active infection in area to be treated
    • Clinically significant neurological disease
    • Bleeding disorder
    • Chronic use of anticoagulation medications and the subject cannot be cleared medically to stop taking medication for 7 days prior to each injection. Less than or equal to 150 mg aspirin is allowed during the study.
    • Known active hepatitis A, B, or C
    • Other significant medical condition (eg, morbid obesity, cervical disc disease), which in the investigator's opinion would make the subject unsuitable for enrollment in the study
  • Has received oral or intravenous steroids for any reason within 3 weeks before the screening visit
  • Has received an investigational drug or treatment within 30 days before the first dose of study drug.
  • Has a known allergy to collagenase or any other excipient of AA4500 or any other procedural medication.
  • Has, at any time, received collagenase for the treatment of adhesive capsulitis.
  • Is unable to undergo an x-ray or MRI (contraindication) evaluation of the affected shoulder.
  • Is planning to be treated with commercial XIAFLEX at any time during the study.

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): NCT02006719


  Hide Study Locations
Locations
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United States, Alabama
Alabama Orthopaedic Center-Research
Birmingham, Alabama, United States, 35209
Coastal Clinical Research
Mobile, Alabama, United States, 36608
United States, Arizona
Arizona Research Center, Inc.
Phoenix, Arizona, United States, 85023
United States, California
Advance Med Clinical Research
Carlsbad, California, United States, 92008
Triwest Research Associates
El Cajon, California, United States, 92020
Core Orthopedic Medical Center
Encinitas, California, United States, 92024
Temecula Rheumatology & Internal Medicine
Murrieta, California, United States, 92563
Clearview Medical Research
Santa Clarita, California, United States, 91350
United States, Colorado
Colorado Orthopedic Consultants, PC
Englewood, Colorado, United States, 80110
United States, Florida
Florida Research Associates
DeLand, Florida, United States, 32720
Shrock Orthopedic Research, LLC
Fort Lauderdale, Florida, United States, 33316
Jewett Orthopedic Clinic
Orlando, Florida, United States, 32822
Clinical Research of West Florida
Tampa, Florida, United States, 33603
United States, Georgia
Non-Surgical Orthopedics, P.C. / Georgia Institute for Clinical Research, LLC
Marietta, Georgia, United States, 30060
United States, Idaho
Injury Care Medical Center
Boise, Idaho, United States, 83713
United States, Illinois
Rockford Orthopedic Associates
Rockford, Illinois, United States, 61107
Rockford Orthopedics Associates
Rockford, Illinois, United States, 61114
United States, Indiana
Indiana Hand to Shoulder Center
Indianapolis, Indiana, United States, 46260
United States, Kansas
PRN of Kansas
Wichita, Kansas, United States, 67203
United States, Kentucky
Central Kentucky Research Associates
Lexington, Kentucky, United States, 40509
United States, Louisiana
Bone and Joint Clinic
Gretna, Louisiana, United States, 70056
MedPharmics, LLC
Metairie, Louisiana, United States, 70006
United States, Maryland
Arthritis and Rheumatism Associates, PC
Wheaton, Maryland, United States, 20902
United States, Montana
Great Falls Clinic
Great Falls, Montana, United States, 59405
United States, Nevada
Nevada Orthopedic & Spine Center
Las Vegas, Nevada, United States, 89128
United States, New York
Stony Brook University Medical Center (SUNY)
Stony Brook, New York, United States, 11794
United States, North Carolina
Triangle Orthopedic Associates, PA
Durham, North Carolina, United States, 27704
Wake Research Associates
Raleigh, North Carolina, United States, 27612
United States, Oregon
The Neuromusculoskeletal Center of the Cascades d.b.a. The Center
Bend, Oregon, United States, 97701
United States, Pennsylvania
Blair Orthopedic Associates, Inc.
Altoona, Pennsylvania, United States, 16602
University of Pennsylvania Penn Orthopaedics
Philadelphia, Pennsylvania, United States, 19087
United States, Texas
Texas Orthopedic Specialist
Bedford, Texas, United States, 76021
Centex Studies
Houston, Texas, United States, 77062
United States, Virginia
Commonwealth Orthopaedics & Rehabilitation
Arlington, Virginia, United States, 22205
Danville Orthopedic Clinic, Inc.
Danville, Virginia, United States, 24541
Australia, Victoria
Sports Medicine Professionals
Richmond, Victoria, Australia, 3121
Australia
Hunter Clinical Research
NSW, Australia
Royal Prince Alfred
NSW, Australia
St George Hospital
NSW, Australia
Peninsula Private Hospital
Queensland, Australia
QPharm
Queensland, Australia
Menzies Research Institute
Tasmania, Australia
Emeritus Research
VIC, Australia
Epworth Hospital
VIC, Australia
Repatriation Hospital
VIC, Australia
Hand and Upper Limb Centre
WA, Australia
Sponsors and Collaborators
Endo Pharmaceuticals
Investigators
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Study Director: Neil H Schusterman, MD FACP Endo Pharmaceuticals

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Responsible Party: Endo Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02006719     History of Changes
Other Study ID Numbers: AUX-CC-871
First Posted: December 10, 2013    Key Record Dates
Results First Posted: May 25, 2017
Last Update Posted: October 5, 2017
Last Verified: September 2017

Keywords provided by Endo Pharmaceuticals:
Adhesive Capsulitis
Frozen Shoulder
Shoulder Range of Motion limitation
Shoulder Pain

Additional relevant MeSH terms:
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Bursitis
Joint Diseases
Musculoskeletal Diseases