Trial Outcomes & Findings for Voltaren Emulgel 2% Acute Ankle Sprain Non Inferiority Study (NCT NCT04052620)

NCT ID: NCT04052620

Last Updated: 2022-04-12

Results Overview

The investigator performed a movement of the ankle and the pain assessment was done by the participant using a 100 mm VAS by describing ankle pain on movement. The POM was registered by the participant by drawing a perpendicular line on the 100 mm VAS with anchors at 0 = no pain and 100 = extreme pain. Higher scores indicate a worse outcome. Change from Baseline in POM was calculated by subtracting the Baseline value from the Day 5 value.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 313 participants
• Primary outcome timeframe: Baseline and Day 5
• Results posted on: 2022-04-12

Participant Flow

The study was conducted at 15 centers in China.

A total of 313 participants were enrolled into the study and 302 participants were randomized. Of these 150 participants were randomized to Diclofenac diethylamine (DDEA) 2.32 percent (%) gel twice daily (BID) and 152 were randomized to DDEA 1.16% gel four times daily (QID). A total of 288 participants completed the study.

Participant milestones

Measure	DDEA 2.32% Gel/Placebo The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Overall Study STARTED	150	152
Overall Study COMPLETED	143	145
Overall Study NOT COMPLETED	7	7

Reasons for withdrawal

Measure	DDEA 2.32% Gel/Placebo The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Overall Study aspartate aminotransferase (AST) >= 2 times upper limit of normal (ULN)	1	0
Overall Study Withdrawal by Subject	1	0
Overall Study Lost to Follow-up	1	1
Overall Study Adverse Event	1	0
Overall Study Subject did not meet study Criteria	0	1
Overall Study Screened failure, randomized by mistake	0	1
Overall Study Personal reasons	2	4
Overall Study alanine aminotransferase (ALT) >= 2 times ULN	1	0

Baseline Characteristics

Voltaren Emulgel 2% Acute Ankle Sprain Non Inferiority Study

Baseline characteristics by cohort

Measure	DDEA 2.32% Gel/Placebo n=150 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=152 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.	Total n=302 Participants Total of all reporting groups
Age, Continuous	34 Years STANDARD_DEVIATION 11.11 • n=5 Participants	34.1 Years STANDARD_DEVIATION 12.41 • n=7 Participants	34 Years STANDARD_DEVIATION 11.76 • n=5 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	69 Participants n=7 Participants	133 Participants n=5 Participants
Sex: Female, Male Male	86 Participants n=5 Participants	83 Participants n=7 Participants	169 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	150 Participants n=5 Participants	152 Participants n=7 Participants	302 Participants n=5 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 5

Population: Per Protocol (PP) Population: All participants from the Intent-to-Treat (modified) (mITT) population who did not have any major protocol deviations. mITT population comprise all randomized participants who had at least 1 post-Baseline POM VAS assessment.

The investigator performed a movement of the ankle and the pain assessment was done by the participant using a 100 mm VAS by describing ankle pain on movement. The POM was registered by the participant by drawing a perpendicular line on the 100 mm VAS with anchors at 0 = no pain and 100 = extreme pain. Higher scores indicate a worse outcome. Change from Baseline in POM was calculated by subtracting the Baseline value from the Day 5 value.

Outcome measures

Measure	DDEA 2.32% Gel/Placebo n=122 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=128 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Change From Baseline in Pain on Movement (POM) on Day 5 of Treatment as Assessed by a 100 Millimeter (mm) Visual Analogue Scale (VAS)	-42.36 mm Standard Error 1.49	-43.47 mm Standard Error 1.45

SECONDARY outcome

Timeframe: up to 28 days following last administration of the study product (or last procedure)

Population: Safety Population. It included all participants who were randomized and have received at least one dose of investigational product

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study product including any washout or lead-in product or investigational assessment, whether or not considered related to the study product. The investigator or medically qualified designee assessed the intensity for each AE reported during the study and categorized it on the basis of severity as Mild (an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities), Moderate (an event that is sufficiently discomforting to interfere with normal everyday activities or Severe (an event that prevents normal everyday activities).

Outcome measures

Measure	DDEA 2.32% Gel/Placebo n=150 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=151 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Number of Participants With Severity of Adverse Events (AEs) Following Dosing With Study Medication Mild	9 Participants	8 Participants
Number of Participants With Severity of Adverse Events (AEs) Following Dosing With Study Medication Moderate	2 Participants	4 Participants
Number of Participants With Severity of Adverse Events (AEs) Following Dosing With Study Medication Severe	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Days 3 and 8

Population: PP Population. Only those participants with available on-treatment data at the specified time points were analyzed.

The investigator performed a movement of the ankle and the pain assessment was done by the participant using a 100 mm VAS by describing ankle pain on movement. The POM was registered by the participant by drawing a perpendicular line on the 100 mm VAS with anchors at 0 = no pain and 100 = extreme pain. Higher scores indicate a worse outcome. Change from Baseline in POM on Day 3 and Day 8 was calculated by subtracting the Baseline value from the Day 3 and Day 8 values respectively.

Outcome measures

Measure	DDEA 2.32% Gel/Placebo n=122 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=128 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Change From Baseline of POM on VAS on Day 3 and Day 8 of Treatment Assessed by 100 mm VAS Day 3	-28.29 mm Standard Error 1.51	-25.86 mm Standard Error 1.48
Change From Baseline of POM on VAS on Day 3 and Day 8 of Treatment Assessed by 100 mm VAS Day 8	-55.38 mm Standard Error 1.25	-54.62 mm Standard Error 1.23

SECONDARY outcome

Timeframe: Baseline and Days 3, 5 and 8

Population: PP Population. Only those participants with available on-treatment data at the specified time points were analyzed.

'Tenderness' was the sensation of pain expressed by a participant when pressure was applied to the body. Tenderness was measured by calibrated algometers in an area of 1 cm^2 at the center of the injured area. The investigator applied the pressure gauge to the marked tender point of maximum sensitivity by placing the gauge at a 90 degree angle vertical to the skin. The participant was instructed to indicate the onset of pain with a verbal cue such as "Yes" or "Stop". Change from Baseline in tenderness on Day 3, 5 and 8 was calculated by subtracting the Baseline value from the Day 3, Day 5 and Day 8 values respectively

Outcome measures

Measure	DDEA 2.32% Gel/Placebo n=122 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=128 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Change From Baseline in Tenderness as Measured by Pressure Algometry on Days 3, 5 and 8 Day 3	6.92 Newton per square centimeter (N/cm^2) Standard Error 0.85	5.72 Newton per square centimeter (N/cm^2) Standard Error 0.83
Change From Baseline in Tenderness as Measured by Pressure Algometry on Days 3, 5 and 8 Day 5	9.84 Newton per square centimeter (N/cm^2) Standard Error 0.97	10.76 Newton per square centimeter (N/cm^2) Standard Error 0.94
Change From Baseline in Tenderness as Measured by Pressure Algometry on Days 3, 5 and 8 Day 8	17.06 Newton per square centimeter (N/cm^2) Standard Error 1.19	15.60 Newton per square centimeter (N/cm^2) Standard Error 1.16

SECONDARY outcome

Timeframe: Baseline and Days 3, 5 and 8

Population: PP Population. Only those participants with available on-treatment data at the specified time points were analyzed.

'Tenderness' was the sensation of pain expressed by a participant when pressure was applied to the body. Tenderness was measured by calibrated algometers in an area of 1 cm^2 at the center of the injured area. The investigator applied the pressure gauge to the marked tender point of maximum sensitivity by placing the gauge at a 90 degree angle vertical to the skin. The participant was instructed to indicate the onset of pain with a verbal cue such as "Yes" or "Stop". Difference in tenderness between affected ankle and contralateral ankle is presented. Change from Baseline in tenderness on Day 3, 5 and 8 was calculated by subtracting the Baseline value from the Day 3, Day 5 and Day 8 values respectively.

Outcome measures

Measure	DDEA 2.32% Gel/Placebo n=122 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=128 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Changes From Baseline in Difference of Tenderness Between Affected Ankle and Contralateral Ankle Measured by Algometry on Days 3, 5 and 8 Day 3	7.85 N/cm^2 Standard Error 0.90	7.59 N/cm^2 Standard Error 0.88
Changes From Baseline in Difference of Tenderness Between Affected Ankle and Contralateral Ankle Measured by Algometry on Days 3, 5 and 8 Day 5	11.34 N/cm^2 Standard Error 0.88	12.59 N/cm^2 Standard Error 0.86
Changes From Baseline in Difference of Tenderness Between Affected Ankle and Contralateral Ankle Measured by Algometry on Days 3, 5 and 8 Day 8	16.64 N/cm^2 Standard Error 1.03	14.98 N/cm^2 Standard Error 1.01

SECONDARY outcome

Timeframe: Baseline and Days 3, 5 and 8

Population: PP Population. Only those participants with available on-treatment data at the specified time points were analyzed.

Ankle Joint Function was assessed by the participants using Karlsson Scoring Scale. The scoring scale measured recovery of ankle joint function after an acute ligament injury. Assessments were made in the following eight categories (score): pain (20), swelling (10), instability (subjective) (15), stiffness (5), stair climbing (10), running (10), work activities (15), and the use of a support device (5). The total score ranges in value from 0 (worst possible score) to 90 (best possible score). Change from Baseline in the ankle joint function on Days 3, 5 and 8 was calculated by subtracting the Baseline value from the Day 3, Day 5 and Day 8 values respectively.

Outcome measures

Measure	DDEA 2.32% Gel/Placebo n=122 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=128 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Change From Baseline in Ankle Joint Function (Karlsson Scoring Scale) on Days 3, 5 and 8 Day 3	16.26 Scores on a scale Standard Error 1.07	15.52 Scores on a scale Standard Error 1.05
Change From Baseline in Ankle Joint Function (Karlsson Scoring Scale) on Days 3, 5 and 8 Day 5	27.94 Scores on a scale Standard Error 1.46	28.22 Scores on a scale Standard Error 1.43
Change From Baseline in Ankle Joint Function (Karlsson Scoring Scale) on Days 3, 5 and 8 Day 8	41.87 Scores on a scale Standard Error 1.59	39.75 Scores on a scale Standard Error 1.56

SECONDARY outcome

Timeframe: Baseline and Days 3, 5 and 8

Population: PP Population. Only those participants with available on-treatment data at the specified time points were analyzed.

Each participant was seated comfortably in a long sitting position with both feet extended beyond the end of the plinth in a slight dorsiflexion position. The Figure of Eight Method was applied to both feet and the tape measure was wrapped around the ankle along the following course: the beginning of the tape was placed midway between the tibialis anterior tendon and lateral malleolus and was then continued across anatomically defined points in the form of a figure of eight around the ankle joint. The tape localization of the first measurement was marked with an appropriate marker. Each ankle was measured three times and the average was calculated. Change from Baseline in circumference on Days 3, 5 and 8 was calculated by subtracting the Baseline value from the Day 3, Day 5 and Day 8 values respectively.

Outcome measures

Measure	DDEA 2.32% Gel/Placebo n=122 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=128 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Change From Baseline in Circumference of Affected Ankle (Swelling) as Measured by Figure of Eight Method on Days 3, 5 and 8 Day 3	-0.42 Centimeter (cm) Standard Error 0.09	-0.24 Centimeter (cm) Standard Error 0.09
Change From Baseline in Circumference of Affected Ankle (Swelling) as Measured by Figure of Eight Method on Days 3, 5 and 8 Day 5	-0.97 Centimeter (cm) Standard Error 0.10	-0.57 Centimeter (cm) Standard Error 0.10
Change From Baseline in Circumference of Affected Ankle (Swelling) as Measured by Figure of Eight Method on Days 3, 5 and 8 Day 8	-1.25 Centimeter (cm) Standard Error 0.10	-0.87 Centimeter (cm) Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline and Days 3, 5 and 8

Population: PP Population. Only those participants with available on-treatment data at the specified time points were analyzed.

Each participant was seated comfortably in a long sitting position with both feet extended beyond the end of the plinth in a slight dorsiflexion position. The Figure of Eight Method was applied to both feet and the tape measure was wrapped around the ankle along the following course: the beginning of the tape was placed midway between the tibialis anterior tendon and lateral malleolus and was then continued across anatomically defined points in the form of a figure of eight around the ankle joint. The tape localization of the first measurement was marked with an appropriate marker. Each ankle was measured three times and the average was calculated. Difference of circumference (swelling) between affected ankle and contralateral ankle is presented. Change from Baseline in circumference on Days 3, 5 and 8 was calculated by subtracting the Baseline value from the Day 3, Day 5 and Day 8 values respectively.

Outcome measures

Measure	DDEA 2.32% Gel/Placebo n=122 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=128 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Change From Baseline in Difference of Circumference (Swelling) Between Affected Ankle and Contralateral Ankle by Figure of Eight Method on Days 3, 5 and 8 Day 3	-0.41 cm Standard Error 0.07	-0.29 cm Standard Error 0.06
Change From Baseline in Difference of Circumference (Swelling) Between Affected Ankle and Contralateral Ankle by Figure of Eight Method on Days 3, 5 and 8 Day 5	-0.83 cm Standard Error 0.07	-0.66 cm Standard Error 0.06
Change From Baseline in Difference of Circumference (Swelling) Between Affected Ankle and Contralateral Ankle by Figure of Eight Method on Days 3, 5 and 8 Day 8	-1.12 cm Standard Error 0.06	-0.92 cm Standard Error 0.06

SECONDARY outcome

Timeframe: 0 to 24 hours (Day 1) and 96 to 120 hours (Day 5) post first dose

Population: PP Population. Only those participants with available on-treatment data at the specified time points were analyzed.

Pain intensity was assessed in the diary on a categorical scale ranging from 0 to 3, where 0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = severe pain. A higher value indicates more severe pain. Pain intensity was assessed at Baseline (immediately prior to first dose) and every 2 hours (after starting study product) until the participant went to bed on the evening of Day 1. The same assessment and recording frequency were also followed starting with the first dose on Day 5.

Outcome measures

Measure	DDEA 2.32% Gel/Placebo n=122 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=126 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Sum of Pain Intensity Difference (SPID) From 0 to 24 Hours Post First Dose (Day 1) and From 96 to 120 Hours Post First Dose (Day 5) Sum of 0 - 12 hours post first dose (Day 1)	15.80 Scores on a scale Standard Error 0.583	15.43 Scores on a scale Standard Error 0.574
Sum of Pain Intensity Difference (SPID) From 0 to 24 Hours Post First Dose (Day 1) and From 96 to 120 Hours Post First Dose (Day 5) Sum of 96 - 120 hours post first dose (Day 5)	9.80 Scores on a scale Standard Error 0.512	10.29 Scores on a scale Standard Error 0.503

SECONDARY outcome

Timeframe: 0 to 24 hours (Day 1) and 96 to 120 hours (Day 5) post first dose

Population: PP Population. Only those participants with available on-treatment data at the specified time points were analyzed.

Pain relief was assessed in the diary on a categorical scale ranging from 0 to 4, where 0 = no relief, 1 = a little relief, 2 = some relief, 3 = a lot of relief, 4 = complete relief. A higher value indicates greater pain relief. Pain relief was assessed at Baseline (immediately prior to first dose) and every 2 hours (after starting study product) until the participant went to bed on the evening of Day 1. The same assessment and recording frequency were also followed starting with the first dose on Day 5.

Outcome measures

Measure	DDEA 2.32% Gel/Placebo n=122 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=126 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Total Pain Relief (TOTPAR) From 0 to 24 Hours Post First Dose (Day 1) and From 96 to 120 Hours Post First Dose (Day 5) Sum of 0-12 hours post first dose (Day 1)	8.47 Scores on a scale Standard Error 0.585	8.53 Scores on a scale Standard Error 0.575
Total Pain Relief (TOTPAR) From 0 to 24 Hours Post First Dose (Day 1) and From 96 to 120 Hours Post First Dose (Day 5) Sum of 96-120 hours post first dose (Day 5)	28.48 Scores on a scale Standard Error 1.030	27.68 Scores on a scale Standard Error 1.014

SECONDARY outcome

Timeframe: Up to Day 8

Population: ITT Population. Only those participants who used rescue medication were analyzed.

Participants were instructed to take only the rescue medication provided for pain in the ankle or any other pain (for example, headache) or fever (for example, due to common cold) they experienced during the trial. One tablet was taken, repeated after at least 4 hours, if needed, up to a maximum of 2000 milligram (mg) (4 tablets) per day. No rescue medication was allowed within 6 hours prior to the study visits or within 12 hours of study Visit 3.

Outcome measures

Measure	DDEA 2.32% Gel/Placebo n=8 Participants The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=12 Participants The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Mean Number of Rescue Medication Tablets Used to Treat Ankle Pain	2.4 Number of Tablets Standard Deviation 2.39	2.6 Number of Tablets Standard Deviation 2.19

SECONDARY outcome

Timeframe: Up to Day 8

Population: ITT Population. Data was not collected for this outcome measure.

Data was not estimable as end date data for rescue medication use was not collected.

Outcome measures

Outcome data not reported

Adverse Events

DDEA 2.32% Gel/Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

DDEA 1.16% Gel

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	DDEA 2.32% Gel/Placebo n=150 participants at risk The participants were instructed to apply approximately 2 g DDEA 2.32% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning and in the late afternoon for 7 days. Similarly, participants were instructed to apply placebo gel at noon and in the late evening for 7 days. The very first dose was applied at the study center.	DDEA 1.16% Gel n=151 participants at risk The participants were instructed to apply approximately 2 g DDEA 1.16% gel topically with the fingertips to both sides of affected ankle which corresponds to a region of approximately 200 cm\^2 for approximately 1 minute in the morning, at noon, in the late afternoon, and in the late evening for 7 days. The very first dose was applied at the study center.
Blood and lymphatic system disorders Anaemia	0.67% 1/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.00% 0/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Gastrointestinal disorders Diarrhoea	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Gastrointestinal disorders Toothache	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
General disorders Application site inflammation	0.67% 1/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.00% 0/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Infections and infestations Gastroenteritis	1.3% 2/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.00% 0/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Infections and infestations Conjunctivitis	0.67% 1/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.00% 0/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Injury, poisoning and procedural complications Soft tissue injury	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Investigations Aspartate aminotransferase increased	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Investigations Blood glucose increased	0.67% 1/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.00% 0/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Metabolism and nutrition disorders Hyperglycaemia	0.67% 1/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.00% 0/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Musculoskeletal and connective tissue disorders Tenosynovitis	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Nervous system disorders Dizziness	0.67% 1/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.00% 0/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Nervous system disorders Headache	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Psychiatric disorders Insomnia	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Reproductive system and breast disorders Endometrial thickening	0.67% 1/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.00% 0/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.67% 1/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Skin and subcutaneous tissue disorders Eczema	0.67% 1/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.00% 0/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Skin and subcutaneous tissue disorders Rash	0.00% 0/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.66% 1/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.
Skin and subcutaneous tissue disorders Skin exfoliation	0.67% 1/150 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.	0.00% 0/151 • From screening up to 28 days following last administration of the study product (or last procedure). Treatment emergent AEs were defined as any new AE that occurred on or after the date/time of the first administration of study product, or any pre-existing AE that was considered to have worsened on or after the date/time of the first administration of study product.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 8664357343

Email: GSKClinicalSupportHD@gsk.com

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER