Trial Outcomes & Findings for Study to Compare Exposure of TA Following Administration of FX006 or TAcs in Patients With OA of the Shoulder or Hip (NCT NCT03382262)

Last Updated: 2024-01-24

Results Overview

Characterize the Pharmacokinetic Profile of FX006 and TCA IR \[Time Frame: Day 1 (pre-treatment,1, 2, 3, 4, 5, 6, 8,10, and 12 hrs. post-dose) and Days 2, 3, 5, 8, 15, 22, 29, 57,and 85\] For the PK analysis and individual concentration vs. time plots, a concentration that is BLOQ is assigned a value of zero if it occurs in a profile before the first measurable concentration. If a BLOQ value occurs after a measurable concentration in a profile and is followed by a value above the lower limit of quantification, then the BLOQ is treated as missing data. If a BLOQ value occurs at the end of the collection interval (after the last quantifiable concentration) it is set to zero. If two BLOQ values occur in succession after Cmax, the profile is deemed to have terminated at the first BLOQ value and any subsequent concentrations are set to zero for PK calculations

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

55 participants

Primary outcome timeframe

12 Weeks

Results posted on

2024-01-24

Participant Flow

The recruitment period for this study was from December 2017 to July 2018. The patients were enrolled at medical clinics.

Participant milestones

Participant milestones
Measure	FX006 32 mg Shoulder Single intra-articular (IA) injection of FX006 32 mg FX006 32 mg: Extended-release 32 mg FX006 IA injection in the Shoulder	TAcs 40 mg Shoulder Single intra-articular (IA) injection of TAcs 40 mg TAcs 40 mg: Immediate-release 40mg TAcs IA injection in the Shoulder	FX006 32 mg Hip Single intra-articular (IA) injection of FX006 32 mg FX006 32 mg: Extended-release 32 mg FX006 IA injection in the Hip	TAcs 40 mg Hip Single intra-articular (IA) injection of TAcs 40 mg TAcs 40 mg: Immediate-release 40mg TAcs IA injection in the Hip
Overall Study STARTED	12	13	15	15
Overall Study COMPLETED	12	13	14	14
Overall Study NOT COMPLETED	0	0	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	FX006 32 mg Shoulder Single intra-articular (IA) injection of FX006 32 mg FX006 32 mg: Extended-release 32 mg FX006 IA injection in the Shoulder	TAcs 40 mg Shoulder Single intra-articular (IA) injection of TAcs 40 mg TAcs 40 mg: Immediate-release 40mg TAcs IA injection in the Shoulder	FX006 32 mg Hip Single intra-articular (IA) injection of FX006 32 mg FX006 32 mg: Extended-release 32 mg FX006 IA injection in the Hip	TAcs 40 mg Hip Single intra-articular (IA) injection of TAcs 40 mg TAcs 40 mg: Immediate-release 40mg TAcs IA injection in the Hip
Overall Study Physician Decision	0	0	1	0
Overall Study Withdrawal by Subject	0	0	0	1

Baseline Characteristics

Study to Compare Exposure of TA Following Administration of FX006 or TAcs in Patients With OA of the Shoulder or Hip

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FX006 32 mg Shoulder n=12 Participants Single intra-articular (IA) injection of FX006 32 mg in the Shoulder FX006 32 mg: Extended-release 32 mg FX006 IA injection	TAcs 40 mg Shoulder n=13 Participants Single intra-articular (IA) injection of TAcs 40 mg in the Shoulder TAcs 40 mg: Immediate-release 40mg TAcs IA injection	FX006 32 mg Hip n=15 Participants Single intra-articular (IA) injection of FX006 32 mg in the Hip FX006 32 mg: Extended-release 32 mg FX006 IA injection	TAcs 40 mg Hip n=15 Participants Single intra-articular (IA) injection of TAcs 40 mg in the Hip TAcs 40 mg: Immediate-release 40mg TAcs IA injection	Total n=55 Participants Total of all reporting groups
Age, Continuous	63.2 years STANDARD_DEVIATION 11.39 • n=5 Participants	61.9 years STANDARD_DEVIATION 8.10 • n=7 Participants	58.1 years STANDARD_DEVIATION 7.60 • n=5 Participants	60.1 years STANDARD_DEVIATION 7.09 • n=4 Participants	60.7 years STANDARD_DEVIATION 8.53 • n=21 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	5 Participants n=4 Participants	28 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	10 Participants n=4 Participants	27 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	13 Participants n=7 Participants	14 Participants n=5 Participants	14 Participants n=4 Participants	50 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	13 Participants n=21 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	9 Participants n=4 Participants	38 Participants n=21 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	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	12 participants n=5 Participants	13 participants n=7 Participants	15 participants n=5 Participants	15 participants n=4 Participants	55 participants n=21 Participants
Body Mass Index (BMI)	28.9 kg/mg^2 STANDARD_DEVIATION 5.98 • n=5 Participants	30.7 kg/mg^2 STANDARD_DEVIATION 3.59 • n=7 Participants	29.3 kg/mg^2 STANDARD_DEVIATION 3.49 • n=5 Participants	31.0 kg/mg^2 STANDARD_DEVIATION 4.40 • n=4 Participants	30.01 kg/mg^2 STANDARD_DEVIATION 4.367 • n=21 Participants

PRIMARY outcome

Timeframe: 12 Weeks

Population: All patients in the Safety population who received study drug, completed scheduled sampling and had sufficient plasma concentration data. 50 of 55 patients were included. Four unique patients for whom hip was the index joint were excluded due to IP administration deviations. One of the four was also found to be enrolled at 2 separate study centers.

Outcome measures

Outcome measures
Measure	FX006 32 mg Shoulder n=12 Participants Single intra-articular (IA) injection of FX006 32 mg in the Shoulder FX006 32 mg: Extended-release 32 mg FX006 IA injection	TAcs 40 mg Shoulder n=13 Participants Single intra-articular (IA) injection of TAcs 40 mg in the Shoulder TAcs 40 mg: Immediate-release 40mg TAcs IA injection	FX006 32 mg Hip n=11 Participants Single intra-articular (IA) injection of FX006 32 mg in the Hip FX006 32 mg: Extended-release 32 mg FX006 IA injection	TAcs 40 mg Hip n=14 Participants Single intra-articular (IA) injection of TAcs 40 mg in the Hip TAcs 40 mg: Immediate-release 40mg TAcs IA injection
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day 1 - Hour 1	1061.8 pg/mL Interval 819.95 to 1375.09	1104.1 pg/mL Interval 578.17 to 2108.52	681.8 pg/mL Interval 334.47 to 1389.69	3862.3 pg/mL Interval 2024.11 to 7370.02
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day 1 - Hour 2	1117.6 pg/mL Interval 838.98 to 1488.62	1344.8 pg/mL Interval 682.4 to 2650.05	752.2 pg/mL Interval 364.55 to 1551.9	4052.4 pg/mL Interval 2134.61 to 7693.33
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day 1 - Hour 3	1140.0 pg/mL Interval 849.77 to 1529.44	1501.8 pg/mL Interval 774.05 to 2913.69	748.0 pg/mL Interval 349.37 to 1601.44	4519.3 pg/mL Interval 2286.88 to 8930.88
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day 1 - Hour 4	1142.4 pg/mL Interval 822.55 to 1586.49	1594.1 pg/mL Interval 856.43 to 2967.05	776.1 pg/mL Interval 352.73 to 1707.82	4557.8 pg/mL Interval 2362.49 to 8793.0
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day 1 - Hour 5	1093.8 pg/mL Interval 759.94 to 1574.4	1662.7 pg/mL Interval 861.73 to 3208.09	792.9 pg/mL Interval 360.39 to 1744.51	4672.6 pg/mL Interval 2429.24 to 8987.65
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day 1 - Hour 6	1052.8 pg/mL Interval 729.94 to 1518.37	1689.6 pg/mL Interval 893.53 to 3194.85	743.5 pg/mL Interval 331.07 to 1669.73	4469.8 pg/mL Interval 2393.87 to 8346.03
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day 1 - Hour 8	1016.2 pg/mL Interval 702.66 to 1469.64	1668.3 pg/mL Interval 887.88 to 3134.86	705.0 pg/mL Interval 307.07 to 1618.77	4102.3 pg/mL Interval 2232.93 to 7536.76
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day 1 - Hour 10	951.4 pg/mL Interval 670.78 to 1349.34	1506.3 pg/mL Interval 819.27 to 2769.61	698.2 pg/mL Interval 307.74 to 1583.97	3615.6 pg/mL Interval 2033.96 to 6427.3
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day 1 - Hour 12	903.8 pg/mL Interval 637.58 to 1281.1	1531.3 pg/mL Interval 806.98 to 2905.65	675.1 pg/mL Interval 296.0 to 1539.62	3276.2 pg/mL Interval 1858.64 to 5775.0
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day 2 - Hour 24	943.4 pg/mL Interval 690.74 to 1288.35	1467.0 pg/mL Interval 884.1 to 2434.35	791.0 pg/mL Interval 340.46 to 1837.6	3218.8 pg/mL Interval 1965.24 to 5272.05
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day - 3	903.4 pg/mL Interval 639.75 to 1275.69	1413.1 pg/mL Interval 856.25 to 2332.05	682.1 pg/mL Interval 292.51 to 1590.6	1723.6 pg/mL Interval 1218.72 to 2437.7
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day - 5	754.6 pg/mL Interval 536.22 to 1061.93	1038.2 pg/mL Interval 724.11 to 1488.44	562.4 pg/mL Interval 242.23 to 1305.93	897.3 pg/mL Interval 644.77 to 1248.66
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day - 8	678.1 pg/mL Interval 497.82 to 923.66	857.8 pg/mL Interval 596.48 to 1233.52	472.3 pg/mL Interval 202.04 to 1103.9	525.3 pg/mL Interval 296.03 to 932.01
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day - 15	397.6 pg/mL Interval 287.43 to 549.88	722.7 pg/mL Interval 574.45 to 909.25	382.6 pg/mL Interval 270.89 to 540.52	444.7 pg/mL Interval 278.24 to 710.85
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day - 22	268.3 pg/mL Interval 186.53 to 385.82	476.7 pg/mL Interval 333.94 to 680.44	235.0 pg/mL Interval 170.8 to 323.29	331.6 pg/mL Interval 214.93 to 511.48
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day - 29	201.0 pg/mL Interval 134.57 to 300.21	418.7 pg/mL Interval 300.39 to 583.66	256.3 pg/mL Interval 173.31 to 379.15	281.8 pg/mL Interval 179.32 to 442.91
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day - 57	151.8 pg/mL Interval 92.6 to 248.73	200 pg/mL Interval 140.83 to 284.08	225.1 pg/mL Interval 156.31 to 324.15	133.1 pg/mL Interval 74.28 to 238.5
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma Day - 85	100.1 pg/mL Interval 54.22 to 184.86	131.4 pg/mL Interval 64.14 to 269.25	112.0 pg/mL Interval 58.14 to 215.61	92.5 pg/mL Interval 51.16 to 167.11

PRIMARY outcome

Timeframe: 12 Weeks

Population: All patients randomized to receive either FX006 or TAcs in the hip or shoulder.

Analyses of adverse events (AE) were performed for events considered treatment-emergent (TE). TE was defined as any AE with onset after administration of the 1st dose of study drug or any event present at baseline but worsened in intensity through the study. Severity was graded by the PI using the Common Terminology Criteria for AEs Version 4.0. Grading went from Grade 1 (Mild) to Grade 5 (Death Related to AE).

Outcome measures

Outcome measures
Measure	FX006 32 mg Shoulder n=12 Participants Single intra-articular (IA) injection of FX006 32 mg in the Shoulder FX006 32 mg: Extended-release 32 mg FX006 IA injection	TAcs 40 mg Shoulder n=13 Participants Single intra-articular (IA) injection of TAcs 40 mg in the Shoulder TAcs 40 mg: Immediate-release 40mg TAcs IA injection	FX006 32 mg Hip n=15 Participants Single intra-articular (IA) injection of FX006 32 mg in the Hip FX006 32 mg: Extended-release 32 mg FX006 IA injection	TAcs 40 mg Hip n=15 Participants Single intra-articular (IA) injection of TAcs 40 mg in the Hip TAcs 40 mg: Immediate-release 40mg TAcs IA injection
Total Number of Treatment Emergent Adverse Events	10 Events	7 Events	8 Events	17 Events

Adverse Events

FX006 32 mg Shoulder

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

TAcs 40 mg Shoulder

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

FX006 32 mg Hip

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

TAcs 40 mg Hip

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Scott Kelley MD, Chief Medical Officer

Flexion Therapeutics

Phone: 781-305-7142

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	FX006 32 mg Shoulder n=12 participants at risk Single intra-articular (IA) injection of FX006 32 mg in the Shoulder FX006 32 mg: Extended-release 32 mg FX006 IA injection	TAcs 40 mg Shoulder n=13 participants at risk Single intra-articular (IA) injection of TAcs 40 mg in the Shoulder TAcs 40 mg: Immediate-release 40mg TAcs IA injection	FX006 32 mg Hip n=15 participants at risk Single intra-articular (IA) injection of FX006 32 mg in the Hip FX006 32 mg: Extended-release 32 mg FX006 IA injection	TAcs 40 mg Hip n=15 participants at risk Single intra-articular (IA) injection of TAcs 40 mg in the Hip TAcs 40 mg: Immediate-release 40mg TAcs IA injection
Ear and labyrinth disorders Ear Pain	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	7.7% 1/13 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Gastrointestinal disorders Nausea	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	7.7% 1/13 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
General disorders Influenza Like Illness	8.3% 1/12 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
General disorders Injection Site Hypoaesthesia	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Infections and infestations Nasopharyngitis	16.7% 2/12 • Number of events 2 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Infections and infestations Upper Respiratory Tract Infection	8.3% 1/12 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Infections and infestations Urinary Tract Infection	8.3% 1/12 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Infections and infestations Viral Upper Respiratory Tract Infection	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Injury, poisoning and procedural complications Contusion	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Injury, poisoning and procedural complications Fall	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Injury, poisoning and procedural complications Incision Site Pain	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Injury, poisoning and procedural complications Periorbital Haemorrhage	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Injury, poisoning and procedural complications Road Traffic Accident	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Injury, poisoning and procedural complications Skin Abrasion	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 2 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Investigations Blood Pressure Increased	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Metabolism and nutrition disorders Gout	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	13.3% 2/15 • Number of events 2 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Musculoskeletal and connective tissue disorders Joint Range of Motion Decreased	8.3% 1/12 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	7.7% 1/13 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal Discomfort	8.3% 1/12 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	7.7% 1/13 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	7.7% 1/13 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Musculoskeletal and connective tissue disorders Pain In Extremity	8.3% 1/12 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Nervous system disorders Headache	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Nervous system disorders Hypoaesthesia	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Reproductive system and breast disorders Testicular Pain	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	6.7% 1/15 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	7.7% 1/13 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Respiratory, thoracic and mediastinal disorders Respiratory Tract Congestion	8.3% 1/12 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Skin and subcutaneous tissue disorders Melanocytic Hypoplasia	8.3% 1/12 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/13 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.
Vascular disorders Hot Flush	0.00% 0/12 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	7.7% 1/13 • Number of events 1 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.	0.00% 0/15 • Adverse events were collected following IA administration through the final study visit at 12 weeks.