Trial Outcomes & Findings for Cingal Study for Knee Osteoarthritis (NCT NCT01891396)

NCT ID: NCT01891396

Last Updated: 2023-06-01

Results Overview

The change in knee pain from baseline to 12 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group (ITT population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 368 participants
• Primary outcome timeframe: 12 Weeks
• Results posted on: 2023-06-01

Participant Flow

594 potential subjects were screened for the study. 226 subjects were screen failures. 368 subjects were randomized into Cingal 13-01 and all received the study injection.

The most common reason that subjects were excluded before being assigned to a study group (screen failures) was that enrollment target had been reached while subjects were in screening process. Other reasons for screen failure included radiological failures; Kellgren-Lawrence grade not meeting eligibility in the index or contralateral knee.

Participant milestones

Measure	Hyaluronic Acid and TH (Cingal®) Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 milliliter (mL) unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) Single injection of sodium hyaluronate supplied as a 4 milliliter (mL) unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 milliliter (mL) unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Overall Study STARTED	149	150	69
Overall Study Received Study Injection	149	150	69
Overall Study COMPLETED	145	145	66
Overall Study NOT COMPLETED	4	5	3

Reasons for withdrawal

Measure	Hyaluronic Acid and TH (Cingal®) Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 milliliter (mL) unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) Single injection of sodium hyaluronate supplied as a 4 milliliter (mL) unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 milliliter (mL) unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Overall Study Withdrawal by Subject	4	4	3
Overall Study Lost to Follow-up	0	1	0

Baseline Characteristics

Cingal Study for Knee Osteoarthritis

Baseline characteristics by cohort

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=150 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline n=69 Participants Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.	Total n=368 Participants Total of all reporting groups
Age, Continuous	57.52 years STANDARD_DEVIATION 8.39 • n=5 Participants	59.19 years STANDARD_DEVIATION 8.62 • n=7 Participants	58.03 years STANDARD_DEVIATION 9.02 • n=5 Participants	58.30 years STANDARD_DEVIATION 8.62 • n=4 Participants
Sex: Female, Male Female	97 Participants n=5 Participants	99 Participants n=7 Participants	51 Participants n=5 Participants	247 Participants n=4 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	51 Participants n=7 Participants	18 Participants n=5 Participants	121 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	149 Participants n=5 Participants	149 Participants n=7 Participants	69 Participants n=5 Participants	367 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: 12 Weeks

Population: Intent To Treat (ITT) Population

The change in knee pain from baseline to 12 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group (ITT population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=150 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline n=69 Participants Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (ITT)	-40.2 score on a scale Standard Error 1.7	-36.1 score on a scale Standard Error 1.6	-31.0 score on a scale Standard Error 2.3

PRIMARY outcome

Timeframe: 12 Weeks

Population: Per Protocol (PP) Population

The change in knee pain from baseline to 12 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group (PP population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=137 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=135 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline n=63 Participants Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (PP)	-40.3 score on a scale Standard Error 1.4	-35.9 score on a scale Standard Error 1.62	-32.2 score on a scale Standard Error 2.2

SECONDARY outcome

Timeframe: 1 Week

Population: Intent To Treat (ITT) Population comparing Cingal® group to Monovisc® group. Saline group is analyzed separately.

The change in knee pain from baseline to 1 week post treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (ITT population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=150 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (ITT)	-34.6 score on a scale Standard Deviation 20.8	-29.6 score on a scale Standard Deviation 21.4	—

SECONDARY outcome

Timeframe: 3 Weeks

Population: Intent To Treat (ITT) Population to compare Cingal® group to Monovisc® group. Saline group is analyzed separately.

The change in knee pain from baseline to 3 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (ITT population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the change from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=150 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (ITT)	-40.1 score on a scale Standard Deviation 20.1	-34.9 score on a scale Standard Deviation 21.7	—

SECONDARY outcome

Timeframe: 12 Weeks

Population: Intent To Treat (ITT) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

The post treatment Responder Rate at 12 weeks is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index. The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder. The criteria for response are (1) improvement in pain or physical function ≥50% and an absolute change ≥20 mm; or (2) improvement of ≥20% with an absolute change ≥10 mm in at least two of the following three categories: pain, physical function, and patient's global assessment.

A higher percentage of subjects responding indicates a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=69 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
OMERACT-OARSI Responder Index Comparing Cingal® to Saline (ITT)	92.0 percentage of subjects	81.9 percentage of subjects	—

SECONDARY outcome

Timeframe: 12 Weeks

Population: Intent To Treat (ITT) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

The change from baseline to 12 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (ITT population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 mm = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=69 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Patient Global Assessment (PGA) Comparing Cingal® to Saline (ITT)	-36.5 score on a scale Standard Error 1.6	-25.3 score on a scale Standard Error 2.4	—

SECONDARY outcome

Timeframe: 1 Week

Population: Intent To Treat (ITT) Population to compare Cingal® group to Monovisc® group. Saline group is analyzed separately.

The change from baseline to 1 week in the Patient Global Assessment (PGA) comparing the Cingal® and Monovisc® arms (ITT population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=150 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (ITT)	-32.8 score on a scale Standard Deviation 23.3	-24.7 score on a scale Standard Deviation 22.6	—

SECONDARY outcome

Timeframe: 3 Weeks

Population: Intent To Treat (ITT) Population to compare Cingal® group to Monovisc® group. Saline group is analyzed separately.

Mean change from baseline to 3 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Monovisc® arms (ITT population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=150 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (ITT)	-37.7 score on a scale Standard Deviation 23.9	-32.1 score on a scale Standard Deviation 23.7	—

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

Mean change in knee pain from baseline to 26 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group. The WOMAC Pain Score is a validated 100mm visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=69 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (ITT)	-41.1 score on a scale Standard Error 1.7	-31.4 score on a scale Standard Error 2.4	—

SECONDARY outcome

Timeframe: 12 Weeks

Population: Intent To Treat (ITT) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

Mean change from baseline to 12 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=69 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Evaluator Global Assessment Comparing Cingal® to Saline (ITT)	-36.8 score on a scale Standard Error 1.5	-27.2 score on a scale Standard Error 2.8	—

SECONDARY outcome

Timeframe: 1 Week

Population: Intent To Treat (ITT) Population to compare Cingal® group to Monovisc® group. Saline group is analyzed separately.

Mean change from baseline to 1 week in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=150 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Evaluator Global Assessment Comparing Cingal® to Monovisc® (ITT)	-31.7 score on a scale Standard Deviation 20.4	-26.9 score on a scale Standard Deviation 19.7	—

SECONDARY outcome

Timeframe: 3 Week

Population: Intent To Treat (ITT) Population to compare Cingal® group to Monovisc® group. Saline group is analyzed separately.

Mean change from baseline to 3 weeks in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=150 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Evaluator Global Assessment Comparing Cingal® to Monovisc® (ITT)	-37.5 score on a scale Standard Deviation 21.0	-32.6 score on a scale Standard Deviation 21.3	—

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

Mean change from baseline to 26 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (ITT population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=69 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Patient Global Assessment (PGA) Comparing Cingal® to Saline (ITT)	-37.0 score on a scale Standard Error 1.5	-26.3 score on a scale Standard Error 2.5	—

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

Mean change from baseline to 26 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=149 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=69 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Evaluator Global Assessment Comparing Cingal® to Saline (ITT)	-37.8 score on a scale Standard Error 1.5	-28.7 score on a scale Standard Error 2.8	—

SECONDARY outcome

Timeframe: 1 Week

Population: Per Protocol (PP) Population to compare Cingal® group to Monovisc® group. Saline group is analyzed separately.

Mean change in knee pain from baseline to 1 week as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (PP population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=136 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=135 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (PP)	-35.7 score on a scale Standard Deviation 20.3	-29.2 score on a scale Standard Deviation 21.7	—

SECONDARY outcome

Timeframe: 3 Weeks

Population: Per Protocol (PP) Population to compare Cingal® group to Monovisc® group. Saline group is analyzed separately.

Mean change in knee pain from baseline to 3 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (PP population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=137 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=135 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (PP)	-41.3 score on a scale Standard Deviation 19.2	-35.3 score on a scale Standard Deviation 22.0	—

SECONDARY outcome

Timeframe: 12 Weeks

Population: Per Protocol (PP) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

The post treatment Responder Rate comparing Cingal® and Saline at 12 weeks is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index (PP population). The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder. The criteria for response are (1) improvement in pain or physical function ≥50% and an absolute change ≥20 mm; or (2) improvement of ≥20% with an absolute change ≥10 mm in at least two of the following three categories: pain, physical function, and patient's global assessment.

A higher percentage of subjects responding indicates a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=137 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=63 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
OMERACT-OARSI Responder Index Comparing Cingal® to Saline (PP)	92.8 percentage of subjects	83.6 percentage of subjects	—

SECONDARY outcome

Timeframe: 12 Weeks

Population: Per Protocol (PP) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

Mean change from baseline to 12 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (PP population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=137 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=63 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Patient Global Assessment (PGA) Comparing Cingal® to Saline (PP)	-37.8 score on a scale Standard Error 1.5	-26.0 score on a scale Standard Error 2.6	—

SECONDARY outcome

Timeframe: 1 Week

Population: Per Protocol (PP) Population to compare Cingal® group to Monovisc® group. Saline group is analyzed separately.

The post treatment Responder Rate comparing Cingal® and Monovisc® at 1 week is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index (PP population). The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder. A higher percentage of subjects responding indicates a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=136 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=135 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (PP)	-33.7 score on a scale Standard Deviation 22.3	-27.1 score on a scale Standard Deviation 22.2	—

SECONDARY outcome

Timeframe: 3 Weeks

Population: Per Protocol (PP) Population to compare Cingal® group to Monovisc® group. Saline group is analyzed separately.

Mean change from baseline to 3 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Monovisc® arms (PP population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=137 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=135 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (PP)	-39.2 score on a scale Standard Deviation 20.9	-32.4 score on a scale Standard Deviation 22.7	—

SECONDARY outcome

Timeframe: 26 Weeks

Population: Per Protocol (PP) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

Mean change in knee pain from baseline to 26 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group (PP population). The WOMAC Pain Score is a validated 100mm visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=134 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=62 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline. (PP)	-41.2 score on a scale Standard Error 1.4	-32.4 score on a scale Standard Error 2.3	—

SECONDARY outcome

Timeframe: 12 Weeks

Population: Per Protocol (PP) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

Mean change from baseline to 12 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=137 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=63 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Evaluator Global Assessment Comparing Cingal® to Saline (PP)	-37.7 score on a scale Standard Error 1.5	-28.4 score on a scale Standard Error 2.9	—

SECONDARY outcome

Timeframe: 1 Week

Population: Per Protocol (PP) Population to compare Cingal® group to Monovisc® group. Saline group is analyzed separately.

Mean change from baseline to 1 week in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=136 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=135 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Evaluator Global Assessment Comparing Cingal® and Monovisc® (PP).	-32.9 score on a scale Standard Deviation 19.2	-26.5 score on a scale Standard Deviation 19.2	—

SECONDARY outcome

Timeframe: 3 Week

Population: Per Protocol (PP) Population to compare Cingal® group to Monovisc® group. Saline group is analyzed separately.

Mean change from baseline to 3 weeks in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=137 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=135 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Evaluator Global Assessment Comparing Cingal® to Monovisc® (PP)	-38.6 score on a scale Standard Deviation 20.4	-32.0 score on a scale Standard Deviation 20.9	—

SECONDARY outcome

Timeframe: 26 Weeks

Population: Per Protocol (PP) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

Mean change from baseline to 26 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (PP population). The PGA is completed by the subject answering the question "Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today?" The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=134 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=62 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Patient Global Assessment (PGA) Comparing Cingal® to Saline (PP)	-38.6 score on a scale Standard Error 1.6	-27.0 score on a scale Standard Error 2.7	—

SECONDARY outcome

Timeframe: 26 Weeks

Population: Per Protocol (PP) Population to compare Cingal® group to Saline group. Monovisc® group is analyzed separately.

Mean change from baseline to 26 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question "Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today?" The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome.

Outcome measures

Measure	Hyaluronic Acid and TH (Cingal®) n=134 Participants Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=62 Participants Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Evaluator Global Assessment Comparing Cingal® to Saline (PP)	-39.1 score on a scale Standard Error 1.5	-29.8 score on a scale Standard Error 2.9	—

Adverse Events

Hyaluronic Acid and TH (Cingal®)

Serious events: 2 serious events

Other events: 36 other events

Deaths: 0 deaths

Hyaluronic Acid (Monovisc®)

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Saline

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Hyaluronic Acid and TH (Cingal®) n=149 participants at risk Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=150 participants at risk Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline n=69 participants at risk Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Endocrine disorders Benign Neoplasm of Adrenal Gland	0.67% 1/149 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/69 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Musculoskeletal and connective tissue disorders Herniated Disc	0.67% 1/149 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/69 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Musculoskeletal and connective tissue disorders Post-Laminectomy Syndrome	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Psychiatric disorders Mania Disorder	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Nervous system disorders Peripheral Facial Nerve Damage	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions

Other adverse events

Measure	Hyaluronic Acid and TH (Cingal®) n=149 participants at risk Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid and TH	Hyaluronic Acid (Monovisc®) n=150 participants at risk Single injection of sodium hyaluronate supplied as a 4 mL unit dose in a 5 mL glass syringe Hyaluronic Acid	Saline n=69 participants at risk Single injection of 0.9% saline supplied as a 4 mL unit dose in a 5mL glass syringe Saline: Saline placebo packaged to look identical to comparator syringes.
Cardiac disorders Palpitations	1.3% 2/149 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/69 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Gastrointestinal disorders Abdominal distension	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Gastrointestinal disorders Abdominal pain upper	2.0% 3/149 • Number of events 3 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.67% 1/150 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/69 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Gastrointestinal disorders Toothache	1.3% 2/149 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.67% 1/150 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
General disorders Oedema peripheral	1.3% 2/149 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/69 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Infections and infestations Bronchitis	1.3% 2/149 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.67% 1/150 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/69 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Infections and infestations Gastroenteritis viral	0.67% 1/149 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Infections and infestations Influenza	2.0% 3/149 • Number of events 3 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.3% 2/150 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Infections and infestations Nasopharyngitis	3.4% 5/149 • Number of events 5 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	2.7% 4/150 • Number of events 4 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	2.9% 2/69 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Infections and infestations Viral infection	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	2.0% 3/150 • Number of events 3 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/69 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Injury, poisoning and procedural complications Post laminectomy syndrome	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Musculoskeletal and connective tissue disorders Arthralgia	2.7% 4/149 • Number of events 4 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	4.7% 7/150 • Number of events 7 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Musculoskeletal and connective tissue disorders Back pain	1.3% 2/149 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	2.0% 3/150 • Number of events 3 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Musculoskeletal and connective tissue disorders Joint stiffness	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.3% 2/150 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/69 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.67% 1/149 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	2.0% 3/150 • Number of events 3 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Musculoskeletal and connective tissue disorders Spinal Pain	0.67% 1/149 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.67% 1/150 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	2.9% 2/69 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Nervous system disorders Headache	5.4% 8/149 • Number of events 8 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	5.3% 8/150 • Number of events 8 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	2.9% 2/69 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Nervous system disorders Migrane	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Nervous system disorders Parkinsonism	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Nervous system disorders VIIth nerve injury	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Psychiatric disorders Mania	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Psychiatric disorders Nervousness	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.3% 2/150 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.67% 1/149 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	2.9% 2/69 • Number of events 2 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Skin and subcutaneous tissue disorders Erythema	0.67% 1/149 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.67% 1/150 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Surgical and medical procedures Tooth extraction	0.00% 0/149 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.00% 0/150 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions
Vascular disorders Hypertension	0.67% 1/149 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	0.67% 1/150 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions	1.4% 1/69 • Number of events 1 • Adverse Event data was collected at baseline, and at 1, 3, 6, 12, 18 and 26 week follow-up visits. Definitions used are in accordance with clinicaltrials.gov definitions

Additional Information

Carol Pekar, VP Clinical Affairs

Anika Therapeutics, Inc.

Phone: 781.457.9218

Email: cpekar@anikatherapeutics.com

Results disclosure agreements

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