Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of Topically Applied TV-45070 (Ointment) in Participants With Primary Osteoarthritis (OA) Affecting a Single Knee (NCT NCT02068599)
NCT ID: NCT02068599
Last Updated: 2021-11-09
Results Overview
The Western Ontario and McMasters Universities Arthritis Index \[WOMAC\] is a widely used, validated, patient-reported questionnaire used to assess pain, stiffness, and physical function in patients with OA of the knee. It consists of 24 items separated into 3 domains (pain \[5 items\], stiffness \[2 items\], and physical function \[17 items\]). WOMAC Question 1 is the first question in the pain domain and asks patients to rate their pain in the target knee while walking on a flat surface. The possible score for each item ranges from 0 (no pain) to 100 mm (worst pain). Participants record their response to WOMAC Question 1 in the study diary based on average pain upon walking since the last assessment or over the past 12 hours. Negative change from baseline scores indicate improvement in pain. MMRM includes week, treatment, study center, and treatment by week interaction as fixed factors; baseline average evening WOMAC Question 1 score as a covariate; and patient as a random factor.
COMPLETED
PHASE2
389 participants
Baseline (day -5 to day -1), Last 5 days of treatment (day 24 to day 28)
2021-11-09
Participant Flow
978 patients with primary OA of the knee were screened for enrollment into this study. 389 patients at 41 centers in the US met entry criteria. Of the 589 patients not enrolled, 551 were excluded on the basis of inclusion/exclusion criteria, 25 patients withdrew consent, and 8 patients were lost to follow-up before the baseline visit.
After stratification by R1150W polymorphism status: - homozygous minor allele (positive, AA), - heterozygous (positive, AG), and - homozygous common allele (negative, GG), participants were randomly assigned by interactive response technology (IRT) to receive treatment in 1 of 3 treatment groups in a 1:1:1 ratio.
Participant milestones
| Measure |
TV-45070 4%
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Overall Study
STARTED
|
130
|
129
|
130
|
|
Overall Study
Safety Analysis Set
|
129
|
128
|
130
|
|
Overall Study
Full Analysis Set
|
129
|
128
|
130
|
|
Overall Study
COMPLETED
|
119
|
119
|
117
|
|
Overall Study
NOT COMPLETED
|
11
|
10
|
13
|
Reasons for withdrawal
| Measure |
TV-45070 4%
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
4
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
7
|
5
|
|
Overall Study
Protocol Violation
|
4
|
2
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
3
|
|
Overall Study
Noncompliance
|
0
|
0
|
1
|
Baseline Characteristics
A Study to Evaluate the Safety and Efficacy of Topically Applied TV-45070 (Ointment) in Participants With Primary Osteoarthritis (OA) Affecting a Single Knee
Baseline characteristics by cohort
| Measure |
TV-45070 4%
n=130 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=129 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=130 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Total
n=389 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
60.2 years
STANDARD_DEVIATION 9.17 • n=5 Participants
|
59.2 years
STANDARD_DEVIATION 9.52 • n=7 Participants
|
59.0 years
STANDARD_DEVIATION 9.65 • n=5 Participants
|
59.5 years
STANDARD_DEVIATION 9.44 • n=4 Participants
|
|
Sex: Female, Male
Female
|
71 Participants
n=5 Participants
|
75 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
228 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
59 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
161 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
20 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
74 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
110 Participants
n=5 Participants
|
104 Participants
n=7 Participants
|
101 Participants
n=5 Participants
|
315 Participants
n=4 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
|
|
Race
White
|
88 Participants
n=5 Participants
|
83 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
259 Participants
n=4 Participants
|
|
Race
Black
|
25 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
91 Participants
n=4 Participants
|
|
Race
Asian
|
14 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
|
Race
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race
Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race
Other
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
R1150W Polymorphism Status
Homozygous minor allele (positive, AA)
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
R1150W Polymorphism Status
Heterozygous (positive, AG)
|
27 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
81 Participants
n=4 Participants
|
|
R1150W Polymorphism Status
Homozygous common allele (negative, GG)
|
101 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
103 Participants
n=5 Participants
|
302 Participants
n=4 Participants
|
|
Weight
|
79.83 kg
STANDARD_DEVIATION 14.119 • n=5 Participants
|
80.87 kg
STANDARD_DEVIATION 13.010 • n=7 Participants
|
80.29 kg
STANDARD_DEVIATION 13.633 • n=5 Participants
|
80.33 kg
STANDARD_DEVIATION 13.568 • n=4 Participants
|
|
Height
|
168.41 cm
STANDARD_DEVIATION 10.835 • n=5 Participants
|
169.06 cm
STANDARD_DEVIATION 9.927 • n=7 Participants
|
167.99 cm
STANDARD_DEVIATION 9.526 • n=5 Participants
|
168.48 cm
STANDARD_DEVIATION 10.095 • n=4 Participants
|
|
Body Mass Index
|
27.992 kg/m^2
STANDARD_DEVIATION 3.0800 • n=5 Participants
|
28.190 kg/m^2
STANDARD_DEVIATION 3.0207 • n=7 Participants
|
28.340 kg/m^2
STANDARD_DEVIATION 3.2364 • n=5 Participants
|
28.174 kg/m^2
STANDARD_DEVIATION 3.1092 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline (day -5 to day -1), Last 5 days of treatment (day 24 to day 28)Population: The full analysis set (FAS) include all patients in the intent to treat (ITT) population who receive at least 1 dose of study drug and have at least 1 post baseline efficacy assessment. Both baseline and treatment values must be available for a participant to be included.
The Western Ontario and McMasters Universities Arthritis Index \[WOMAC\] is a widely used, validated, patient-reported questionnaire used to assess pain, stiffness, and physical function in patients with OA of the knee. It consists of 24 items separated into 3 domains (pain \[5 items\], stiffness \[2 items\], and physical function \[17 items\]). WOMAC Question 1 is the first question in the pain domain and asks patients to rate their pain in the target knee while walking on a flat surface. The possible score for each item ranges from 0 (no pain) to 100 mm (worst pain). Participants record their response to WOMAC Question 1 in the study diary based on average pain upon walking since the last assessment or over the past 12 hours. Negative change from baseline scores indicate improvement in pain. MMRM includes week, treatment, study center, and treatment by week interaction as fixed factors; baseline average evening WOMAC Question 1 score as a covariate; and patient as a random factor.
Outcome measures
| Measure |
TV-45070 4%
n=121 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=123 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=120 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Change From Baseline to Last 5 Days of Treatment in the Average Evening Pain Intensity In the Target Knee When Walking on a Flat Surface Using a Mixed Model for Repeated Measures (MMRM)
|
-20.56 units on a scale
Standard Error 1.937
|
-23.08 units on a scale
Standard Error 1.923
|
-24.82 units on a scale
Standard Error 1.928
|
SECONDARY outcome
Timeframe: Baseline (day -5 to day -1), Last 5 days of treatment (day 24 to day 28)Population: Full analysis set. Both baseline and treatment values must be available for a participant to be included. For pain subscale, if more than 1 item is missing, the subscale total will not be calculated; otherwise the missing value will be replaced by average of the non-missing values in the subscale.
The five items in the WOMAC Pain Subscale cover pain during walking, using stairs, in bed, sitting or lying, and standing. Daily WOMAC pain subscale score is calculated as the sum of the 5-item pain subscale scores (WOMAC) recorded at evening for a total range of 0 (no pain) to 500 (worst pain on all 5 items). Negative change from baseline scores indicate improvement in pain. MMRM includes week, treatment, study center, and treatment by week interaction as fixed factors; baseline average evening WOMAC scores for the 5-item pain subscale as a covariate; and patient as a random factor.
Outcome measures
| Measure |
TV-45070 4%
n=121 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=123 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=120 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Change From Baseline to Last 5 Days of Treatment in the Average Daily WOMAC Pain Subscale Score In the Target Knee Using a Mixed Model for Repeated Measures
|
-99.67 units on a scale
Standard Error 9.365
|
-108.52 units on a scale
Standard Error 9.300
|
-117.53 units on a scale
Standard Error 9.329
|
SECONDARY outcome
Timeframe: Baseline (day -5 to day -1), Last 5 days of treatment (day 24 to day 28)Population: The full analysis set (FAS) include all patients in the intent to treat (ITT) population who receive at least 1 dose of study drug and have at least 1 post baseline efficacy assessment. Both baseline and treatment values must be available for a participant to be included.
The Western Ontario and McMasters Universities Arthritis Index \[WOMAC\] is a widely used, validated, patient-reported questionnaire used to assess pain, stiffness, and physical function in patients with OA of the knee. It consists of 24 items separated into 3 domains (pain \[5 items\], stiffness \[2 items\], and physical function \[17 items\]). The possible score for each item ranges from 0 (no pain) to 100 mm (worst pain). WOMAC Question 1 is the first question in the pain domain and asks patients to rate their pain in the target knee while walking on a flat surface. Participants record their response to WOMAC Question 1 in the study diary based on average pain upon walking since the last assessment or over the past 12 hours. Negative change from baseline scores indicate improvement in pain. MMRM includes week, treatment, study center, and treatment by week interaction as fixed factors; baseline average morning WOMAC Question 1 score as a covariate; and patient as a random factor.
Outcome measures
| Measure |
TV-45070 4%
n=121 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=122 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=120 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Change From Baseline to Last 5 Days of Treatment in the Average Morning Pain Intensity In the Target Knee When Walking on a Flat Surface Using a Mixed Model for Repeated Measures (MMRM)
|
-19.84 units on a scale
Standard Error 1.968
|
-21.39 units on a scale
Standard Error 1.955
|
-23.45 units on a scale
Standard Error 1.956
|
SECONDARY outcome
Timeframe: Baseline (day 1, predose), Treatment: Week 4 (day 29)Population: Full analysis set. Both baseline and treatment values must be available for a participant to be included. For physical function subscale, if more than 3 items are missing the subscale total will not be calculated; otherwise the missing value will be replaced by the average of the non-missing values in the subscale.
The seventeen items in the WOMAC physical function subscale cover stair use, rising from sitting, standing, bending, walking, getting in / out of a car, shopping, putting on / taking off socks, rising from bed, lying in bed, getting in / out of bath, sitting, getting on / off toilet, heavy household duties, light household duties. WOMAC physical function subscale score is calculated as the sum of the 17-item physical function subscale scores (WOMAC) for a total range of 0 (no pain) to 1700 (worst pain on all 17 items). Negative change from baseline scores indicate improvement in pain. MMRM includes week, treatment, study center, and treatment by week interaction as fixed factors; baseline physical function WOMAC scores for the 17-item subscale as a covariate; and patient as a random factor.
Outcome measures
| Measure |
TV-45070 4%
n=120 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=121 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=118 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Change From Baseline (Randomization Visit) to the Week 4 Visit in the WOMAC Physical Function Subscale Score for the Target Knee Using a Mixed Model for Repeated Measures
|
-372.88 units on a scale
Standard Error 35.169
|
-446.79 units on a scale
Standard Error 34.812
|
-396.39 units on a scale
Standard Error 35.590
|
SECONDARY outcome
Timeframe: Baseline (day 1, predose), Treatment: Week 4 (day 29)Population: Full analysis set. Both baseline and treatment values must be available for a participant to be included. For stiffness subscale, if both items are missing, the subscale total will not be calculated; otherwise the missing value will be replaced with the non-missing one in the subscale.
The two items in the WOMAC stiffness subscale cover stiffness after first waking and later in the day. WOMAC stiffness subscale score is calculated as the sum of the 2-item stiffness subscale scores (WOMAC) for a total range of 0 (no stiffness) to 200 (worst stiffness on both items). Negative change from baseline scores indicate improvement in stiffness. MMRM includes week, treatment, study center, and treatment by week interaction as fixed factors; baseline stiffness WOMAC scores for the 2-item subscale as a covariate; and patient as a random factor.
Outcome measures
| Measure |
TV-45070 4%
n=120 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=121 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=118 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Change From Baseline (Randomization Visit) to the Week 4 Visit in the WOMAC Stiffness Subscale Score for the Target Knee Using a Mixed Model for Repeated Measures
|
-45.85 units on a scale
Standard Error 4.414
|
-52.49 units on a scale
Standard Error 4.358
|
-49.01 units on a scale
Standard Error 4.455
|
SECONDARY outcome
Timeframe: Baseline (day -5 to day -1), Last 5 days of treatment (day 24 to day 28)WOMAC Question 1 is the first question in the pain domain and asks patients to rate their pain in the target knee while walking on a flat surface. The possible score for each item ranges from 0 (no pain) to 100 mm (worst pain). Average pain is calculated using a MMRM which includes week, treatment, study center, and treatment by week interaction as fixed factors; baseline average evening WOMAC Question 1 score as a covariate; and patient as a random factor. Responder rate was calculated as 100 \* the value of (average WOMAC pain subscale during the last 5 days of treatment \[Days 24 to 28\]) - average WOMAC pain subscale at baseline \[the 5 days prior to randomization\])/average WOMAC pain subscale at baseline (the 5 days prior to randomization). Participants with missing responder rates were treated as nonresponders.
Outcome measures
| Measure |
TV-45070 4%
n=121 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=123 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=120 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Percentage of Participants With a >=30% and a >=50% Response in Average Evening Pain Intensity of WOMAC Question 1 in the Target Knee During the Last 5 Days of Treatment Compared With Baseline
>=50% responder rate
|
23.3 percentage of participants
|
33.6 percentage of participants
|
31.5 percentage of participants
|
|
Percentage of Participants With a >=30% and a >=50% Response in Average Evening Pain Intensity of WOMAC Question 1 in the Target Knee During the Last 5 Days of Treatment Compared With Baseline
<50% responder rate
|
70.5 percentage of participants
|
62.5 percentage of participants
|
60.8 percentage of participants
|
|
Percentage of Participants With a >=30% and a >=50% Response in Average Evening Pain Intensity of WOMAC Question 1 in the Target Knee During the Last 5 Days of Treatment Compared With Baseline
>=30% responder rate
|
45.0 percentage of participants
|
43.8 percentage of participants
|
46.9 percentage of participants
|
|
Percentage of Participants With a >=30% and a >=50% Response in Average Evening Pain Intensity of WOMAC Question 1 in the Target Knee During the Last 5 Days of Treatment Compared With Baseline
<30% responder rate
|
48.8 percentage of participants
|
52.3 percentage of participants
|
45.4 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline (day 1, predose), Treatment: Week 4 (day 29)Population: Full analysis set. If any of the 19 questions is missing, the PQAS-R total score will not be calculated for a given visit. If the entire questionnaire is not done at a scheduled time point, it will be considered missing and will not be imputed.
PQAS-R is a standardized self-report tool that measures various aspects of a participant's pain. There are 19 questions (question 19 has 2 parts) that ask the participant to rate the various aspects (intensity, sharpness, heat, cold, etc.) of his/her pain over the past week on average on a scale of 0 to 10 (0 = not \[aspect\] and 10 = the most or worst imaginable \[aspect\]). PQAS-R score at each visit is the sum of responses for the 19 questions for a total range of 0=no pain to 200=worst imaginable pain in all aspects. Negative change from baseline scores indicate improvement in stiffness. MMRM includes week, treatment, study center, and treatment by week interaction as fixed factors; baseline PQAS-R score for the 19 questions (20 parts) as a covariate; and patient as a random factor.
Outcome measures
| Measure |
TV-45070 4%
n=120 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=121 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=118 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Change From Baseline (Randomization Visit) to the Week 4 Visit in the Pain Quality Assessment Scale - Revised (PQAS-R) for the Target Knee Using a Mixed Model for Repeated Measures
|
-39.22 units on a scale
Standard Error 3.489
|
-40.65 units on a scale
Standard Error 3.453
|
-43.16 units on a scale
Standard Error 3.529
|
SECONDARY outcome
Timeframe: Weeks 2 (day 15), 4 (day 29)Population: Full analysis set of participants with data at the timepoint.
PGIC is a standardized self-report tool that measures the change in a participants overall status rating since the start of treatment on 7-point scale. The 7-point scale is defined as: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. The MMRM model includes week, treatment, study center, and treatment by week interaction as the fixed factors and unconstructed variance-covariance structure.
Outcome measures
| Measure |
TV-45070 4%
n=129 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=128 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=130 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Participants' Global Assess of Treatment as Measured by the Patient Global Impression of Change (PGIC) at Weeks 2 and 4 Using a Mixed Model for Repeated Measures (MMRM)
Week 2
|
2.87 units on a scale
Standard Error 0.086
|
2.90 units on a scale
Standard Error 0.086
|
2.86 units on a scale
Standard Error 0.088
|
|
Participants' Global Assess of Treatment as Measured by the Patient Global Impression of Change (PGIC) at Weeks 2 and 4 Using a Mixed Model for Repeated Measures (MMRM)
Week 4
|
2.81 units on a scale
Standard Error 0.096
|
2.66 units on a scale
Standard Error 0.095
|
2.60 units on a scale
Standard Error 0.097
|
SECONDARY outcome
Timeframe: Baseline (day 1, predose), Week 2 (day 15) and Week 4 (day 29)Population: Full analysis set of participants with data at the timepoints.
PGA is a simple self-report tool for measuring the overall way arthritis is affecting the patient at a particular point in time. There is 1 question and the response is provided on a visual analog scale (VAS) from 0 (very poor) to 100 (very good). The question is: Considering all the ways your arthritis affect you, how are you feeling today? Positive change from baseline scores indicate improvement. The MMRM model includes week, treatment, study center, and treatment by week interaction as the fixed factors; baseline PGA score as a covariate and unconstructed variance-covariance structure.
Outcome measures
| Measure |
TV-45070 4%
n=129 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=128 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=130 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Change From Baseline in the Patient Global Assessment (PGA) Scores at Weeks 2 and 4 Using a Mixed Model for Repeated Measures (MMRM)
Week 2
|
4.87 units on a scale
Standard Error 1.819
|
3.51 units on a scale
Standard Error 1.808
|
2.10 units on a scale
Standard Error 1.850
|
|
Change From Baseline in the Patient Global Assessment (PGA) Scores at Weeks 2 and 4 Using a Mixed Model for Repeated Measures (MMRM)
Week 4
|
5.44 units on a scale
Standard Error 1.949
|
6.35 units on a scale
Standard Error 1.935
|
4.62 units on a scale
Standard Error 1.973
|
SECONDARY outcome
Timeframe: Week 4 (day 29)Population: Full analysis set
Participants are classified as 'Yes' if the following criteria are met: - \>=50% improvement from baseline and an absolute change \>=20 on a scale of 1-100 in either the pain or physical function subscale (WOMAC). or 2 of the 3 criteria as below met: - 1) \>=20% improvement from baseline and an absolute change \>=10 on a scale of 1-100 in the pain subscale (WOMAC); - 2) \>=20% improvement from baseline and an absolute change \>=10 on a scale of 1-100 in the physical function subscale (WOMAC); - 3) at least a 20% improvement from baseline and an absolute change \>=10 on a scale of 1-100 in PGA. Otherwise, 'No' The responder rate per OMERACT-OARSI criteria was analyzed using a generalized estimating equation (GEE) method, where binary variable responder rate (Yes/No) was modeled through logit link function, with treatment, center, week, and treatment\*week as explanatory factors. The unstructured working correlation structure was applied.
Outcome measures
| Measure |
TV-45070 4%
n=129 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=128 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=130 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Percentage of Participants Who Are Responders Per Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Criteria at Week 4
Responder - Yes
|
47.3 percentage of participants
|
59.4 percentage of participants
|
51.5 percentage of participants
|
|
Percentage of Participants Who Are Responders Per Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Criteria at Week 4
Responder - No
|
46.5 percentage of participants
|
36.7 percentage of participants
|
40.8 percentage of participants
|
|
Percentage of Participants Who Are Responders Per Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Criteria at Week 4
Missing
|
6.2 percentage of participants
|
3.9 percentage of participants
|
7.7 percentage of participants
|
SECONDARY outcome
Timeframe: day 1 up to day 57Population: Safety analysis population. The safety population includes all randomized participants who receive at least one dose of study medication. In this population, treatment was assigned based upon the treatment participants actually receive regardless of the treatment to which they were randomized.
An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
Outcome measures
| Measure |
TV-45070 4%
n=129 Participants
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=128 Participants
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=130 Participants
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Participants With Treatment-Emergent Adverse Events
Serious TEAE
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Participants With Treatment-Emergent Adverse Events
Any treatment-emergent adverse event
|
43 Participants
|
37 Participants
|
47 Participants
|
|
Participants With Treatment-Emergent Adverse Events
Treatment-related TEAE
|
12 Participants
|
10 Participants
|
20 Participants
|
|
Participants With Treatment-Emergent Adverse Events
Death
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events
Withdrawn from treatment due to TEAE
|
3 Participants
|
2 Participants
|
2 Participants
|
Adverse Events
TV-45070 4%
TV-45070 8%
Placebo
Serious adverse events
| Measure |
TV-45070 4%
n=129 participants at risk
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=128 participants at risk
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=130 participants at risk
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.78%
1/129 • Number of events 1 • day 1 up to day 57
|
0.00%
0/128 • day 1 up to day 57
|
0.00%
0/130 • day 1 up to day 57
|
|
Infections and infestations
Influenza
|
0.00%
0/129 • day 1 up to day 57
|
0.00%
0/128 • day 1 up to day 57
|
0.77%
1/130 • Number of events 1 • day 1 up to day 57
|
Other adverse events
| Measure |
TV-45070 4%
n=129 participants at risk
TV-45070 ointment in a 4% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
TV-45070 8%
n=128 participants at risk
TV-45070 ointment in a 8% strength applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
Placebo
n=130 participants at risk
Placebo ointment applied topically twice daily to the target knee during the treatment period from day 1 through day 28.
|
|---|---|---|---|
|
General disorders
Application site exfoliation
|
4.7%
6/129 • Number of events 6 • day 1 up to day 57
|
4.7%
6/128 • Number of events 6 • day 1 up to day 57
|
6.9%
9/130 • Number of events 9 • day 1 up to day 57
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products, R&D Inc
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data
- Publication restrictions are in place
Restriction type: OTHER