Adhesive Capsulitis, Frozen Shoulder
Conditions
Brief summary
The objectives of this study are to assess the safety, effectiveness, and immunogenicity of AA4500 in the treatment of adhesive capsulitis.
Detailed description
This study is a Phase 2a, open-label, dose-ranging study of the safety and effectiveness 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 30 days before injection of study drug. Approximately 50 adult women and men are to be enrolled in this study. Following screening and determination of study eligibility, Assignment to Cohorts 1-4 is sequential. Subjects assigned to Cohorts 1 through 4 may receive up to 3 injections of AA4500 according to cohort assignment. Each injection will be separated by a minimum of 21 days. Subjects assigned to Cohort 5 will receive home shoulder exercises only, while subjects assigned to Cohorts 1-4 will receive AA4500 and home shoulder exercises. Subjects in Cohort 5 will be offered physical therapy sessions for a period of 2 months following completion of the study. Dosing will range from 0.29 mg to 0.58 mg with varying volumes.
Interventions
BIOLOGICALAA4500 0.29 mg/1 mL
treatment of adhesive capsulitis
BIOLOGICALAA4500 0.58 mg/2 mL
treatment of adhesive capsulitis
BIOLOGICALAA4500 0.58 mg/1 mL
treatment of adhesive capsulitis
BIOLOGICALAA4500 0.58 mg/0.5 mL
treatment of adhesive capsulitis
OTHERShoulder exercises
Home shoulder exercises, minimum of 3 times per day
Sponsors
Endo Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be a male or female and be greater than or equal to 18 years of age 2. If a female of childbearing potential, have a negative urine pregnancy test and be using an effective contraception method (ie, abstinence, intrauterine device (IUD), hormonal (estrogen/progestin) contraceptives, or barrier control) for at least one menstrual cycle prior to study enrollment and for one menstrual cycle following end of study, or be surgically sterile 3. Have unilateral idiopathic adhesive capsulitis of one shoulder for at least 3 months but not more than 12 months before the screening visit and be in Stage 2 (frozen or adhesive stage), as determined by the investigator 4. Have normal range of motion in the contralateral shoulder, as determined by the investigator 5. Have 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 6. Voluntarily sign and date an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). The subject must also sign an authorization form to allow disclosure of his protected health information (PHI). The PHI authorization form and informed consent form may be an integrated form or may be separate forms depending on the institution. 7. Be able to complete and understand the various rating instruments in English.
Exclusion criteria
1. Is a pregnant or lactating female or female intending to become pregnant during the study 2. Is a male who intends to father a child during the study 3. 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 AA4500 * 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 within 3 months before the screening visit * glenohumeral distension arthrography and/or surgical intervention (including shoulder manipulation under anesthesia) at any time 4. Has any of the following conditions, as determined by the investigator: * Adhesive capsulitis as a result of traumatic injury * Pain in the affected shoulder at rest that is greater than or equal to 4 on the 11-point pain scale * 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 * Coagulation disorder, using anticoagulant (except for less than or equal to 150 mg aspirin) within 7 days prior to each injection day * Known active hepatitis B or C (history of hepatitis A permitted) * 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 5. Is unwilling or unable to cooperate with the requirements of the study including completion of all scheduled study visits. 6. Has received oral or intravenous steroids for any reason within 3 weeks before the screening visit 7. Has received an investigational drug or treatment within 30 days before the first dose of study drug. 8. Has a known systemic allergy to collagenase or any other excipient of AA4500 or any other procedural medication. 9. Has, at any time, received collagenase for the treatment of adhesive capsulitis. 10. Is unable to undergo an x-ray or MRI (contraindication) evaluation of the affected shoulder. 11. Is planning to be treated with commercial Xiaflex at any time during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 92 in Active Forward Flexion | Baseline, Day 92 | Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 92 in Active Abduction | Baseline, Day 92 | AROM measurement using a goniometer to assess abduction in the affected shoulder |
| Change From Baseline to Day 92 in Passive Abduction | Baseline, Day 92 | PROM measurement using a goniometer to assess abduction in the affected shoulder |
| Change From Baseline to Day 92 in Active External Rotation | Baseline, Day 92 | AROM measurement using a goniometer to assess external rotation in the affected shoulder |
| Change From Baseline to Day 92 in Passive External Rotation | Baseline, Day 92 | PROM measurement using a goniometer to assess external rotation in the affected shoulder |
| Change From Baseline to Day 92 in Active Internal Rotation | Baseline, Day 92 | AROM measurement using a goniometer to assess internal rotation with the elbow up to 90° abduction in the affected shoulder |
| Change From Baseline to Day 92 in Passive Forward Flexion | Baseline, Day 92 | Passive range of motion (PROM) measurement using a goniometer to assess forward flexion in the affected shoulder |
| Change From Baseline to Day 92 in American Shoulder and Elbow Surgeons (ASES) Composite Score | Baseline, Day 92 | Composite score ranging from 0-100, with 0 being worst pain and function loss, derived from the sum of the scores from pain subscale (11-point NRS where 0=no pain at all and 10=pain) and function subscale (activity questionnaire where 0=unable to do to, 1=very difficult to do, 2=somewhat difficult, and 3=not difficult); adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation |
| Change From Baseline to Day 92 in ASES Pain Subscale | Baseline, Day 92 | Pain subscale score ranging from 0-50, with 0 being greatest pain, derived from participant assessment of pain in response to How bad is the pain in your affected shoulder today? on an 11-point numerical rating scale (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 |
| Change From Baseline to Day 92 in ASES Function Subscale | Baseline, Day 92 | 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 |
| Subject Satisfaction With Treatment at Day 92 | Day 92 | Participant assessment of satisfaction with treatment rated as very satisfied, quite satisfied, neither satisfied nor dissatisfied, quite dissatisfied, or very dissatisfied. |
| Investigator Assessment of Improvement With Treatment at Day 92 | Day 92 | 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. |
| Change From Baseline to Day 92 in Passive Internal Rotation | Baseline, Day 92 | PROM measurement using a goniometer to assess internal rotation with the elbow up to 90° abduction in the affected shoulder |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AA4500 0.29 mg/1 mL Up to 3 injections of AA4500 0.29 mg/1 mL
Shoulder exercises: Home shoulder exercises, minimum of 3 times per day | 10 |
| AA4500 0.58 mg/2 mL Up to 3 injections of AA4500 0.58 mg/2 mL
Shoulder exercises: Home shoulder exercises, minimum of 3 times per day | 10 |
| AA4500 0.58 mg/1 mL Up to 3 injections of AA4500 0.58 mg/1 mL
Shoulder exercises: Home shoulder exercises, minimum of 3 times per day | 10 |
| AA4500 0.58 mg/0.5 mL Up to 3 injections of AA4500 0.58 mg/0.5 mL
Shoulder exercises: Home shoulder exercises, minimum of 3 times per day | 10 |
| Shoulder Exercises Only Home shoulder exercises for 64 days
Shoulder exercises: Home shoulder exercises, minimum of 3 times per day | 10 |
| Total | 50 |
Baseline characteristics
| Characteristic | AA4500 0.29 mg/1 mL | Total | Shoulder Exercises Only | AA4500 0.58 mg/0.5 mL | AA4500 0.58 mg/1 mL | AA4500 0.58 mg/2 mL |
|---|---|---|---|---|---|---|
| Age, Continuous | 49.1 years STANDARD_DEVIATION 4.93 | 54.0 years STANDARD_DEVIATION 7.6 | 55.1 years STANDARD_DEVIATION 7.02 | 53.2 years STANDARD_DEVIATION 5.71 | 58.4 years STANDARD_DEVIATION 8.97 | 54.1 years STANDARD_DEVIATION 8.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 48 Participants | 10 Participants | 10 Participants | 10 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 48 Participants | 10 Participants | 10 Participants | 9 Participants | 10 Participants |
| Region of Enrollment United States | 10 participants | 50 participants | 10 participants | 10 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 8 Participants | 40 Participants | 7 Participants | 8 Participants | 9 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 10 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 9 / 10 | 9 / 10 | 10 / 10 | 10 / 10 | 2 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Change From Baseline to Day 92 in Active Forward Flexion
Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder
Time frame: Baseline, Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Change From Baseline to Day 92 in Active Forward Flexion | 22.9 degrees | Standard Deviation 13.83 |
| AA4500 0.58 mg/2 mL | Change From Baseline to Day 92 in Active Forward Flexion | 37.5 degrees | Standard Deviation 22.89 |
| AA4500 0.58 mg/1 mL | Change From Baseline to Day 92 in Active Forward Flexion | 42.9 degrees | Standard Deviation 30.64 |
| AA4500 0.58 mg/0.5 mL | Change From Baseline to Day 92 in Active Forward Flexion | 23.8 degrees | Standard Deviation 41.97 |
| Shoulder Exercises Only | Change From Baseline to Day 92 in Active Forward Flexion | 12.0 degrees | Standard Deviation 12.68 |
Secondary
Change From Baseline to Day 92 in Active Abduction
AROM measurement using a goniometer to assess abduction in the affected shoulder
Time frame: Baseline, Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Change From Baseline to Day 92 in Active Abduction | 28.4 degrees | Standard Deviation 15.81 |
| AA4500 0.58 mg/2 mL | Change From Baseline to Day 92 in Active Abduction | 36.0 degrees | Standard Deviation 32.94 |
| AA4500 0.58 mg/1 mL | Change From Baseline to Day 92 in Active Abduction | 53.7 degrees | Standard Deviation 27.59 |
| AA4500 0.58 mg/0.5 mL | Change From Baseline to Day 92 in Active Abduction | 35.8 degrees | Standard Deviation 41.02 |
| Shoulder Exercises Only | Change From Baseline to Day 92 in Active Abduction | 16.7 degrees | Standard Deviation 8.06 |
Secondary
Change From Baseline to Day 92 in Active External Rotation
AROM measurement using a goniometer to assess external rotation in the affected shoulder
Time frame: Baseline, Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Change From Baseline to Day 92 in Active External Rotation | 24.8 degrees | Standard Deviation 13.39 |
| AA4500 0.58 mg/2 mL | Change From Baseline to Day 92 in Active External Rotation | 19.7 degrees | Standard Deviation 27.49 |
| AA4500 0.58 mg/1 mL | Change From Baseline to Day 92 in Active External Rotation | 16.6 degrees | Standard Deviation 16.79 |
| AA4500 0.58 mg/0.5 mL | Change From Baseline to Day 92 in Active External Rotation | 7.4 degrees | Standard Deviation 29.15 |
| Shoulder Exercises Only | Change From Baseline to Day 92 in Active External Rotation | 6.0 degrees | Standard Deviation 27.87 |
Secondary
Change From Baseline to Day 92 in Active Internal Rotation
AROM measurement using a goniometer to assess internal rotation with the elbow up to 90° abduction in the affected shoulder
Time frame: Baseline, Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Change From Baseline to Day 92 in Active Internal Rotation | 8.1 degrees | Standard Deviation 14.12 |
| AA4500 0.58 mg/2 mL | Change From Baseline to Day 92 in Active Internal Rotation | 13.0 degrees | Standard Deviation 20.85 |
| AA4500 0.58 mg/1 mL | Change From Baseline to Day 92 in Active Internal Rotation | 9.5 degrees | Standard Deviation 26.87 |
| AA4500 0.58 mg/0.5 mL | Change From Baseline to Day 92 in Active Internal Rotation | 17.4 degrees | Standard Deviation 24.43 |
| Shoulder Exercises Only | Change From Baseline to Day 92 in Active Internal Rotation | 1.2 degrees | Standard Deviation 20.92 |
Secondary
Change From Baseline to Day 92 in American Shoulder and Elbow Surgeons (ASES) Composite Score
Composite score ranging from 0-100, with 0 being worst pain and function loss, derived from the sum of the scores from pain subscale (11-point NRS where 0=no pain at all and 10=pain) and function subscale (activity questionnaire where 0=unable to do to, 1=very difficult to do, 2=somewhat difficult, and 3=not difficult); adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation
Time frame: Baseline, Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Change From Baseline to Day 92 in American Shoulder and Elbow Surgeons (ASES) Composite Score | 26.9 units on a scale | Standard Deviation 13.17 |
| AA4500 0.58 mg/2 mL | Change From Baseline to Day 92 in American Shoulder and Elbow Surgeons (ASES) Composite Score | 41.6 units on a scale | Standard Deviation 18.99 |
| AA4500 0.58 mg/1 mL | Change From Baseline to Day 92 in American Shoulder and Elbow Surgeons (ASES) Composite Score | 35.9 units on a scale | Standard Deviation 24.33 |
| AA4500 0.58 mg/0.5 mL | Change From Baseline to Day 92 in American Shoulder and Elbow Surgeons (ASES) Composite Score | 19.3 units on a scale | Standard Deviation 24.29 |
| Shoulder Exercises Only | Change From Baseline to Day 92 in American Shoulder and Elbow Surgeons (ASES) Composite Score | 9.9 units on a scale | Standard Deviation 15.84 |
Secondary
Change From Baseline to Day 92 in ASES Function Subscale
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
Time frame: Baseline, Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Change From Baseline to Day 92 in ASES Function Subscale | 17.4 units on a scale | Standard Deviation 8.72 |
| AA4500 0.58 mg/2 mL | Change From Baseline to Day 92 in ASES Function Subscale | 26.0 units on a scale | Standard Deviation 10.98 |
| AA4500 0.58 mg/1 mL | Change From Baseline to Day 92 in ASES Function Subscale | 19.2 units on a scale | Standard Deviation 12.36 |
| AA4500 0.58 mg/0.5 mL | Change From Baseline to Day 92 in ASES Function Subscale | 11.3 units on a scale | Standard Deviation 13.53 |
| Shoulder Exercises Only | Change From Baseline to Day 92 in ASES Function Subscale | 8.4 units on a scale | Standard Deviation 5.85 |
Secondary
Change From Baseline to Day 92 in ASES Pain Subscale
Pain subscale score ranging from 0-50, with 0 being greatest pain, derived from participant assessment of pain in response to How bad is the pain in your affected shoulder today? on an 11-point numerical rating scale (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
Time frame: Baseline, Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Change From Baseline to Day 92 in ASES Pain Subscale | 10.0 units on a scale | Standard Deviation 11.06 |
| AA4500 0.58 mg/2 mL | Change From Baseline to Day 92 in ASES Pain Subscale | 15.5 units on a scale | Standard Deviation 13.22 |
| AA4500 0.58 mg/1 mL | Change From Baseline to Day 92 in ASES Pain Subscale | 15.5 units on a scale | Standard Deviation 14.99 |
| AA4500 0.58 mg/0.5 mL | Change From Baseline to Day 92 in ASES Pain Subscale | 8.0 units on a scale | Standard Deviation 12.52 |
| Shoulder Exercises Only | Change From Baseline to Day 92 in ASES Pain Subscale | 1.5 units on a scale | Standard Deviation 11.32 |
Secondary
Change From Baseline to Day 92 in Passive Abduction
PROM measurement using a goniometer to assess abduction in the affected shoulder
Time frame: Baseline, Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Change From Baseline to Day 92 in Passive Abduction | 28.6 degrees | Standard Deviation 15.69 |
| AA4500 0.58 mg/2 mL | Change From Baseline to Day 92 in Passive Abduction | 44.8 degrees | Standard Deviation 34.69 |
| AA4500 0.58 mg/1 mL | Change From Baseline to Day 92 in Passive Abduction | 56.1 degrees | Standard Deviation 30.05 |
| AA4500 0.58 mg/0.5 mL | Change From Baseline to Day 92 in Passive Abduction | 18.0 degrees | Standard Deviation 40.87 |
| Shoulder Exercises Only | Change From Baseline to Day 92 in Passive Abduction | 24.3 degrees | Standard Deviation 29.69 |
Secondary
Change From Baseline to Day 92 in Passive External Rotation
PROM measurement using a goniometer to assess external rotation in the affected shoulder
Time frame: Baseline, Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Change From Baseline to Day 92 in Passive External Rotation | 20.0 degrees | Standard Deviation 9.64 |
| AA4500 0.58 mg/2 mL | Change From Baseline to Day 92 in Passive External Rotation | 19.3 degrees | Standard Deviation 24.57 |
| AA4500 0.58 mg/1 mL | Change From Baseline to Day 92 in Passive External Rotation | 40.9 degrees | Standard Deviation 33.71 |
| AA4500 0.58 mg/0.5 mL | Change From Baseline to Day 92 in Passive External Rotation | 9.1 degrees | Standard Deviation 29.32 |
| Shoulder Exercises Only | Change From Baseline to Day 92 in Passive External Rotation | 10.7 degrees | Standard Deviation 20.27 |
Secondary
Change From Baseline to Day 92 in Passive Forward Flexion
Passive range of motion (PROM) measurement using a goniometer to assess forward flexion in the affected shoulder
Time frame: Baseline, Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Change From Baseline to Day 92 in Passive Forward Flexion | 21.8 degrees | Standard Deviation 11.92 |
| AA4500 0.58 mg/2 mL | Change From Baseline to Day 92 in Passive Forward Flexion | 39.1 degrees | Standard Deviation 22.13 |
| AA4500 0.58 mg/1 mL | Change From Baseline to Day 92 in Passive Forward Flexion | 46.2 degrees | Standard Deviation 20.35 |
| AA4500 0.58 mg/0.5 mL | Change From Baseline to Day 92 in Passive Forward Flexion | 10.5 degrees | Standard Deviation 23.96 |
| Shoulder Exercises Only | Change From Baseline to Day 92 in Passive Forward Flexion | 12.0 degrees | Standard Deviation 14.13 |
Secondary
Change From Baseline to Day 92 in Passive Internal Rotation
PROM measurement using a goniometer to assess internal rotation with the elbow up to 90° abduction in the affected shoulder
Time frame: Baseline, Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Change From Baseline to Day 92 in Passive Internal Rotation | 8.4 degrees | Standard Deviation 16.87 |
| AA4500 0.58 mg/2 mL | Change From Baseline to Day 92 in Passive Internal Rotation | 19.8 degrees | Standard Deviation 21.7 |
| AA4500 0.58 mg/1 mL | Change From Baseline to Day 92 in Passive Internal Rotation | 13.1 degrees | Standard Deviation 23.38 |
| AA4500 0.58 mg/0.5 mL | Change From Baseline to Day 92 in Passive Internal Rotation | 23.6 degrees | Standard Deviation 18.77 |
| Shoulder Exercises Only | Change From Baseline to Day 92 in Passive Internal Rotation | 2.9 degrees | Standard Deviation 17.55 |
Secondary
Investigator Assessment of Improvement With Treatment at Day 92
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.
Time frame: Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Very much improved | 1 Participants |
| AA4500 0.29 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Very much worse | 0 Participants |
| AA4500 0.29 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Much worse | 0 Participants |
| AA4500 0.29 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Minimally improved | 5 Participants |
| AA4500 0.29 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Much improved | 3 Participants |
| AA4500 0.29 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | No change | 1 Participants |
| AA4500 0.29 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Minimally worse | 0 Participants |
| AA4500 0.58 mg/2 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Minimally worse | 1 Participants |
| AA4500 0.58 mg/2 mL | Investigator Assessment of Improvement With Treatment at Day 92 | No change | 0 Participants |
| AA4500 0.58 mg/2 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Much improved | 2 Participants |
| AA4500 0.58 mg/2 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Very much improved | 5 Participants |
| AA4500 0.58 mg/2 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Much worse | 0 Participants |
| AA4500 0.58 mg/2 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Minimally improved | 2 Participants |
| AA4500 0.58 mg/2 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Very much worse | 0 Participants |
| AA4500 0.58 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | No change | 0 Participants |
| AA4500 0.58 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Very much improved | 7 Participants |
| AA4500 0.58 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Much improved | 2 Participants |
| AA4500 0.58 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Minimally improved | 1 Participants |
| AA4500 0.58 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Minimally worse | 0 Participants |
| AA4500 0.58 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Much worse | 0 Participants |
| AA4500 0.58 mg/1 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Very much worse | 0 Participants |
| AA4500 0.58 mg/0.5 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Minimally improved | 5 Participants |
| AA4500 0.58 mg/0.5 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Minimally worse | 0 Participants |
| AA4500 0.58 mg/0.5 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Much improved | 1 Participants |
| AA4500 0.58 mg/0.5 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Very much worse | 0 Participants |
| AA4500 0.58 mg/0.5 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Much worse | 0 Participants |
| AA4500 0.58 mg/0.5 mL | Investigator Assessment of Improvement With Treatment at Day 92 | Very much improved | 3 Participants |
| AA4500 0.58 mg/0.5 mL | Investigator Assessment of Improvement With Treatment at Day 92 | No change | 1 Participants |
| Shoulder Exercises Only | Investigator Assessment of Improvement With Treatment at Day 92 | Minimally improved | 3 Participants |
| Shoulder Exercises Only | Investigator Assessment of Improvement With Treatment at Day 92 | Very much worse | 0 Participants |
| Shoulder Exercises Only | Investigator Assessment of Improvement With Treatment at Day 92 | Much worse | 0 Participants |
| Shoulder Exercises Only | Investigator Assessment of Improvement With Treatment at Day 92 | Minimally worse | 1 Participants |
| Shoulder Exercises Only | Investigator Assessment of Improvement With Treatment at Day 92 | Much improved | 2 Participants |
| Shoulder Exercises Only | Investigator Assessment of Improvement With Treatment at Day 92 | Very much improved | 2 Participants |
| Shoulder Exercises Only | Investigator Assessment of Improvement With Treatment at Day 92 | No change | 2 Participants |
Secondary
Subject Satisfaction With Treatment at Day 92
Participant assessment of satisfaction with treatment rated as very satisfied, quite satisfied, neither satisfied nor dissatisfied, quite dissatisfied, or very dissatisfied.
Time frame: Day 92
Population: All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (AA4500 groups) or post baseline (shoulder exercises only group)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AA4500 0.29 mg/1 mL | Subject Satisfaction With Treatment at Day 92 | Quite dissatisfies | 0 Participants |
| AA4500 0.29 mg/1 mL | Subject Satisfaction With Treatment at Day 92 | Very satisfied | 4 Participants |
| AA4500 0.29 mg/1 mL | Subject Satisfaction With Treatment at Day 92 | Very dissatisfied | 0 Participants |
| AA4500 0.29 mg/1 mL | Subject Satisfaction With Treatment at Day 92 | Quite satisfied | 4 Participants |
| AA4500 0.29 mg/1 mL | Subject Satisfaction With Treatment at Day 92 | Neither satisfied nor dissatisfied | 2 Participants |
| AA4500 0.58 mg/2 mL | Subject Satisfaction With Treatment at Day 92 | Quite dissatisfies | 1 Participants |
| AA4500 0.58 mg/2 mL | Subject Satisfaction With Treatment at Day 92 | Neither satisfied nor dissatisfied | 1 Participants |
| AA4500 0.58 mg/2 mL | Subject Satisfaction With Treatment at Day 92 | Quite satisfied | 2 Participants |
| AA4500 0.58 mg/2 mL | Subject Satisfaction With Treatment at Day 92 | Very dissatisfied | 0 Participants |
| AA4500 0.58 mg/2 mL | Subject Satisfaction With Treatment at Day 92 | Very satisfied | 6 Participants |
| AA4500 0.58 mg/1 mL | Subject Satisfaction With Treatment at Day 92 | Neither satisfied nor dissatisfied | 0 Participants |
| AA4500 0.58 mg/1 mL | Subject Satisfaction With Treatment at Day 92 | Very satisfied | 8 Participants |
| AA4500 0.58 mg/1 mL | Subject Satisfaction With Treatment at Day 92 | Quite satisfied | 1 Participants |
| AA4500 0.58 mg/1 mL | Subject Satisfaction With Treatment at Day 92 | Quite dissatisfies | 1 Participants |
| AA4500 0.58 mg/1 mL | Subject Satisfaction With Treatment at Day 92 | Very dissatisfied | 0 Participants |
| AA4500 0.58 mg/0.5 mL | Subject Satisfaction With Treatment at Day 92 | Very dissatisfied | 0 Participants |
| AA4500 0.58 mg/0.5 mL | Subject Satisfaction With Treatment at Day 92 | Very satisfied | 3 Participants |
| AA4500 0.58 mg/0.5 mL | Subject Satisfaction With Treatment at Day 92 | Quite dissatisfies | 1 Participants |
| AA4500 0.58 mg/0.5 mL | Subject Satisfaction With Treatment at Day 92 | Neither satisfied nor dissatisfied | 3 Participants |
| AA4500 0.58 mg/0.5 mL | Subject Satisfaction With Treatment at Day 92 | Quite satisfied | 3 Participants |
| Shoulder Exercises Only | Subject Satisfaction With Treatment at Day 92 | Neither satisfied nor dissatisfied | 3 Participants |
| Shoulder Exercises Only | Subject Satisfaction With Treatment at Day 92 | Quite dissatisfies | 0 Participants |
| Shoulder Exercises Only | Subject Satisfaction With Treatment at Day 92 | Very satisfied | 5 Participants |
| Shoulder Exercises Only | Subject Satisfaction With Treatment at Day 92 | Very dissatisfied | 0 Participants |
| Shoulder Exercises Only | Subject Satisfaction With Treatment at Day 92 | Quite satisfied | 2 Participants |