Trial Outcomes & Findings for Clinical Study for the Treatment of Adhesive Capsulitis of the Shoulder (NCT NCT02006719)

NCT ID: NCT02006719

Last Updated: 2017-10-05

Results Overview

Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 322 participants
• Primary outcome timeframe: Baseline, day 95
• Results posted on: 2017-10-05

Participant Flow

Participant milestones

Measure	AA4500 Up to 3 injections of 0.58 mg/1 mL collagenase clostridium histolyticum (AA4500), minimum of 21 days apart and home shoulder exercise	Placebo Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Study STARTED	237	85
Overall Study COMPLETED	219	80
Overall Study NOT COMPLETED	18	5

Reasons for withdrawal

Measure	AA4500 Up to 3 injections of 0.58 mg/1 mL collagenase clostridium histolyticum (AA4500), minimum of 21 days apart and home shoulder exercise	Placebo Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Study Withdrawal by Subject	10	2
Overall Study Lost to Follow-up	5	1
Overall Study Protocol Violation	2	0
Overall Study Adverse Event	1	1
Overall Study Other/Unknown	0	1

Baseline Characteristics

Clinical Study for the Treatment of Adhesive Capsulitis of the Shoulder

Baseline characteristics by cohort

Measure	AA4500 n=237 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=84 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise	Total n=321 Participants Total of all reporting groups
Age, Continuous	53.0 years n=5 Participants	51.0 years n=7 Participants	52.0 years n=5 Participants
Age, Customized <45	30 Participants n=5 Participants	14 Participants n=7 Participants	44 Participants n=5 Participants
Age, Customized 45-54	114 Participants n=5 Participants	44 Participants n=7 Participants	158 Participants n=5 Participants
Age, Customized 55-64	75 Participants n=5 Participants	23 Participants n=7 Participants	98 Participants n=5 Participants
Age, Customized 65-74	17 Participants n=5 Participants	3 Participants n=7 Participants	20 Participants n=5 Participants
Age, Customized ≥75	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	162 Participants n=5 Participants	60 Participants n=7 Participants	222 Participants n=5 Participants
Sex: Female, Male Male	75 Participants n=5 Participants	24 Participants n=7 Participants	99 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	4 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	220 Participants n=5 Participants	80 Participants n=7 Participants	300 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	22 Participants n=5 Participants	7 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) White	205 Participants n=5 Participants	72 Participants n=7 Participants	277 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, day 95

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 (1 participant excluded); 25 participants missing either baseline or day 95 active forward flexion measurement also excluded

Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder

Outcome measures

Measure	AA4500 n=217 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=79 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Change From Baseline to Day 95 in Active Forward Flexion	41.0 degrees Standard Deviation 28.89	35.9 degrees Standard Deviation 23.36

SECONDARY outcome

Timeframe: Baseline, day 95

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 (1 participant excluded); 34 participants missing either baseline or day 95 function subscale scores also excluded

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).

Outcome measures

Measure	AA4500 n=211 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=76 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Change From Baseline to Day 95 in Adapted American Shoulder and Elbow Surgeons (ASES) Function Subscale	17.0 units on a scale Standard Deviation 11.65	14.8 units on a scale Standard Deviation 11.14

SECONDARY outcome

Timeframe: Baseline, day 95

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 (1 participant excluded); 33 participants missing either baseline or day 95 pain with movement scores also excluded

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.

Outcome measures

Measure	AA4500 n=211 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=77 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Change From Baseline to Day 95 in Pain With Movement Using 11-point Numeric Rating Scale (NRS)	-4.4 units on a scale Standard Deviation 2.83	-3.9 units on a scale Standard Deviation 2.93

SECONDARY outcome

Timeframe: Baseline, day 95

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 (1 participant excluded); 25 participants missing either baseline or day 95 active abduction measurement also excluded

AROM measurement using a goniometer to assess abduction in the affected shoulder

Outcome measures

Measure	AA4500 n=217 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=79 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Change From Baseline to Day 95 in Active Abduction	49.0 degrees Standard Deviation 33.10	43.8 degrees Standard Deviation 30.71

SECONDARY outcome

Timeframe: Baseline, day 95

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 (1 participant excluded); 25 participants missing either baseline or day 95 active forward flexion measurement also excluded

Passive range of motion (PROM) measurement using a goniometer to assess forward flexion in the affected shoulder

Outcome measures

Measure	AA4500 n=217 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=79 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Change From Baseline to Day 95 in Passive Forward Flexion	39.3 degrees Standard Deviation 29.47	34.1 degrees Standard Deviation 22.37

SECONDARY outcome

Timeframe: Baseline, day 95

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 (1 participant excluded); 25 participants missing either baseline or day 95 passive abduction measurement also excluded

PROM measurement using a goniometer to assess abduction in the affected shoulder

Outcome measures

Measure	AA4500 n=217 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=79 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Change From Baseline to Day 95 in Passive Abduction	45.4 degrees Standard Deviation 33.69	42.8 degrees Standard Deviation 32.12

SECONDARY outcome

Timeframe: Baseline, day 95

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 (1 participant excluded); 25 participants missing either baseline or day 95 active internal rotation measurement also excluded

AROM measurement using a goniometer to assess internal rotation in the affected shoulder

Outcome measures

Measure	AA4500 n=217 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=79 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Change From Baseline to Day 95 in Active Internal Rotation	23.1 degrees Standard Deviation 25.21	20.9 degrees Standard Deviation 23.58

SECONDARY outcome

Timeframe: Baseline, day 95

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 (1 participant excluded); 25 participants missing either baseline or day 95 active external rotation measurement also excluded

AROM measurement using a goniometer to assess external rotation in the affected shoulder

Outcome measures

Measure	AA4500 n=217 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=79 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Change From Baseline to Day 95 in Active External Rotation	28.6 degrees Standard Deviation 21.30	26.1 degrees Standard Deviation 22.67

SECONDARY outcome

Timeframe: Baseline, day 95

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 (1 participant excluded); 25 participants missing either baseline or day 95 passive internal rotation measurement also excluded

PROM measurement using a goniometer to assess internal rotation in the affected shoulder

Outcome measures

Measure	AA4500 n=217 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=79 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Change From Baseline to Day 95 in Passive Internal Rotation	24.1 degrees Standard Deviation 23.77	20.3 degrees Standard Deviation 23.61

SECONDARY outcome

Timeframe: Baseline, day 95

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 (1 participant excluded); 25 participants missing either baseline or day 95 passive external rotation measurement also excluded

PROM measurement using a goniometer to assess external rotation in the affected shoulder

Outcome measures

Measure	AA4500 n=217 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=79 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Change From Baseline to Day 95 in Passive External Rotation	24.8 degrees Standard Deviation 22.31	24.4 degrees Standard Deviation 26.16

SECONDARY outcome

Timeframe: Baseline, day 95

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 (1 participant excluded); 33 participants missing either baseline or day 95 pain subscale scores also excluded

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

Outcome measures

Measure	AA4500 n=211 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=77 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Change From Baseline to Day 95 in Adapted ASES Pain Subscale	15.9 units on a scale Standard Deviation 13.46	13.5 units on a scale Standard Deviation 13.45

SECONDARY outcome

Timeframe: Day 95

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 (1 participant excluded); 11 participants not completing questionnaire also excluded

Participant assessment of satisfaction with treatment rated as very satisfied, quite satisfied, neither satisfied nor dissatisfied, quite dissatisfied, or very dissatisfied.

Outcome measures

Measure	AA4500 n=229 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=81 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Subject Satisfaction With Treatment at Day 95 Very satisfied	142 participants	43 participants
Subject Satisfaction With Treatment at Day 95 Quite satisfied	38 participants	22 participants
Subject Satisfaction With Treatment at Day 95 Neither satisfied nor dissatisfied	32 participants	8 participants
Subject Satisfaction With Treatment at Day 95 Quite dissatisfied	10 participants	2 participants
Subject Satisfaction With Treatment at Day 95 Very dissatisfied	7 participants	6 participants

SECONDARY outcome

Timeframe: Day 95

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 (1 participant excluded); 10 participants also excluded for incomplete questionnaire

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.

Outcome measures

Measure	AA4500 n=229 Participants Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=82 Participants Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Investigator Assessment of Improvement With Treatment at Day 95 Minimally worse	6 participants	0 participants
Investigator Assessment of Improvement With Treatment at Day 95 Very much improved	94 participants	27 participants
Investigator Assessment of Improvement With Treatment at Day 95 Much improved	73 participants	31 participants
Investigator Assessment of Improvement With Treatment at Day 95 Minimally improved	41 participants	16 participants
Investigator Assessment of Improvement With Treatment at Day 95 No change	13 participants	8 participants
Investigator Assessment of Improvement With Treatment at Day 95 Much worse	1 participants	0 participants
Investigator Assessment of Improvement With Treatment at Day 95 Very much worse	1 participants	0 participants

Adverse Events

AA4500

Serious events: 4 serious events

Other events: 188 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Measure	AA4500 n=237 participants at risk Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=84 participants at risk Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Cardiac disorders Atrial fibrilation	0.42% 1/237 • Number of events 1 • 130 days (up to 28 day screening period and 95±7 day study period)	0.00% 0/84 • 130 days (up to 28 day screening period and 95±7 day study period)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	0.42% 1/237 • Number of events 1 • 130 days (up to 28 day screening period and 95±7 day study period)	0.00% 0/84 • 130 days (up to 28 day screening period and 95±7 day study period)
Injury, poisoning and procedural complications Overdose	0.42% 1/237 • Number of events 1 • 130 days (up to 28 day screening period and 95±7 day study period)	0.00% 0/84 • 130 days (up to 28 day screening period and 95±7 day study period)
Injury, poisoning and procedural complications Post procedural bile leak	0.42% 1/237 • Number of events 1 • 130 days (up to 28 day screening period and 95±7 day study period)	0.00% 0/84 • 130 days (up to 28 day screening period and 95±7 day study period)
Injury, poisoning and procedural complications Procedural pain	0.42% 1/237 • Number of events 1 • 130 days (up to 28 day screening period and 95±7 day study period)	0.00% 0/84 • 130 days (up to 28 day screening period and 95±7 day study period)
Gastrointestinal disorders Gastric ulcer	0.00% 0/237 • 130 days (up to 28 day screening period and 95±7 day study period)	1.2% 1/84 • Number of events 1 • 130 days (up to 28 day screening period and 95±7 day study period)

Other adverse events

Measure	AA4500 n=237 participants at risk Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise	Placebo n=84 participants at risk Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Musculoskeletal and connective tissue disorders Musculoskeletal pain	38.0% 90/237 • Number of events 138 • 130 days (up to 28 day screening period and 95±7 day study period)	21.4% 18/84 • Number of events 24 • 130 days (up to 28 day screening period and 95±7 day study period)
Injury, poisoning and procedural complications Contusion	30.0% 71/237 • Number of events 106 • 130 days (up to 28 day screening period and 95±7 day study period)	2.4% 2/84 • Number of events 2 • 130 days (up to 28 day screening period and 95±7 day study period)
General disorders Injection site bruising	21.9% 52/237 • Number of events 65 • 130 days (up to 28 day screening period and 95±7 day study period)	11.9% 10/84 • Number of events 13 • 130 days (up to 28 day screening period and 95±7 day study period)
General disorders Injection site pain	21.1% 50/237 • Number of events 77 • 130 days (up to 28 day screening period and 95±7 day study period)	13.1% 11/84 • Number of events 17 • 130 days (up to 28 day screening period and 95±7 day study period)
Skin and subcutaneous tissue disorders Ecchymosis	19.8% 47/237 • Number of events 69 • 130 days (up to 28 day screening period and 95±7 day study period)	3.6% 3/84 • Number of events 4 • 130 days (up to 28 day screening period and 95±7 day study period)
General disorders Localised oedema	8.4% 20/237 • Number of events 28 • 130 days (up to 28 day screening period and 95±7 day study period)	1.2% 1/84 • Number of events 1 • 130 days (up to 28 day screening period and 95±7 day study period)
Musculoskeletal and connective tissue disorders Pain in extremity	5.5% 13/237 • Number of events 16 • 130 days (up to 28 day screening period and 95±7 day study period)	4.8% 4/84 • Number of events 5 • 130 days (up to 28 day screening period and 95±7 day study period)
Skin and subcutaneous tissue disorders Pruritus	5.1% 12/237 • Number of events 15 • 130 days (up to 28 day screening period and 95±7 day study period)	0.00% 0/84 • 130 days (up to 28 day screening period and 95±7 day study period)

Additional Information

Clinical Trial Coordinator

Endo Pharmaceuticals Inc.

Email: clinicalsite.inquiries@endo.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place