Pain
Conditions
Brief summary
The purpose of this study is to investigate how topical diclofenac use can improve functional mobility and physical activity primarily, as well as other quality-of-life (QoL) parameters such as sleep, mood, and engagement in daily activities in participants with knee OA.
Detailed description
This prospective open-label, single-arm, multi-country (United States \[US\] and European Union \[EU\]) real-world evidence study will be conducted in a hybrid form and will focus on assessing the impact of Voltaren Gel on functional mobility and QoL in individuals with mild/nonserious OA of the knee. Participants will be required to be physically present at the study site for screening, end of baseline and end of study visits. The remaining treatment will be conducted in a remote manner (for example, at home) to observe the real-world usage of Voltaren Gel. This study will utilize a research-grade validated wearable device: Actigraph, to accurately measure objective changes in functional mobility. Sufficient participants will be screened to enroll approximately 195 participants to ensure that around 147 of these participants will successfully complete the entire study.
Interventions
DRUGVoltaren Gel
Diclofenac sodium gel in 3 different concentrations as- Diclofenac sodium 1%, 1.16% and 2.32% whichever was available in the given region.
Sponsors
HALEON
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
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 is performed. * Participant is male or female who, at the time of screening, is between the ages of 40 and 85 years, inclusive. * A participant who is willing and able to comply with scheduled visits, on-label Voltaren Gel use plan, and other study procedures. * A participant willing to wear Actigraph continuously 24/7 for the study period. * A participant in good general and mental health. * A participant with diagnosed knee mild/non-serious osteoarthritis, proven via radiological evidence collected within the last 3 years. * A participant with self-reported knee pain, with a score of greater than or equal to (\>=) 40 millimeters (mm) less than or equal to (\<=)70mm on the pain intensity visual analogue scale at the time of Informed Consent Form (ICF) signature. * A participant willing to use Voltaren Gel for up to 3 weeks.
Exclusion criteria
* 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 Haleon employee directly involved in the conduct of the study or a member of their immediate family. * A participant who has participated in other studies (including non-medicinal studies) involving investigational product(s) within 1 month prior to study entry and/or during study participation. * A participant with, in the opinion of the investigator or medically qualified designee, an acute or chronic medical 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 with confirmed rheumatologic disease * A participant who has experienced trauma to the knee within the last 2 months that resulted in pain and/or swelling. * A participant that has been administered local steroids or other Non-steroidal anti-inflammatory drugs (NSAIDs) injections to the knee within the last 3 months. * A participant with recent history of major knee injury or surgery. * A participant with knee skin area pathological condition which prevents application of product to the skins. Conditions such as: open skin wounds, infections, inflammations, or exfoliative dermatitis conditions. * A participant with conditions not limited to the following: Gastrointestinal diseases, asthma, hypertension, myocardial infarction, thrombotic events, stroke, congestive heart failure, impaired renal function, or liver disease as judged by investigator or Site Staff. * A participant diagnosed with other relevant medical conditions (example, psychiatric, neurological). * A participant who takes medication relating to above conditions, such as tricyclic antidepressants or anticonvulsants. * A participant with an active infection. * A participant who is pregnant, lactating, or plan to be pregnant or lactating during the study. * A participant with use of aspirin, Oral NSAIDs, topical treatment with any NSAIDs, warfarin, Angiotensin-converting enzyme (ACE) inhibitors, cyclosporine, diuretics, lithium or methotrexate, corticosteroids, or other anticoagulant therapy within 30 days of study. * A participant with known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients, including hypersensitivity to NSAIDs and aspirin triad. * A participant with any other acute or chronic illness that could compromise the integrity of study data or place the participant at risk by participating in the study. * A participant who, in the opinion of the investigator or medically qualified designee, should not participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average Minutes of Moderate and Vigorous Physical Activity (MVPA) at Week 1 | Baseline and Week 1 | The average minutes of MVPA were measured through a connected activity tracker (Actigraph device) worn by the participants to evaluate the effects of Voltaren Gel on physical activity. A mixed model with repeated measures (MMRM) was used to analyse the change from Baseline in MVPA average minutes. Change from Baseline was calculated by subtracting the Baseline average MVPA value from the average MVPA value at Week 1. Baseline value was calculated as the sum of minutes of MVPA over the Baseline period divided by duration of Baseline period, where Baseline period was the number of non-missing days between Day -6 and Day 0. A positive change from Baseline indicated improvement. Modified Intent-To-Treat (mITT) population included all participants who met the inclusion/exclusion criteria, who used study product at least once and had data from at least one post Baseline quality of life (QoL) questionnaire to support at least one of the secondary endpoint assessments. |
| Change From Baseline in the Average Minutes of MVPA at Week 2 | Baseline and Week 2 | The average minutes of MVPA were measured through a connected activity tracker (Actigraph device) worn by the participants to evaluate the effects of Voltaren Gel on physical activity. A MMRM was used to analyse the change from Baseline in MVPA average minutes. Change from Baseline was calculated by subtracting the Baseline average MVPA value from the average MVPA value at Week 2. Baseline value was calculated as sum of minutes of MVPA over the Baseline period divided by duration of Baseline period, where Baseline period was the number of non-missing days between Day -6 and Day 0. A positive change from Baseline indicated improvement. |
| Change From Baseline in the Average Minutes of MVPA at Week 3 | Baseline and Week 3 | The average minutes of MVPA were measured through a connected activity tracker (Actigraph device) worn by the participants to evaluate the effects of Voltaren Gel on physical activity. A MMRM was used to analyse the change from Baseline in MVPA average minutes. Change from Baseline was calculated by subtracting the Baseline average MVPA value from the average MVPA value at Week 3. Baseline value was calculated as sum of minutes of MVPA over the Baseline period divided by duration of Baseline period, where Baseline period was the number of non-missing days between Day -6 and Day 0. A positive change from Baseline indicated improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Daily Average Number of Steps Taken at Weeks 1, 2 and 3 | Baseline, Week 1, Week 2 and Week 3 | Daily average number of steps taken were measured through a connected activity tracker (Actigraph device) worn by the participants to evaluate the effects of Voltaren Gel on functional mobility. MMRM was used to analyse the change from Baseline in daily average number of steps taken. Change from Baseline was calculated by subtracting the average number of steps taken at Baseline from the average number of steps taken at each indicated post-Baseline timepoint. Baseline value was calculated as the sum of steps taken over the Baseline period divided by duration of Baseline period, where Baseline period was the number of non-missing days between Day -6 and Day 0. A positive change from Baseline indicated improvement. |
| Change From Baseline in Ratio of Sedentary/Non-sedentary Time at Weeks 1, 2 and 3 | Baseline, Week 1, Week 2 and Week 3 | Sedentary/non-sedentary time was measured using a connected activity tracker (Actigraph device) worn by the participants to evaluate the effects of Voltaren Gel on functional mobility. Ratio of sedentary/non-sedentary time was calculated as = Total number of minutes defined as sedentary behaviour divided by Total number of non-sedentary behaviour minutes where number of non-sedentary behaviour minutes in the day was derived as the sum of light activity and MVPA. Change from Baseline was calculated by subtracting the Baseline ratio of sedentary/non-sedentary time from the ratio at each indicated post-Baseline timepoint. Baseline was defined as the number of non-missing days between Day -6 and Day 0. A negative change from Baseline indicated improvement. |
| Change From Baseline in Gait Assessed Through Speed and Step Irregularity Measured Via Cadence at Weeks 1, 2 and 3 | Baseline, Week 1, Week 2 and Week 3 | Gait was assessed through speed and step irregularity measured via cadence using a connected activity tracker (Actigraph device) worn by the participants. Change from Baseline was calculated as by subtracting the average cadence at Baseline from the cadence at each indicated post-Baseline timepoint. Baseline was defined as the number of non-missing days between Day -6 and Day 0. A positive change from Baseline indicated improvement. |
| Change From Baseline in Gait Assessed Through Speed and Step Irregularity Measured Via Gait Speed at Weeks 1, 2 and 3 | Baseline, Week 1, Week 2 and Week 3 | Gait was assessed through speed and step irregularity measured via gait speed using a connected activity tracker (Actigraph device) worn by the participants. Change from Baseline was calculated by subtracting the average gait speed at Baseline from the Average gait speed at each indicated post-Baseline timepoint. Baseline was defined as the number of non-missing days between Day -6 and Day 0. A positive change from Baseline indicated improvement. |
| Change From Baseline in Indices of Morning Stiffness Assessed Through Levels of Mobility 30 Minutes Post-wake at Weeks 1, 2 and 3 | Baseline, Week 1, Week 2 and Week 3 | Indices of morning stiffness were assessed through levels of mobility 30 minutes post-wake. Functional mobility was measured through a connected activity tracker (Actigraph device) worn by the participants. Daily morning stiffness 30 minutes post-wake was defined as the total vector magnitude counts from Actigraph device 30 minutes post-wake. Change from Baseline was calculated as = (Average morning stiffness 30 minutes post-wake at each indicated post-Baseline timepoint minus Average Baseline morning stiffness 30 minutes post-wake). Baseline was defined as the number of non-missing days between Day -6 and Day 0. A negative change from Baseline indicated improvement. |
| Change From Baseline in Indices of Morning Stiffness Assessed Through Levels of Mobility 60 Minutes Post-wake at Weeks 1, 2 and 3 | Baseline, Week 1, Week 2 and Week 3 | Indices of morning stiffness were assessed through levels of mobility 60 minutes post-wake. Functional mobility was measured through a connected activity tracker (Actigraph device) worn by the participants. Daily morning stiffness 60 minutes post-wake was defined as the total vector magnitude counts from Actigraph device 60 minutes post-wake. Change from Baseline was calculated as = (Average morning stiffness 60 minutes post-wake at each indicated post-Baseline timepoint minus Average Baseline morning stiffness 30 minutes post-wake). Baseline was defined as the number of non-missing days between Day -6 and Day 0. A negative change from Baseline indicated improvement. |
| Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Physical Function Subscale Score at Week 1, 2 and 3 | Baseline, Week 1, Week 2 and Week 3 | Participants completed the WOMAC questionnaire daily using eDiary. The WOMAC questionnaire consisted of 24 questions categorised in 3 subscales - Pain, Stiffness, Physical function. The physical function subscale consisted of 17 questions related to level of difficulty in performing functions, on average, during the last 48 hours scored on a 5-point Likert scale with scores ranging from 0 to 4, where score 0=none, 1=slight, 2=moderate, 3=severe, 4=extreme. Total WOMAC physical function subscale score was normalized on a 0 to 100 scale calculated as = (sum of raw score items)\*1.47. Higher scores indicated more difficulty in performing physical functions. Change from Baseline was calculated by subtracting the normalized WOMAC subscale score at Baseline from the normalized WOMAC subscale score at each indicated post-Baseline timepoint. Baseline was defined as Day 0. A negative change from Baseline indicated improvement. |
| MVPA on Each Day of the Study | Baseline up to Day 21 | The average minutes of MVPA on each day were measured through a connected activity tracker (Actigraph device) worn by the participants to assess the functional mobility. Baseline was calculated as the average of MVPA values collected during the Baseline period, where Baseline period was the number of non-missing days between Day -6 and Day 0. |
| WOMAC Physical Function Subscale Score at Weeks 1, 2 and 3 | Week 1, Week 2 and Week 3 | Physical function subscale score of the WOMAC questionnaire was used to study participant's perceived ability to exercise more regularly. It consisted of 17 questions related to the level of difficulty in performing functions, on average, during the last 48 hours scored on a 5-point Likert scale with scores ranging from 0 to 4, daily using eDiary where score 0=none, 1=slight, 2=moderate, 3=severe, 4=extreme. Total WOMAC physical function subscale score was normalized on a 0 to 100 scale calculated as = (sum of raw score items)\*1.47. Higher scores indicated more difficulty in performing physical functions. |
| Change From Baseline in Self-reported Pain Intensity Assessed Through Numeric Rating Scale (NRS) at Weeks 1, 2 and 3 | Baseline, Week 1, Week 2 and Week 3 | Participants rated the pain intensity experienced by them daily within the eDiary, using NRS. NRS is an 11-point scale with scores ranging from 0 to 10 where score 0 = no pain, 1 = slight pain, 2-3 = mild pain, 4-6 = moderate pain, 7 = severe pain, 8 to 9 = extreme pain, 10=pain as bad as it could be. Higher scores indicated greater pain intensity. Change from Baseline was calculated by subtracting the Baseline NRS score from the NRS score at each indicated post-Baseline timepoint. Baseline was defined as Day 0. A negative change from Baseline indicated improvement. |
| Change From Baseline in the WOMAC Total Score at Weeks 1, 2 and 3 | Baseline, Week 1, Week 2 and Week 3 | Participants completed the WOMAC questionnaire daily. The WOMAC questionnaire consisted of 24 questions each scored on a 5-point scale: 0=none, 1=slight, 2=moderate, 3=severe, 4=extreme. The WOMAC questionnaire was categorized in 3 subscales - Pain (5 questions, score ranges 0-20), Stiffness (2 questions, score ranges 0-8), Physical function (17 questions, score ranges 0-68). Each subscale score was normalized on a 0 to 100 scale calculated as: Pain subscale score= (sum of raw score items in dimension)\*5; Stiffness subscale score= (sum of raw score items in dimension)\*12.5; Physical function subscale score= (sum of raw score items in dimension)\*1.47. WOMAC Total score = sum of the 3 normalized WOMAC subscale scores. Thus, WOMAC total score ranges from 0 to 300 with 0 being the best and 300 being the worst. Change from Baseline was calculated by subtracting the Baseline score from score at each indicated post-Baseline timepoint. A negative change from Baseline indicated improvement. |
| Change From Baseline in the WOMAC Pain Subscale Score at Weeks 1, 2 and 3 | Baseline, Week 1, Week 2 and Week 3 | The pain subscale of the WOMAC questionnaire consisted of 5 questions related to severity of pain experienced by the participant when walking, stair climbing, at night, at rest, weightbearing, on average, during the last 48 hours. Participants scored the questions on a 5-point Likert scale ranging from 0 to 4 daily using eDiary where score 0=none, 1=slight, 2=moderate, 3=severe, 4=extreme. The total pain subscale score was normalized on a 0 to 100 scale calculated as = (sum of raw score items in dimension)\*5. Higher scores indicated more pain. Change from Baseline was calculated by subtracting the Baseline normalized WOMAC pain subscale score from the normalized score at each indicated post-Baseline timepoint. Baseline was defined as Day 0. A negative change from Baseline indicated improvement. |
| Change From Baseline in the WOMAC Stiffness Subscale Score at Weeks 1, 2 and 3 | Baseline, Week 1, Week 2 and Week 3 | The stiffness subscale of the WOMAC questionnaire consisted of 2 questions related to severity of stiffness experienced by the participant at morning and during the day, on average, during the last 48 hours. Participants scored the questions on a 5-point Likert scale with scores ranging from 0 to 4 daily using eDiary, where score 0=none, 1=slight, 2=moderate, 3=severe, 4=extreme. The total stiffness subscale score for was normalized on a 0 to 100 scale calculated as = (sum of raw score items in dimension)\*12.5. Higher scores indicated more stiffness. Change from Baseline was calculated by subtracting the Baseline normalized WOMAC stiffness subscale score from the normalized score at each indicated post-Baseline timepoint. Baseline was defined as Day 0. A negative change from Baseline indicated improvement. |
| Change From Baseline in Sleep/Alertness Assessed Using Karolinska Sleepiness Scale (KSS) at Days 7, 14 and 21 | Baseline, Day 7, Day 14, and Day 21 | KSS measured the subjective level of sleepiness/alertness during the day. Participants rated how sleepy or alert they were feeling using KSS with scores ranging from 1 to 9 where 1 = extremely alert, 2 = very alert, 3 = alert, 4 = fairly alert, 5 = neither alert nor sleepy, 6 = some signs of sleepiness, 7 = sleepy, but no efforts to keep alert, 8 = sleepy, some efforts to keep alert, 9 = very sleepy, great effort to keep alert, fighting sleep. Higher scores indicated greater sleepiness. Change from Baseline was calculated by subtracting the Baseline score from score at each indicated post-Baseline timepoint. Baseline was defined as Day 0. A negative change from Baseline indicated improvement. |
| Change From Baseline in Health-related QoL Assessed Using EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire at Days 7, 14, and 21 | Baseline, Days 7, 14 and 21 | Health-related QoL of participants was assessed using the EQ-5D-5L questionnaire. It consisted of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) with 5 response levels for each dimension where Level 1 = no problems, Level 2 = slight problems, Level 3 = moderate problems, Level 4 = severe problems, Level 5 = unable to perform activities/extreme problems. Participants were asked to indicate their health by ticking the box next to the most appropriate response level for each dimension. The response levels were used to derive a health index score based on the Crosswalk Value Set for the United States ranging from less than 0 (worst imaginable health) to 1 (best imaginable health) where higher scores indicated better health. Change from Baseline was calculated by subtracting the Baseline score from score at each indicated timepoint. Baseline was defined as Day 0. A positive change from Baseline indicated improvement. |
Countries
Poland, United States
Participant flow
Recruitment details
This study was conducted at 2 centers in the United States (US) and 6 centers in the European Union (EU) (Poland).
Pre-assignment details
A total of 214 participants were screened during study of which 196 participants were enrolled and received Voltaren Gel. A total of 194 participants completed the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 9.33 |
| Race/Ethnicity, Customized Hispanic or Latino | 19 Participants |
| Race/Ethnicity, Customized Missing | 157 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 188 Participants |
| Sex: Female, Male Female | 118 Participants |
| Sex: Female, Male Male | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 196 |
| other Total, other adverse events | 17 / 196 |
| serious Total, serious adverse events | 0 / 196 |
Outcome results
None listed