Trial Outcomes & Findings for A Bioequivalence Study Using Clinical Endpoint for Diclofenac Sodium Gel 1% in Osteoarthritis Knee" (NCT NCT03172780)

Results Overview

Mean change in the total WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain subscale score for the target knee was compared to determine the superiority of the Test Drug and Reference Listed Drug (RLD) over placebo. Measure Description: Western Ontario and McMaster Universities Osteoarthritis Index WOMAC pain subscale score (pain score = min 0 to max 20), was determined by the sum of subject's responses to five questions (S1-S5) using a 5-point Likert scale (i.e., 'none'=0; 'mild'=1, 'moderate'=2; 'severe'=3; 'extreme'=4). Higher values represent worse outcome. 'How much pain do you have' when 'Walking on a flat surface' (S1), 'Going up or down stairs' (S2), 'at night while in bed' (S3), 'Sitting or lying' (S4), 'Standing upright' (S5)\]. The timepoints considered for the primary outcomes include baseline and week 4.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1220 participants

Primary outcome timeframe

4 weeks

Results posted on

2022-03-03

Participant Flow

Participant milestones

Participant milestones
Measure	Diclofenac Sodium Gel Diclofenac Sodium Gel, 1% Diclofenac sodium gel 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Voltaren® Gel Voltaren® Gel (Diclofenac Sodium Topical Gel) 1% Voltaren® Gel (Diclofenac Sodium Topical Gel) 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Placebo Gel Placebo gel Placebo gel: Vehicle Gel 4 gm, 4 times a day for 4 weeks
Overall Study STARTED	406	409	405
Overall Study COMPLETED	388	389	389
Overall Study NOT COMPLETED	18	20	16

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Bioequivalence Study Using Clinical Endpoint for Diclofenac Sodium Gel 1% in Osteoarthritis Knee"

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Diclofenac Sodium Gel n=406 Participants Diclofenac Sodium Gel, 1% Diclofenac sodium gel 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Voltaren® Gel n=409 Participants Voltaren® Gel (Diclofenac Sodium Topical Gel) 1% Voltaren® Gel (Diclofenac Sodium Topical Gel) 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Placebo Gel n=405 Participants Placebo gel Placebo gel: Vehicle Gel 4 gm, 4 times a day for 4 weeks	Total n=1220 Participants Total of all reporting groups
Age, Continuous	53.3 years STANDARD_DEVIATION 9.51 • n=5 Participants	53.4 years STANDARD_DEVIATION 9.40 • n=7 Participants	53.6 years STANDARD_DEVIATION 10.15 • n=5 Participants	53.4 years STANDARD_DEVIATION 9.68 • n=4 Participants
Sex: Female, Male Female	275 Participants n=5 Participants	288 Participants n=7 Participants	273 Participants n=5 Participants	836 Participants n=4 Participants
Sex: Female, Male Male	131 Participants n=5 Participants	121 Participants n=7 Participants	132 Participants n=5 Participants	384 Participants n=4 Participants
Race/Ethnicity, Customized Asian/Not Hispanic or Latino	406 Participants n=5 Participants	409 Participants n=7 Participants	405 Participants n=5 Participants	1220 Participants n=4 Participants
Region of Enrollment India	406 participants n=5 Participants	409 participants n=7 Participants	405 participants n=5 Participants	1220 participants n=4 Participants
WOMAC Pain subscale score for target knee	12.4 units on a scale STANDARD_DEVIATION 2.15 • n=5 Participants	12.5 units on a scale STANDARD_DEVIATION 2.16 • n=7 Participants	12.4 units on a scale STANDARD_DEVIATION 2.05 • n=5 Participants	12.4 units on a scale STANDARD_DEVIATION 2.12 • n=4 Participants

PRIMARY outcome

Timeframe: From baseline to week 4

Population: The PP Population was used for analysis of clinical equivalence between Mylan's Diclofenac gel and Voltaren gel. The primary outcome tested in this population was the equivalence of Mylan's Diclofenac sodium gel (1%) verses the Voltaren gel (1%) and thus only Diclofenac Sodium Gel and Voltaren Gel arms are present here. The placebo arm is presented for the superiority analysis.

Mean change in the total WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain subscale score for the target knee was compared to determine the clinical equivalence of Test Drug (Diclofenac sodium gel of 1% of Mylan Inc.) with the Reference Listed Drug (RLD) (Voltaren® Gel 1% of Novartis Consumer Health, Inc.) Measure Description: Western Ontario and McMaster Universities Osteoarthritis Index WOMAC pain subscale score (pain score = min 0 to max 20), was determined by the sum of subject's responses to five questions (S1-S5) using a 5-point Likert scale (i.e., 'none'=0; 'mild'=1, 'moderate'=2; 'severe'=3; 'extreme'=4). Higher values represent worse outcome. 'How much pain do you have' when 'Walking on a flat surface' (S1), 'Going up or down stairs' (S2), 'at night while in bed' (S3), 'Sitting or lying' (S4), 'Standing upright' (S5)\]. The timepoints considered for the primary outcomes include baseline and week 4.

Outcome measures

Outcome measures
Measure	Diclofenac Sodium Gel n=318 Participants Diclofenac Sodium Gel, 1% Diclofenac sodium gel 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Voltaren® Gel n=330 Participants Voltaren® Gel (Diclofenac Sodium Topical Gel) 1% Voltaren® Gel (Diclofenac Sodium Topical Gel) 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Placebo Gel Placebo gel Placebo gel: Vehicle Gel 4 gm, 4 times a day for 4 weeks
Mean Change in the Total WOMAC Pain Subscale Score	-4.3 score on a scale Standard Deviation 2.64	-4.6 score on a scale Standard Deviation 2.64	—

PRIMARY outcome

Timeframe: 4 weeks

Population: The mITT Population was used for analysis of superiority of Mylan's Diclofenac gel and Voltaren gel over placebo. The primary outcome tested in this population was the superiority of Mylan's Diclofenac sodium gel (1%) and the Voltaren gel (1%) over placebo and thus all the three arms are presented here.

Mean change in the total WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain subscale score for the target knee was compared to determine the superiority of the Test Drug and Reference Listed Drug (RLD) over placebo. Measure Description: Western Ontario and McMaster Universities Osteoarthritis Index WOMAC pain subscale score (pain score = min 0 to max 20), was determined by the sum of subject's responses to five questions (S1-S5) using a 5-point Likert scale (i.e., 'none'=0; 'mild'=1, 'moderate'=2; 'severe'=3; 'extreme'=4). Higher values represent worse outcome. 'How much pain do you have' when 'Walking on a flat surface' (S1), 'Going up or down stairs' (S2), 'at night while in bed' (S3), 'Sitting or lying' (S4), 'Standing upright' (S5)\]. The timepoints considered for the primary outcomes include baseline and week 4.

Outcome measures

Outcome measures
Measure	Diclofenac Sodium Gel n=386 Participants Diclofenac Sodium Gel, 1% Diclofenac sodium gel 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Voltaren® Gel n=402 Participants Voltaren® Gel (Diclofenac Sodium Topical Gel) 1% Voltaren® Gel (Diclofenac Sodium Topical Gel) 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Placebo Gel n=396 Participants Placebo gel Placebo gel: Vehicle Gel 4 gm, 4 times a day for 4 weeks
Change From Baseline in WOMAC Pain Subscale Score	-4.2 score on a scale Standard Deviation 2.84	-4.4 score on a scale Standard Deviation 2.74	-3.2 score on a scale Standard Deviation 3.46

Adverse Events

Diclofenac Sodium Gel

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Voltaren® Gel

Serious events: 1 serious events

Other events: 19 other events

Deaths: 1 deaths

Placebo Gel

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Diclofenac Sodium Gel n=398 participants at risk Diclofenac Sodium Gel, 1% Diclofenac sodium gel 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Voltaren® Gel n=405 participants at risk Voltaren® Gel (Diclofenac Sodium Topical Gel) 1% Voltaren® Gel (Diclofenac Sodium Topical Gel) 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Placebo Gel n=400 participants at risk Placebo gel Placebo gel: Vehicle Gel 4 gm, 4 times a day for 4 weeks
Psychiatric disorders Completed Suicide	0.00% 0/398 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).	0.25% 1/405 • Number of events 1 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).	0.00% 0/400 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).

Other adverse events

Other adverse events
Measure	Diclofenac Sodium Gel n=398 participants at risk Diclofenac Sodium Gel, 1% Diclofenac sodium gel 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Voltaren® Gel n=405 participants at risk Voltaren® Gel (Diclofenac Sodium Topical Gel) 1% Voltaren® Gel (Diclofenac Sodium Topical Gel) 1%: Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks	Placebo Gel n=400 participants at risk Placebo gel Placebo gel: Vehicle Gel 4 gm, 4 times a day for 4 weeks
Nervous system disorders Headache	1.0% 4/398 • Number of events 5 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).	2.2% 9/405 • Number of events 12 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).	2.8% 11/400 • Number of events 14 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).
General disorders Pyrexia	1.5% 6/398 • Number of events 6 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).	1.5% 6/405 • Number of events 9 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).	2.2% 9/400 • Number of events 11 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).
Blood and lymphatic system disorders Eosinophilia	0.25% 1/398 • Number of events 1 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).	0.99% 4/405 • Number of events 4 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).	0.00% 0/400 • The reporting period for TEAEs started after the informed consent through day 28 after the last application of investigational product, a total of approximately 12 weeks. The safety analysis was performed based on safety population that includes all patients who were treated with at least one application of the investigational product. The total number of patients included in this population were 1203 (398 for Mylan's Diclofenac gel, 405 for Voltaren gel and 400 for placebo).

Additional Information

Dr. Prasanna C Ganapathi, Associate Vice President, Global Clinical Sciences

Mylan Pharmaceuticals Pvt Ltd.

Phone: 08066728952

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place