Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2016L09875 | Registry Identifier | NMPA |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to evaluate the efficacy and safety of diclofenac diethylamine 2.32 percent (%) gel applied twice daily versus diclofenac diethylamine 1.16% gel applied four times daily for 7 days in participants with acute ankle sprain.
This study is a Phase III, randomized, double blind, multi-center, active controlled, 2-treatment arm, parallel group, non-inferiority study to evaluate the efficacy and safety of diclofenac diethylamine 2.32% gel applied twice daily versus diclofenac diethylamine 1.16% gel applied four times daily for 7 days in participants with acute ankle sprain. The participants who experience an acute Grade I -II ankle sprain within the past 24 hours, and pain on movement of at least 50 millimeter (mm) on a 100 mm visual analogue scale (VAS) and who will meet all inclusion and exclusion criteria will be randomized in a 1:1 ratio, immediately post injury. All participants will receive 4 tubes of study drug, for treatment in morning, noon, late afternoon, and late evening, respectively. The very first dose of study drug will be applied at the study center. The participants will be instructed to apply the gel topically with the finger tips for approximately 1 minute in the morning, at noon, late afternoon, and late evening for 7 days. Each tube will be labeled for use at one of these 4 times. After the randomization visit (Visit 1/baseline visit- Day 1), participants will return to the study site for post baseline visits- Visit 2 (Day 3), Visit 3 (Day 5), and Visit 4 (Day 8 +/- 1 d) to complete efficacy and safety assessments. Baseline safety laboratory test blood samples will be taken at Visit 1. End of study safety laboratory tests will be performed at Visit 4, or in case of early termination on the day of termination. In addition, the participants (ex-clinic) will assess pain intensity and pain relief at frequent intervals on Day 1 and then at each study drug application throughout the rest of the study.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diclofenac diethylamine (DDEA) 2.32%/ Placebo gel | Experimental | Participants will receive 4 tubes, DDEA 2.32% gel and Placebo gel (2 each) and instructed to apply the gel 5 centimeter (cm) topically with the finger tips (for approximately 1 minute) on both sides of affected ankle on area of approximately 200 square centimeters (cm^2). DDEA 2.32% gel will be applied in morning and late afternoon and Placebo gel will be applied in noon and late evening for 7 days. |
|
| DDEA 1.16% gel | Active Comparator | Participants will receive 4 tubes of DDEA 1.16% gel and instructed to apply the gel 5 centimeter (cm) topically with the finger tips (for approximately 1 minute) on both sides of affected ankle on area of approximately 200 square centimeters (cm^2) in morning, noon, late afternoon, and late evening for 7 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Diclofenac diethylamine 2.32% gel | Drug | Participants will apply DDEA 2.32% gel topically with the finger tips (for approximately 1 minute) on both sides of affected ankle 5 cm on 200 cm^2 two times daily for 7 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Pain on Movement (POM) on Day 5 of Treatment as Assessed by a 100 Millimeter (mm) Visual Analogue Scale (VAS) | 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. | Baseline and Day 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Severity of Adverse Events (AEs) Following Dosing With Study Medication | 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). |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Guangzhou | Guangdong | 510630 | China | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36566202 | Derived | Yin F, Ma J, Xiao H, Ao R, Zhang F, Li W, Wang W, Zeng P, Lu T, Revel FB, Araga M, Patel S, Moreira S, Zhang J, Zhang W. Randomized, double-blind, noninferiority study of diclofenac diethylamine 2.32% gel applied twice daily versus diclofenac diethylamine 1.16% gel applied four times daily in patients with acute ankle sprain. BMC Musculoskelet Disord. 2022 Dec 24;23(1):1125. doi: 10.1186/s12891-022-06077-z. |
Not provided
Not provided
IPD for this study will be made available via the Clinical Study Data Request site.
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension can be grated, when justified, for up to another 12 months.
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.
The study was conducted at 15 centers in China.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-treat (ITT) population: Comprise all randomized participants. This population was based on the treatment to which the participant was randomized. Any participant who received a treatment randomization number was considered to have been randomized.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Pain on Movement (POM) on Day 5 of Treatment as Assessed by a 100 Millimeter (mm) Visual Analogue Scale (VAS) | 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. | 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. | Posted | Least Squares Mean | Standard Error | mm | Baseline and Day 5 |
|
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 23.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 8664357343 | GSKClinicalSupportHD@gsk.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 10, 2019 | Feb 14, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 20, 2021 | Nov 11, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D010146 | Pain |
| D016512 | Ankle Injuries |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007869 | Leg Injuries |
Not provided
Not provided
| ID | Term |
|---|---|
| C000614065 | diclofenac diethylamine |
| D005782 | Gels |
| ID | Term |
|---|---|
| D003102 | Colloids |
| D045424 | Complex Mixtures |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Diclofenac diethylamine 1.16% gel | Drug | Participants will apply DDEA 1.16 % gel topically with the finger tips (for approximately 1 minute) on both sides of affected ankle 5 cm on 200 cm^2 four times daily for 7 days. |
|
| Placebo | Other | Participants will apply Placebo gel topically with the finger tips (for approximately 1 minute) on both sides of affected ankle 5 cm on 200 cm^2 two times daily for 7 days. |
|
| up to 28 days following last administration of the study product (or last procedure) |
| Change From Baseline of POM on VAS on Day 3 and Day 8 of Treatment Assessed by 100 mm VAS | 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. | Baseline and Days 3 and 8 |
| Change From Baseline in Tenderness as Measured by Pressure Algometry on Days 3, 5 and 8 | '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 | Baseline and Days 3, 5 and 8 |
| Changes From Baseline in Difference of Tenderness Between Affected Ankle and Contralateral Ankle Measured by Algometry on Days 3, 5 and 8 | '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. | Baseline and Days 3, 5 and 8 |
| Change From Baseline in Ankle Joint Function (Karlsson Scoring Scale) on Days 3, 5 and 8 | 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. | Baseline and Days 3, 5 and 8 |
| Change From Baseline in Circumference of Affected Ankle (Swelling) as Measured by Figure of Eight Method on Days 3, 5 and 8 | 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. | Baseline and Days 3, 5 and 8 |
| 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 | 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. | Baseline and Days 3, 5 and 8 |
| 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) | 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. | 0 to 24 hours (Day 1) and 96 to 120 hours (Day 5) post first dose |
| 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) | 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. | 0 to 24 hours (Day 1) and 96 to 120 hours (Day 5) post first dose |
| Mean Number of Rescue Medication Tablets Used to Treat Ankle Pain | 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. | Up to Day 8 |
| Number of Days on Which Rescue Medication Was Used to Treat Ankle Pain | Data was not estimable as end date data for rescue medication use was not collected. | Up to Day 8 |
| Shenzhen |
| Guangdong |
| 100730 |
| China |
| GSK Investigational Site | Shenzhen | Guangdong | 518053 | China |
| GSK Investigational Site | Shijiazhuang | Hebei | 050051 | China |
| GSK Investigational Site | Chenzhou | Hunan | 423000 | China |
| GSK Investigational Site | Dalian | Liaoning | 116001 | China |
| GSK Investigational Site | Shenyang | Liaoning | 110044 | China |
| GSK Investigational Site | Xi'an | Shaanxi | 710061 | China |
| GSK Investigational Site | Kunming | Yunnan | 650032 | China |
| GSK Investigational Site | Beijing | 101200 | China |
| GSK Investigational Site | Shanghai | 200025 | China |
| GSK Investigational Site | Shanghai | 200080 | China |
| GSK Investigational Site | Shanghai | 200120 | China |
| GSK Investigational Site | Shanghai | 201449 | China |
| Lost to Follow-up |
|
| Adverse Event |
|
| Subject did not meet study Criteria |
|
| Screened failure, randomized by mistake |
|
| Personal reasons |
|
| alanine aminotransferase (ALT) >= 2 times ULN |
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | 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.
| OG001 | 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. |
|
|
|
| Secondary | Number of Participants With Severity of Adverse Events (AEs) Following Dosing With Study Medication | 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). | Safety Population. It included all participants who were randomized and have received at least one dose of investigational product | Posted | Count of Participants | Participants | up to 28 days following last administration of the study product (or last procedure) |
|
|
|
| Secondary | Change From Baseline of POM on VAS on Day 3 and Day 8 of Treatment Assessed by 100 mm VAS | 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. | PP Population. Only those participants with available on-treatment data at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | mm | Baseline and Days 3 and 8 |
|
|
|
|
| Secondary | Change From Baseline in Tenderness as Measured by Pressure Algometry on Days 3, 5 and 8 | '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 | PP Population. Only those participants with available on-treatment data at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Newton per square centimeter (N/cm^2) | Baseline and Days 3, 5 and 8 |
|
|
|
|
| Secondary | Changes From Baseline in Difference of Tenderness Between Affected Ankle and Contralateral Ankle Measured by Algometry on Days 3, 5 and 8 | '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. | PP Population. Only those participants with available on-treatment data at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | N/cm^2 | Baseline and Days 3, 5 and 8 |
|
|
|
|
| Secondary | Change From Baseline in Ankle Joint Function (Karlsson Scoring Scale) on Days 3, 5 and 8 | 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. | PP Population. Only those participants with available on-treatment data at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Scores on a scale | Baseline and Days 3, 5 and 8 |
|
|
|
|
| Secondary | Change From Baseline in Circumference of Affected Ankle (Swelling) as Measured by Figure of Eight Method on Days 3, 5 and 8 | 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. | PP Population. Only those participants with available on-treatment data at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Centimeter (cm) | Baseline and Days 3, 5 and 8 |
|
|
|
|
| Secondary | 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 | 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. | PP Population. Only those participants with available on-treatment data at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | cm | Baseline and Days 3, 5 and 8 |
|
|
|
|
| Secondary | 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) | 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. | PP Population. Only those participants with available on-treatment data at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Scores on a scale | 0 to 24 hours (Day 1) and 96 to 120 hours (Day 5) post first dose |
|
|
|
|
| Secondary | 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) | 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. | PP Population. Only those participants with available on-treatment data at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Scores on a scale | 0 to 24 hours (Day 1) and 96 to 120 hours (Day 5) post first dose |
|
|
|
|
| Secondary | Mean Number of Rescue Medication Tablets Used to Treat Ankle Pain | 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. | ITT Population. Only those participants who used rescue medication were analyzed. | Posted | Mean | Standard Deviation | Number of Tablets | Up to Day 8 |
|
|
|
| Secondary | Number of Days on Which Rescue Medication Was Used to Treat Ankle Pain | Data was not estimable as end date data for rescue medication use was not collected. | ITT Population. Data was not collected for this outcome measure. | Posted | Up to Day 8 |
|
|
| 0 |
| 150 |
| 0 |
| 150 |
| 11 |
| 150 |
| EG001 | 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. | 0 | 151 | 0 | 151 | 12 | 151 |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Application site inflammation | General disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA Version 23.0 | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA Version 23.0 | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Systematic Assessment |
|
| Soft tissue injury | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Tenosynovitis | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Endometrial thickening | Reproductive system and breast disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
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.
| D014947 | Wounds and Injuries |
| Severe |
|
| Day 8 |
|
|
| 0.6643 |
| Mean Difference (Final Values) |
| -0.76 |
| Standard Error of the Mean |
| 1.76 |
| 2-Sided |
| 95 |
| -4.23 |
| 2.70 |
DDEA 2.32% gel vs DDEA 1.16% gel, Day 8 |
| Other |
| Day 5 |
|
|
| Day 8 |
|
|
| 0.4937 |
| Mean Difference (Final Values) |
| -0.93 |
| Standard Error of the Mean |
| 1.35 |
| 2-Sided |
| 95 |
| -3.60 |
| 1.74 |
DDEA 2.32% gel vs DDEA 1.16% gel, Day 5 |
| Other |
| ANCOVA | 0.3825 | Mean Difference (Final Values) | 1.46 | Standard Error of the Mean | 1.67 | 2-Sided | 95 | -1.83 | 4.74 | DDEA 2.32% gel vs DDEA 1.16% gel, Day 8 | Other |
| Day 5 |
|
|
| Day 8 |
|
|
| 0.3119 |
| Mean Difference (Final Values) |
| -1.25 |
| Standard Error of the Mean |
| 1.24 |
| 2-Sided |
| 95 |
| -3.69 |
| 1.18 |
DDEA 2.32% gel vs DDEA 1.16% gel, Day 5 |
| Other |
| ANCOVA | 0.2535 | Mean Difference (Final Values) | 1.66 | Standard Error of the Mean | 1.45 | 2-Sided | 95 | -1.20 | 4.52 | DDEA 2.32% gel vs DDEA 1.16% gel, Day 8 | Other |
| Day 5 |
|
|
| Day 8 |
|
|
| 0.8905 |
| Mean Difference (Final Values) |
| -0.28 |
| Standard Error of the Mean |
| 2.06 |
| 2-Sided |
| 95 |
| -4.33 |
| 3.77 |
DDEA 2.32% gel vs DDEA 1.16% gel, Day 5 |
| Other |
| ANCOVA | 0.3439 | Mean Difference (Final Values) | 2.12 | Standard Error of the Mean | 2.24 | 2-Sided | 95 | -2.29 | 6.54 | DDEA 2.32% gel vs DDEA 1.16% gel, Day 8 | Other |
| Day 5 |
|
|
| Day 8 |
|
|
| 0.0047 |
| Mean Difference (Final Values) |
| -0.39 |
| Standard Error of the Mean |
| 0.14 |
| 2-Sided |
| 95 |
| -0.66 |
| -0.12 |
DDEA 2.32% gel vs DDEA 1.16% gel, Day 5 |
| Other |
| ANCOVA | 0.0082 | Mean Difference (Final Values) | -0.38 | Standard Error of the Mean | 0.14 | 2-Sided | 95 | -0.66 | -0.10 | DDEA 2.32% gel vs DDEA 1.16% gel, Day 8 | Other |
| Day 5 |
|
|
| Day 8 |
|
|
| 0.0574 |
| Mean Difference (Final Values) |
| -0.18 |
| Standard Error of the Mean |
| 0.09 |
| 2-Sided |
| 95 |
| -0.36 |
| 0.01 |
DDEA 2.32% gel vs DDEA 1.16% gel, Day 5 |
| Other |
| ANCOVA | 0.0194 | Mean Difference (Final Values) | -0.20 | Standard Error of the Mean | 0.08 | 2-Sided | 95 | -0.37 | -0.03 | DDEA 2.32% gel vs DDEA 1.16% gel, Day 8 | Other |
| 0.4924 |
| Mean Difference (Final Values) |
| -0.50 |
| Standard Error of the Mean |
| 0.721 |
| 2-Sided |
| 95 |
| -1.915 |
| 0.924 |
DDEA 2.32% gel vs DDEA 1.16% gel, Day 5 |
| Other |
| 0.5820 |
| Mean Difference (Final Values) |
| 0.80 |
| Standard Error of the Mean |
| 1.451 |
| 2-Sided |
| 95 |
| -2.059 |
| 3.659 |
DDEA 2.32% gel vs DDEA 1.16% gel, Day 5 |
| Other |