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Voltaren Emulgel 2% Acute Ankle Sprain Non Inferiority Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04052620
Recruitment Status : Not yet recruiting
First Posted : August 12, 2019
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pain Drug: Diclofenac diethylamine 2.32% gel Drug: Diclofenac diethylamine 1.16% gel Other: Placebo Phase 3

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 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 Versus 1.16% Gel in Subjects With Acute Ankle Sprain
Estimated Study Start Date : September 11, 2019
Estimated Primary Completion Date : September 18, 2020
Estimated Study Completion Date : September 18, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Diclofenac diethylamine (DDEA) 2.32%/ Placebo gel
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.
Drug: Diclofenac diethylamine 2.32% gel
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.

Other: Placebo
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.

Active Comparator: DDEA 1.16% gel
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.
Drug: Diclofenac diethylamine 1.16% gel
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.




Primary Outcome Measures :
  1. Change from Baseline in Pain on Movement (POM) on Day 5 of Treatment as Assessed by a 100 Millimeter (mm) Visual Analogue Scale (VAS) [ Time Frame: Baseline and Day 5 ]
    Participant will lie down on an even horizontal surface and investigator will gently lift the leg and hold it up in the air at an angle of approximately 45 degrees. While holding the leg with one hand, the investigator will perform a gentle inversion of the foot of the injured ankle to reach an angle of approx. 30 degrees. The extent of ankle pain will be evaluated by the participant in answer to the question: "How would you describe your ankle pain right now?" The pain-on-movement will be registered by the participant by drawing a perpendicular line on the 100 mm VAS scale with anchors at 0 = "no pain" and 100 = "extreme pain". Change from baseline in POM will be calculated by subtracting the baseline value from the Day 5 value.


Secondary Outcome Measures :
  1. Number, Incidence and Severity of Adverse Events Following Dosing With Study Medication [ Time Frame: Up to Day 8 ]

    Safety will be assessed by evaluating the number, incidence and severity of adverse events (AEs).

    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, including any washout or lead-in product or investigational assessment.


  2. Change From Baseline in Pain on Movement (POM) on Day 3 and Day 8 of Treatment as Assessed by 100 mm VAS scale [ Time Frame: Baseline, Day 3 and Day 8 ]
    Participant will lie down on an even horizontal surface and investigator will gently lift the leg and hold it up in the air at an angle of approximately 45 degrees. While holding the leg with one hand, the investigator will perform a gentle inversion of the foot of the injured ankle to reach an angle of approx. 30 degrees. The extent of ankle pain will be evaluated by the participant in answer to the question: "How would you describe your ankle pain right now?" The pain-on-movement will be registered by the participant by drawing a perpendicular line on the 100 mm VAS scale with anchors at 0 = "no pain" and 100 = "extreme pain". Change from baseline in POM will be calculated by subtracting the baseline value from the Day 3 and Day 8 values respectively.

  3. Change From Baseline in Tenderness as Measured by Pressure Algometry on Days 3, 5 and 8 [ Time Frame: Baseline, Day 3, Day 5 and Day 8 ]
    The tenderness will be measured by applying pressure in an area of 1 cm^2 at the center of the injured area, using a handheld pressure algometer. The investigator will apply the pressure gauge to the marked tender point of maximum sensitivity by placing the gauge at 90 degrees angle vertical to the skin. The pressure pain threshold will be estimated by instructing participants to say 'stop' when the sensation of pressure becomes the first sensation of pain. Change from baseline in tenderness will be calculated by subtracting the baseline value from the Day 3, Day 5 and Day 8 values respectively.

  4. Difference Between the Tenderness Measurement of Affected Ankle and Contralateral Ankle on Days 3, 5 and 8 [ Time Frame: Day 3, Day 5 and Day 8 ]
    The tenderness will be measured by applying pressure in an area of 1 cm^2 at the center of the injured area, using a handheld pressure algometer. The investigator will apply the pressure gauge to the marked tender point of maximum sensitivity by placing the gauge at 90 degrees angle vertical to the skin. The pressure pain threshold will be estimated by instructing participants to say 'stop' when the sensation of pressure becomes the first sensation of pain. Difference between tenderness of treated painful area and corresponding anatomical position of the healthy uninjured contralateral side will be measured at Days 3, 5 and 8 to assess the efficacy of treatment in inflammation.

  5. Change From Baseline in Ankle Joint Function on Days 3, 5 and 8 as Assessed by Karlsson Scoring Scale [ Time Frame: Baseline, Day 3, Day 5 and Day 8 ]
    Karlsson Scoring scale is a validated scoring scale which measures the recovery of ankle joint function after an acute ligament injury. Assessments will be made in the 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). Total score ranges from 0 "worst possible score" to 90 "best possible score". Change from baseline in the ankle joint function will be calculated by subtracting the baseline value from the Day 3, Day 5 and Day 8 values respectively.

  6. Change From Baseline in Circumference of Affected Ankle as Measured by Figure of Eight Method on Days 3, 5 and 8 [ Time Frame: Baseline, Day 3, Day 5 and Day 8 ]
    One-quarter-inch wide (about 63 mm), retractable, plastic tape measure will be utilized to the measurements of each participant's ankle in centimeters (cm). Each participant will be 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 will be applied to both feet and the tape measure will be wrapped around the ankle along the following course: the beginning of the tape placed midway between the tibialis anterior tendon and lateral malleolus and 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 would be marked with an appropriate marker. Each ankle will be measured three times and the average will be calculated. Change from baseline in circumference will be calculated by subtracting the baseline value from the Day 3, Day 5 and Day 8 values respectively.

  7. Difference Between Circumference of Affected Ankle to Unaffected Ankle by Figure of Eight Method on Days 3, 5, and 8 [ Time Frame: Day 3, Day 5 and Day 8 ]
    One-quarter-inch wide (about 63 mm), retractable, plastic tape measure will be utilized to the measurements of each participant's ankle in cm. Each participant will be 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 will be applied to both feet and the tape measure will be wrapped around the ankle along the following course: the beginning of the tape placed midway between the tibialis anterior tendon and lateral malleolus and 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 would be marked with an appropriate marker. Each ankle will be measured three times and the average will be calculated. The difference in this average between ankles tracks the natural course of disease on Day 3, Day 5 and Day 8.

  8. Sum of Pain Intensity Difference (SPID) From 0 - 24 Hours Post First Dose (Day 1) and From 96 - 120 Hours Post First Dose (Day 5) [ Time Frame: From 0 - 24 hours post first dose (Day 1) and from 96 - 120 hours post first dose (Day 5) ]
    SPID will be calculated from the equation: SPIDt = ΣPIDt (timet - timet-1)(h); where PI= pain intensity (measured on 100 mm VAS scale with anchors at 0 = "no pain" and 100 = "extreme pain"), t= time in hours post first dose (0-24 hours for Day 1 and 96-120 hours for Day 5 calculations). A higher value in SPID indicates greater pain relief.

  9. Total Pain Relief (TOTPAR) From 0 - 24 Hours Post First Dose (Day 1) and From 96 - 120 Hours Post First Dose (Day 5) [ Time Frame: From 0 - 24 hours post first dose (Day 1) and from 96 - 120 hours post first dose (Day 5) ]
    TOTPAR will be calculated from the equation: TOTPAR = ΣRt x (timet - timet-1); where Rt = the pain relief score at time t and time t = time in hours post first dose. Pain relief scores will be measured by using a 5 point categorical pain relief rating scale. (None = 0, A Little Relief = 1, Some = 2, A Lot = 3, Complete Relief = 4). The minimum possible TOTPAR 6 score = 0, maximum possible score = 24.

  10. Number of Tablets Used to Treat Ankle Pain and Overall [ Time Frame: Up to Day 8 ]
    Rescue medication (paracetamol, 500 milligrams [mg] tablets) will be provided to participants and instructed to take only for pain in the ankle or any other pain (e.g., headache) or fever (e.g., due to common cold) they might experience during the trial. One or two tablets may be taken, repeated after at least 4 hours, if needed, up to a maximum of 2000 mg (four tablets) per day. Number of tablets used to treat ankle pain and overall tablets used will be counted separately from the participant's diary. Average of all tablets used in all participants will be reported.

  11. Number of Days on Which Rescue Medication was Used to Treat Ankle Pain and Overall [ Time Frame: Up to Day 8 ]
    Rescue medication (paracetamol, 500 mg tablets) will be provided to participants and instructed to take only for pain in the ankle or any other pain (e.g., headache) or fever (e.g., due to common cold) they might experience during the trial. One or two tablets may be taken, repeated after at least 4 hours, if needed, up to a maximum of 2000 mg (four tablets) per day. Number of days on which the rescue medication used to treat ankle pain and overall will be counted from the participant's diary. Average of all days on which medication was used in all participants will be reported.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participant provision of a signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment will be performed.
  • A participant who is willing and able to comply with scheduled visits, treatment plan and other study procedures.
  • A participant with acute sprain of the lateral ankle on one side only, Grade I-II.
  • A participant who had pain-on-movement greater than or equal to (>=) 50 mm on a 100 mm VAS.
  • A participant with injury within the past 24 hours before randomization.
  • Participant had not taken pain medication within the 24 hours that precedes randomization.Treatment by rest, ice, compression, or elevation (RICE) is authorized prior to randomization. Stable daily doses of acetylsalicylic acid (less than or equal to [<=] 162 mg) taken for at least 30 days prior to the first dose of study medication for non-analgesic reasons may be continued for the duration of the study.
  • A participant in good general and mental health with, in the opinion of the investigator or medically qualified designee with no clinically significant/relevant abnormalities in medical history or upon physical examination, or condition, that would impact the participant's safety, wellbeing or the outcome of the study, if they were to participate in the study, or affect the individual's ability to understand and follow study procedures and requirements.
  • Female participant of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for 14 days after the last dose of assigned treatment.

Exclusion Criteria:

  • A participant with Grade I-III sprain of the affected ankle during the past 3 months.
  • A participant with Grade II-III sprain, any other significant injury (such as fracture or torn ligament), or surgery (except for skin or nails) of the affected ankle or foot during the past 6 months.
  • A participant with pain or instability in the affected ankle attributable to previous ankle sprain or any other trauma.
  • A participant with ankle sprain attributable to a known disease affecting the ligaments, such as ligament hyperlaxity due to connective tissue diseases (e.g. Marfan's syndrome, Down's syndrome, Ehlers-Danlos syndrome).
  • A participant who has any skin lesion or wound in the area to be treated.
  • A participant who intent to undergo surgery during time of participation.
  • A participant who is an employee of the investigational site, either directly involved in the conduct of the study or a member of their immediate family; or an employee of the investigational site otherwise supervised by the investigator; or, a GSK CH employee directly involved in the conduct of the study or a member of their immediate family.
  • A participant with,in the opinion of the investigator or medically qualified designee, an acute or chronic medical, including other current acute or chronic pain conditions, or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator or medically qualified designee, would make the participant inappropriate for entry into this study.
  • A participant who is a pregnant female.
  • A participant who is a breastfeeding female.
  • A participant with known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.
  • A participant who, in the opinion of the investigator or medically qualified designee, should not participate in the study.
  • A participant unwilling or unable to comply with the Lifestyle Considerations below: a) Participants must abstain from all food and drink (except water) at least 4 hours prior to any safety laboratory evaluations. b) Participants will abstain from caffeine-containing products for 12 hours prior to study visit days (except screening/randomization visit). c) Participants will abstain from strenuous exercise (e.g. heavy lifting, weight training, calisthenics, aerobics) for the duration of the study. Walking at a normal pace will be permitted.
  • A participant who has made use of prescription or non-prescription, NSAIDs, COX-2 inhibitors and dietary supplements within 7 days or 5 half-lives, whichever is longer, prior to the first dose of investigational product and during the study.
  • A participant with topical analgesics or anti-inflammatory treatment over the previous 30 days in the area to be treated in the study period.
  • A participant with evidence or history of clinically significant laboratory abnormality, hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease within the last 5 years that may increase the risk associated with study participation.
  • A participant with history of regular alcohol consumption exceeding 14 drinks per week (1 drink = 5 ounces [150 milliliter {mL}] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months of Screening.
  • A participant who has received treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product (whichever is longer).
  • A participant who has previously been enrolled in this study.
  • A participant with any physical impairment that would influence the study's efficacy evaluations, in particular POM and the ankle joint function, such as : peripheral or central neurological disease, significant back pain, symptomatic osteoarthritis of the hips, knees or feet, or any painful conditions of the lower extremities (e.g. painful nail, wound, corn, or wart).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04052620


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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China
GSK Investigational Site Not yet recruiting
Beijing, China, 101200
GSK Investigational Site Not yet recruiting
Chenzhou, China, 423000
GSK Investigational Site Not yet recruiting
Dalian, China, 116001
GSK Investigational Site Not yet recruiting
Kunming, China, 650032
GSK Investigational Site Not yet recruiting
Nanjing, China, 210001
GSK Investigational Site Not yet recruiting
Shanghai, China, 200025
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    877-379-3718    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site 2 Not yet recruiting
Shanghai, China, 200120
GSK Investigational Site Not yet recruiting
Shanghai, China, 200120
GSK Investigational Site Not yet recruiting
Shanghai, China, 201499
GSK Investigational Site Not yet recruiting
Shanghai, China, 201620
GSK Investigational Site Not yet recruiting
Shenyang, China, 110044
GSK Investigational Site Not yet recruiting
Shenzhen, China, 100730
GSK Investigational Site Not yet recruiting
Shenzhen, China, 518053
GSK Investigational Site Not yet recruiting
Shijiazhuang, China, 050051
GSK Investigational Site Not yet recruiting
Xi'an, China, 710061
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04052620     History of Changes
Other Study ID Numbers: 211206
2016L09875 ( Registry Identifier: NMPA )
First Posted: August 12, 2019    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: 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.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Ankle sprain
diclofenac diethylamine
Additional relevant MeSH terms:
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Diclofenac
Sprains and Strains
Ankle Injuries
Wounds and Injuries
Leg Injuries
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action