GlucoRx Allpresan diabetic foam creams

Transcription

1 GlucoRx Allpresan diabetic foam creams This document is for use with decision makers within the NHS. Its aim is to make such individuals aware of the evidence to support the use of GlucoRx Allpresan diabetic foam creams in the UK. Further information is available from the GlucoRx Head Office. Tel:

2 PRESCRIBING INFORMATION CAN BE FOUND IN APPENDIX 1 Contents Summary... 3 Background... 5 Dry skin... 5 Foot ulcers... 6 Guidance... 6 NICE Guidance... 6 SIGN Guidance... 6 Unmet need... 6 Foam creams... 7 Application... 7 Patient acceptance and ease of use... 7 Dispensing... 7 Place in therapy... 7 GlucoRx Allpresan... 8 Indication Mechanism of action... 8 Medical device... 8 Clinical evidence... 8 Study by Baker et al... 8 Study by Wigger-Alberti et al... 9 Study by Proksch Study by Bristow Budget impact Appendix 1: Prescribing Information GlucoRx Allpresan diabetic Foam Cream BASIC GlucoRx Allpresan diabetic Foam Cream INTENSIVE References

3 Summary Background Treating dry skin is a key element of preventing foot ulcers in people with diabetes. 1,2 Diabetes mellitus is among the most common conditions in the UK, with 3.5 million people in the UK diagnosed with diabetes in Up to 80% of people with diabetes suffer from dry skin, which is more vulnerable to breakdown 2,4 Dry skin on a diabetic foot is one of the risk factors for foot ulcer formation. 1 About 10% of people with diabetes will have a foot ulcer at some point in their lives 5 Diabetes is the most common cause of non-traumatic limb amputation, with diabetic foot ulcers preceding more than 80% of amputations in people with diabetes. 5 There are over 135 amputations a week among people with diabetes 3 Guidance NICE recommends that there is a foot protection service for preventing diabetic foot problems, and for treating and managing diabetic foot problems in the community. For adults with diabetes, their risk of developing a diabetic foot problem should be assessed when diabetes is diagnosed and at least annually thereafter; if any foot problems arise; and on any admission to hospital. For people at moderate or high risk of developing a diabetic foot problem, the foot protection service must give advice about, and provide, skin and nail care of the feet 5 SIGN recommends that all patients with diabetes should be screened at least annually to assess their risk of developing a foot ulcer and those with active diabetic foot disease should be referred to a multidisciplinary diabetic foot service team 6 Unmet need Emollient creams should not be applied between the toes. 7 Treating dry skin with foam creams help stabilise the epidermal barrier and improve symptoms 8 Dry skin on a diabetic foot has traditionally been treated with an emollient 9 Conventional creams should not be applied between the toes because this can cause the skin to become too moist and lead to an infection developing 10 Daily application of foot moisturisers by people with diabetes may stop after 2-3 weeks of commencement, due to a perceived lack of skin moisturising effect 11 Foam creams GlucoRx Allpresan diabetic foam creams can be spread evenly, including into the spaces between toes. 12 The foam creams are convenient and easy for patients to use, especially those who may have mobility problems. 8 The foam cream is readily absorbed, can be spread easily and is not sticky 8 The foam creams are dispensed from a spray can in a clean and hygienic way, allowing for small dosages and protection of the product from contamination, which is advantageous over creams dispensed from a tube, pot or pump dispenser 12 Place in therapy GlucoRx Allpresan diabetic foam cream is the only clinically formulated foam cream to prevent dry cracked skin and calluses on diabetic feet. GlucoRx Allpresan diabetic foam cream boosts the skin s barrier function, thus protecting against skin infections and ulceration It is the only foam cream to be clinically approved in the UK for use on the entire foot including between the toes 12,14,16 3

4 GlucoRx Allpresan diabetic foam cream is quick to apply, non-greasy and footwear can be put on immediately after application 13 Indication GlucoRx Allpresan diabetic foam cream BASIC (5% urea) is a medical device for the specific treatment of dry and sensitive foot skin in patients with diabetes mellitus 14 GlucoRx Allpresan diabetic foam cream INTENSIVE (10% urea) is a medical device for the specific treatment for very dry to chapped foot skin in patients with diabetes mellitus 16 Mechanism of action GlucoRx Allpresan diabetic foam creams contains a unique complex of moisturising agents: pentavitin, panthenol and urea. 14,16 Pentavitin is a moisturiser which contains naturally-occurring carbohydrates. Pentavitin binds strongly to the skin and has a highly-effective moisture-regulating capability 17 Panthenol acts as a moisturiser, improving stratum corneum hydration, reducing transepidermal water loss and maintaining skin softness and elasticity 18 Urea is a keratin softener and hydrating agent used in the treatment of dry, scaling conditions. 19 Urea increases the moisture content of the keratinous layer of the skin, making the skin softer and more supple, as well as relieving itchiness 16 When the foam is applied, it forms a two-dimensional protective mesh on the skin, so the skin is able to breathe and is protected from external influences 14,16 Medical device GlucoRx Allpresan diabetic foam creams are class IIa medical devices. 20 A medical device is used for the prevention, treatment or alleviation of disease and its main action is not pharmacological 21 Clinical data for a medical device means the safety and/or performance generated from the use of the device. Clinical data are sourced from clinical investigation of the actual medical device or a similar, equivalent medical device 21 Clinical evidence Baker et al examined the effects of GlucoRx Allpresan-3, containing 10% urea in 26 patients with diabetes and dry skin on both feet. GlucoRx Allpresan-3 does not contain the moisturising complex of pentavitin, panthenol and urea but it was still considered superior to the control moisturisers in terms of application, absorption, rehydration and overall effectiveness by the majority of patients. More than 83% of participants rated GlucoRx Allpresan-3 high for ease of application, absorption, postapplication skin feel, improved skin hydration and overall satisfaction. Most (96%) participants preferred and wished to continue using GlucoRx Allpresan-3 over their control moisturiser. 11 Wigger-Alberti et al evaluated the effects of GlucoRx Allpresan diabetic foam cream intensive in patients with diabetes and dry/sensitive skin and compared with two other GlucoRx Allpresan foam creams. 13 After twice daily application for 4 weeks, both dermatological and subjective assessments showed an improvement in symptoms, with many symptoms improving after 1 week of use The foam cream formulations showed a moisturising effect while no clinically significant increase of bacterial colonisation was observed in the interdigital area of the foot All three products were well accepted by the patients, with 80% preferring a foam cream to a conventional lotion or cream and 85% of them more willing to carry out daily foot care with a foam cream The majority of patients (>90%) assessed the improvement in their skin condition as very good or good and 80% preferred how the foam cream was applied and absorbed to that of a conventional lotion or cream Over 95% perceived the risk of slipping to be moderate to negligible 4

5 Proksch carried out a study in 20 patients with diabetes with GlucoRx Allpresan diabetic foam cream Intensive. 22 Skin hydration on the forearm increased by 32.2% after 14 days and by 38.7% after 28 days, and by 47.6% and 49.5% respectively on the foot/ankle Skin smoothness was significantly increased on the test areas (p<0.05), increasing by 9.7% after 14 days and by 17.5% after 28 days on the forearm After both 14 and 28 days of treatment, a significant (p<0.05) improvement in satisfaction with the skin condition and in experienced pruritus was seen with respect to the evaluated treatment area In a 14-day patient and podiatrist evaluation study, GlucoRx Allpresan diabetic foam cream INTENSIVE (10% urea) applied to one foot (test foot was found to be as effective as a non-foaming 10% urea cream applied to the other foot (control foot) (n=20 patients with dry feet/heels). 23 At day 14, there was a significant reduction in overall dryness scores for both feet in all patients (p<0.000 for changes in mean dryness scores from baseline in each foot). Efficacy of the test product was rated by clinicians as good (35%) to excellent (45%) and tolerability as good (15%) to excellent (85%) in all participants 23 Patient evaluations showed overall a high level of satisfaction with the product, showing overall agreement with the benefits of the test product 23 Participating podiatrists felt that a foam cream promoted less wastage and that owing to the texture and application of the foam, GlucoRx Allpresan foam cream could make an excellent postoperative application to be kept in the surgery for patients following podiatry treatment, as it is clean and quick to apply and didn t need to be worked in as much as creams, saving practitioners time at the end of a consultation 23 Budget impact People using GlucoRx Allpresan diabetic foam cream INTENSIVE (10% urea) required only 0.11g of product to cover the same area covered by 0.24g of a non-foaming 10% urea emulsion. 24 Less than half the amount of GlucoRx Allpresan diabetic foam cream INTENSIVE is needed per application compared with a non-foaming 10% urea emulsion. 16,24 In another study in 20 subjects, on average, 35mL of GlucoRx Allpresan diabetic foam cream INTENSIVE was 23 required for two weeks worth of treatment. Background Diabetes mellitus is among the most common chronic conditions in the UK and its prevalence is increasing. 25,5 In 2014, there were 3.5 million people in the UK diagnosed with diabetes, and by 2025, it is estimated that 5 million people will have diabetes in the UK. 3 The majority of people with diabetes have type 2 diabetes (90%). 3 Dry skin If skin is abnormally dry, fissures can develop, the skin loses its elasticity and flexibility and ability to withstand trauma, resulting in skin breakdown and subsequent infection. 26 Treating dry skin is a key element of preventing skin breakdown and foot ulcers in people with diabetes. 1,27 A healthy skin barrier is crucial to protect against mechanical, microbial and chemical damage. 8 Up to 80% of people with diabetes suffer from dry skin. 4,8 In people with diabetes, neuropathy causes decreased sweating and the lipid matrix of the skin is altered; these can result in deterioration of the epidermal protective function, which manifests as an impaired stratum corneum (the outermost layer of the epidermis), or dry skin, as well as scaling and pruritus. 2,8,12 This makes the skin more vulnerable to breakdown. 2 Dry skin on a diabetic foot is one of the risk factors for foot ulcer formation. 1 5

6 Foot ulcers About 10% of people with diabetes will have a diabetic foot ulcer at some point in their lives. 5 Foot ulceration usually precedes lower limb amputation, due to a combination of nerve damage (neuropathy), which reduces sensation in the lower limbs and feet, and impaired circulation. 2,3,7 Diabetic foot ulcers precede more than 80% of amputations in people with diabetes. 5 There are over 100 amputations a week among people with diabetes. 3 Ulceration and amputation reduce quality of life and are associated with increased mortality. 28 Foot ulcers are painful and require considerable time spent on clinic visits, hospitalisation and wound dressing changes. 28 Amputations can result in long-term changes to mobility, living conditions and relationships. 28 People with diabetes are also susceptible to foot infections, mainly because of neuropathy, poor circulation and reduced neutrophil function. 5,29 Once the skin is broken, the infection can spread rapidly to underlying tissues, causing extensive tissue destruction and direct threat to the affected limb. 7,28,29 Infection is the main reason for major amputation in neuropathic feet and a frequent cause of amputation in ischaemic and neuro-ischaemic feet. 28 Guidance NICE Guidance NICE state that a foot protection service for preventing diabetic foot problems, and for treating and managing diabetic foot problems in the community should be in place. There should also be a multidisciplinary foot care service for managing diabetic foot problems in hospital and in the community that cannot be managed by the foot protection service. 5 For adults with diabetes, their risk of developing a diabetic foot problem should be assessed: when diabetes is diagnosed and at least annually thereafter; if any foot problems arise; and on any admission to hospital, and if there is any change in their status while they are in hospital. 5 When examining the feet of a person with diabetes, their shoes, socks, bandages and dressings must be removed and both feet examined for any signs of the following risk factors: neuropathy, limb ischaemia, ulceration, callus, infection and/or inflammation, deformity, gangrene, Charcot arthropathy. A patient at low risk of developing a diabetic foot problem or needing an amputation indicates no risk factors present; moderate risk indicates one risk factor present and high risk indicates previous ulceration or amputation, on renal replacement therapy or more than one risk factor present. 5 For people at moderate or high risk of developing a diabetic foot problem, the foot protection service must give advice about, and provide, skin and nail care of the feet. Information should be oral and written and include basic foot care advice and the importance of foot care. 5 The Quality and Outcome Framework (England) contains the following indicator for diabetes: 30 DM012. The percentage of patients with diabetes, on the register, with a record of a foot examination and risk classification: 1) low risk (normal sensation, palpable pulses), 2) increased risk (neuropathy or absent pulses), 3) high risk (neuropathy or absent pulses plus deformity or skin changes in previous ulcer) or 4) ulcerated foot within the preceding 12 months SIGN Guidance All patients with diabetes should be screened at least annually to assess their risk of developing a foot ulcer. 6 Those with active diabetic foot disease should be referred to a multidisciplinary diabetic foot service team. 6 Unmet need Dry skin on a diabetic foot makes it vulnerable to breakdown and ulcer formation; this can be complicated by infections. 2,26 Microvascular disease can cause poor blood circulation to the skin and can slow down healing of broken skin. 31 6

7 Intensive daily foot care must include an appropriate regime to replenish the skin s moisture and fat content and create a protective layer against the outside environment. Dry skin on a diabetic foot has traditionally been treated with an emollient, but conventional creams should not be applied between the toes because this can cause the skin to become too moist and lead to an infection developing. 7,9,10 Adherence to daily application of moisturisers is often short-lived among people with diabetes, with treatment stopping 2-3 weeks after starting due to a perceived lack of skin moisturising effect. 11 Effective skin care needs to supply moisture and lipids and restore the epidermal protective function. 12 The ideal skin-care product would lead to a gradual increase in hydration over a period of time and a decrease in trans-epidermal water loss. 12 GlucoRx Allpresan diabetic foam creams are specifically formulated to treat dry and very dry diabetic skin and can be used to cover and protect the entire foot, from heel to toe, including between the toes. 12,14,16 Foam creams Treating dry skin with GlucoRx Allpresan diabetic foam creams help stabilise the epidermal barrier and improve symptoms. 8 The water content of the foam cream evaporates from the skin surface, converting the product into a lipophilic form, resulting in a higher concentration of the active substance, urea, and better absorption through the skin. 12 The foam character is not lost during the drying process: microscopic foam bubbles are present 30 minutes after application and drying, implying that no occluding cream layer is formed and that trans-epidermal water exchange between the epidermis and the environment is maintained. 12 GlucoRx Allpresan diabetic foam creams can be applied to and will protect the entire foot, from heel to toe, including between the toes. 12,14,16 Application GlucoRx Allpresan diabetic foam creams are easy to apply and can be spread evenly, including into difficult-toreach sites such as the spaces between toes. 12 They are convenient and easy for patients to use, especially those who may have mobility problems. 8 The foam cream is readily absorbed, can be spread easily and is not sticky or greasy. 8,14,16 Patient acceptance and ease of use Despite the treatment of dry skin being a key element to preventing foot ulcers and infection, it is often neglected. 1 Patients complain that emollients make their feet slippery and they do not want to slip or fall, or that they make their footwear dirty. 1 In a four-week study assessing ease of use of foam creams, 85% of 92 people with diabetes confirmed that the foam cream was rapidly and completely absorbed and 82.5% reported that they could put on their socks without any problems immediately after applying the foam cream. 1 Dispensing GlucoRx Allpresan diabetic foam creams are dispensed from a spray can in a clean and hygienic way, allowing for small dosages and protection of the product from contamination, which is advantageous over creams dispensed from a tube. The foam develops as soon as the emulsion is ejected out of the aerosol nozzle. No preservatives are needed and sensitive ingredients are protected by the airtight packaging. 12 Place in therapy GlucoRx Allpresan diabetic foam cream is formulated to prevent dry cracked skin and calluses on diabetic feet. GlucoRx Allpresan diabetic foam creams are the only products to be clinically approved in the UK for use on the entire diabetic foot including between the toes. 12,14,16 GlucoRx Allpresan diabetic foam cream boosts the skin s barrier function, thus protecting against skin infections and ulceration GlucoRx Allpresan diabetic foam cream forms a breathable protective coating with a specific formula that strengthens and repairs the skin barrier. 14,16 GlucoRx Allpresan diabetic foam cream is quick to apply, nongreasy and footwear can be put on immediately after application. 13 7

8 GlucoRx Allpresan Indication GlucoRx Allpresan diabetic foam cream BASIC (5% urea) is a medical device for the specific treatment of dry and sensitive foot skin in patients with diabetes mellitus. GlucoRx Allpresan diabetic foam cream Basic reduces roughness, counteracts pressure marks and smoothes the skin. 14 GlucoRx Allpresan diabetic foam cream INTENSIVE (10% urea) is a medical device for the specific treatment for very dry to chapped foot skin in patients with diabetes mellitus. GlucoRx Allpresan diabetic foam cream INTENSIVE counteracts pressure marks and helps prevent calluses. 16 Both GlucoRx Allpresan diabetic foam creams can be used on the entire foot, from heel to toe, including between the toes and around wound edges. 12,14,16 Only a small amount is required, about the size of a hazelnut or walnut depending on the size of the area to be treated. The foam cream is easy to rub in and can be applied quickly without leaving behind a greasy film. Footwear can be put on immediately after use. 14,16 Mechanism of action GlucoRx Allpresan diabetic foam creams contains a unique complex of moisturising agents: pentavitin, panthenol and urea. 14,16 When the foam is applied, it forms a two-dimensional protective mesh on the skin, so the skin is able to breathe and is protected from external influences. 14,16 GlucoRx Allpresan diabetic foam cream boosts the skin s barrier function, thus protecting against skin infections and ulceration Pentavitin is a moisturiser which contains naturally occurring carbohydrates, similar to those found in the stratum corneum of skin. 17 Pentavitin binds strongly to the skin and cannot be washed off easily, so moisture remains in the skin, protecting against dehydration. 16,17 Pentavitin is removed by natural skin shedding. It has a highly effective moisture-regulating capability, with long-lasting moisture-binding and moisture retention 17 Panthenol acts as a moisturiser, improving stratum corneum hydration, reducing transepidermal water loss and maintaining skin softness and elasticity. Promotion of regeneration of the skin barrier, which is necessary for wound healing, has been observed with panthenol 18 Urea is a keratin softener and hydrating agent used in the treatment of dry, scaling conditions. 19 Urea is also used as a proteolytic agent for wound debridement. 32 The hydrating properties of urea, used in concentrations up to 10%, offer clinical benefits to people with dry skin. 32 It increases the moisture content of the keratinous layer of the skin, making the skin softer and more supple, as well as relieving itchiness. 16 Trans-epidermal water loss, used to assess skin hydration, is reduced by urea used on both dry and healthy skin 32 Medical device GlucoRx Allpresan diabetic foam creams are class IIa medical devices. 20 A medical device is used for the prevention, treatment or alleviation of disease and does not achieve its main action by pharmacological activity, but may be assisted in its function by such means. 21 Clinical data for a medical device means the safety and/or performance generated from the use of the device. 21 Clinical data are sourced from clinical investigation of the actual medical device or a similar, equivalent medical device or published/unpublished reports on other clinical experience of either the device in question or a similar device for which equivalence can be demonstrated. 21 There are a number of clinical trials which support the use of GlucoRx Allpresan diabetic foam cream. 11,13,22 Clinical evidence Study by Baker et al A pilot study carried out in the UK examined the effects of GlucoRx Allpresan-3 foam cream, containing 10% urea, in 26 patients with diabetes with dry skin on both feet and neuropathy. Three clinical parameters were measured at baseline and endpoint: (1) skin dryness, (2) skin flexibility and (3) callus formation, as well as patient satisfaction. 8

9 The clinical parameters were assessed on a five-point scale, where 1 = normal, supple plantar skin without dryness or callus and 5 = extremely dry, very inflexible plantar skin with thick callus. All participants were asked to apply GlucoRx Allpresan-3 to the allocated test foot, and their regular moisturising cream to the contra-lateral non-test foot. Each moisturiser (test and control) was to be applied to its assigned foot, over the whole surface, but not between the toes, twice daily for 2 weeks. The control moisturisers were aqueous cream, E45 cream, Diprobase and Unguentum Merck. 11 For both skin dryness and skin flexibility, GlucoRx Allpresan 3 was shown to be significantly more effective than the control moisturisers by the end of the 2-week study period (p= for both parameters, Table 1). For callus formation, there was a small reduction seen with GlucoRx Allpresan- 3 compared with the control moisturisers, although it was not statistically significant. 11 Table 1: Mean scores for each of the clinical parameters tested 11 GlucoRx Allpresan-3 Control moisturiser Baseline Week 2 Score difference Baseline Week 2 Score difference Skin dryness Skin flexibility Callus formation GlucoRx Allpresan-3 does not contain the moisturising complex of urea, pentavitin and panthenol but it was still considered superior to the control moisturisers in terms of application, absorption, rehydration and overall effectiveness by the majority of patients. More than 83% of participants rated GlucoRx Allpresan-3 high for ease of application, absorption, post-application skin feel, improved skin hydration and overall satisfaction. Most (96%) participants preferred and wished to continue using GlucoRx Allpresan-3 over their control moisturiser. 11 Study by Wigger-Alberti et al The skin-moisturising properties and potential application in the interdigital spaces of three foam creams was tested in 60 patients with type 1 or type 2 diabetes. Patients applied one of three foam creams twice a day for 29 days to their feet, including the interdigital area: GlucoRx Allpresan diabetic Intensive (n=20), GlucoRx Allpresan diabetic Intensive Care with microsilver (n=20) and GlucoRx Allpresan diabetic Intensive Care with polyhexanide (n=20). 13 Patients Two-thirds (66.7%) of patients enrolled were female, and the overall mean age was 58.8 years. 13 Assessments Interdigital swabs were taken and skin humidity was assessed by corneometry on day 1. Swabs were taken from the interdigital spaces between toes 1 and 2 and between toes 3 and 4. Clinical and subjective assessments and measurements of skin humidity were conducted on days 8, 15 and 29, and interdigital swabs taken on day Dermatological assessments were skin redness, dryness, desquamation, cracking, oedema, papules, blisters, oozing skin areas, and skin erosions. Subjective assessments were made on a 4-point scale ranging from not perceived to very strongly perceived for itching, stinging, burning sensation, dryness and tightness. 13 Results Bacterial counts Application of the foam cream between the interdigital spaces did not increase gram-positive bacteria. The bacterial colonisation had an absolute log 10 value of 4.6 before treatment with GlucoRx Allpresan diabetic Intensive and 4.8 after 29 days. Results for all three groups are shown in figure 1. The colonisation of the interdigital spaces with gram-negative bacteria was nearly zero both before the start of the application (day 1) and after completion of the study (day 29). 13 9

10 Figure 1: Mean colonisation of the interdigital spaces with gram-positive bacteria before (day 1) and after 4 weeks of application (day 29) 13 Adapted from Wigger-Alberti W et al. Cosmet Med 2015;1(15): Corneometry Corneometry measurements indicated an increase in skin moisture after 8 days in relation to day 1, which was maintained to day 29 (Table 2 and Figure 2). 13 Table 2: Mean corneometry measurements 13 GlucoRx Allpresan diabetic Intensive GlucoRx Allpresan diabetic Intensive Care with microsilver GlucoRx Allpresan diabetic Intensive Care with polyhexanide Day a.u a.u a.u. Day a.u a.u a.u. Day a.u a.u a.u. Day a.u a.u a.u. 10

11 Figure 2: Development of moisture content in the stratum corneum in relation to the application of different foam creams 13 Adapted from Wigger-Alberti W et al. Cosmet Med 2015;1(15): Dermatological assessments Corresponding to the increase of skin hydration, the skin dryness was markedly reduced during the 4week treatment period (Figure 3). Skin redness, desquamation, oedema and cracking were very mild from the start of the application. No papules, blisters or skin erosions were present in any patient during the study. 13 Figure 3: Course of the parameter dryness evaluated by a dermatologist in relation to the use of different foam creams over a study period of 4 weeks 13 Adapted from Wigger-Alberti W et al. Cosmet Med 2015;1(15):

12 Subjective assessments The subjective assessments found that: 13 Itching was reduced by around one point, so that 90% of all patients reported no itched after 2 weeks of treatment Stinging and burning sensation was negligibly weak in all treatment groups Skin condition that was assessed as dry at the beginning of the study period got continuously better during the study (Figure 4) A marked improvement in tightness was seen by day 8 and remained at this improved level during the rest of the study Figure 4: Subjectively-assessed skin dryness in relation to the use of different foam creams over 4 weeks 13 Adapted from Wigger-Alberti W et al. Cosmet Med 2015;1(15): The analysis of the subjective questionnaire found that after application of the foam creams: 13 Over 80% of patients described the improvement of their skin condition as good or very good Over 80% assessed the tolerability of the product used as very good 95% of those using GlucoRx Allpresan diabetic Intensive and 90% of the users of the other two groups perceived the application to be very good or good 80% of the users described absorption of the foam cream in comparison with other creams and lotions as very good or good Over 95% of users perceived the risk of slipping as moderate to negligible 75% to 90% of users declared they could put their socks on after the application of the foam cream quickly or very quickly 80% of users preferred the foam cream over other creams and lotions More than 85% of users reported that the option of a foam cream increased their willingness to conduct daily foot care All participants would recommend the foam cream they used to other diabetic patients 12

13 Safety No adverse effects of the foam creams occurred during the study. 13 Summary All three foot foam cream formulations used over the foot and between the toes showed a moisturising effect while no increase of bacterial colonisation was observed. These effects can be attributed to the particular texture of the foam cream used and not to the inclusion of the antibacterial components microsilver or polyhexanide. Both dermatological and subjective assessments showed an improvement in symptoms over the 4-week treatment period, with many symptoms improving after 1 week of use. All three products were well accepted by the patients, with 80% preferring a foam cream to a conventional lotion or cream and 85% of them more willing to carry out daily foot care with a foam cream. The majority of patients (>80%) assessed the improvement in their skin condition as very good or good and 85% preferred how the foam cream was applied and absorbed to that of a conventional lotion or cream. A reduced risk of slipping after application of the foam cream was assessed. 13 Study by Proksch An efficacy test and application test was carried out on GlucoRx Allpresan diabetic foam cream Intensive in 20 patients with diabetes. The foam cream was applied twice a day for 28 days to two areas: inside of the forearm and the foot/ankle, with an untreated area on the inside of the forearm acting as a control. The foam cream was found to significantly increase skin hydration on both test areas in comparison with the control area (p<0.05). Skin hydration on the forearm following GlucoRx Allpresan foam cream use increased by 32.2% after 14 days and by 38.7% after 28 days, and by 47.6% and 49.5% respectively on the foot/ankle. Skin smoothness on the forearm was also significantly increased on the test areas in comparison with the control area (p<0.05): by 9.7% after 14 days and by 17.5% after 28 days. After both 14 and 28 days of treatment, a significant (p<0.05) improvement in satisfaction with the skin condition and in experienced pruritus was seen with respect to the evaluated treatment area. 22 Study by Bristow GlucoRx Allpresan diabetic foam cream INTENSIVE (10% urea) was found to be as effective as a non-foaming 10% urea cream in patient and podiatrist evaluation study (n=20 patients with dry feet/heels). GlucoRx Allpresan foam cream was applied to one foot (test foot) and a non-foaming 10% urea cream was applied to the other foot (control foot), both applied twice daily for 14 days. At baseline there was no significant difference in the clinically measured dry skin score between the test and control foot overall. 23 When the feet were assessed at day 14, there was a significant reduction in overall dryness scores for both feet in all patients. Mean dryness scores in the test foot reduced from 5.90 at baseline to 2.00 at day 14 (p<0.000). In the control foot mean dryness scores reduced from 5.90 at baseline to 2.10 at day 14 (p<0.000). Efficacy of the test product was rated by clinicians as good (35%) to excellent (45%) and tolerability as good (15%) to excellent (85%) in all participants. 23 Patient evaluations showed overall a high level of satisfaction with the product, showing overall agreement with the benefits of the test product. Participating podiatrists felt that a foam cream promoted less wastage. They also felt that owing to the texture and application of the foam, GlucoRx Allpresan foam cream could make an excellent post-operative application to be kept in the surgery for patients following podiatry treatment, as it is clean and quick to apply and didn t need to be worked in as much as creams, saving practitioners time at the end of a consultation. 23 Budget impact Foot problems in people with diabetes have a significant financial impact on the NHS through primary care, community care, outpatient costs, increased bed occupancy and prolonged stays in hospital. It is estimated that around 650 million (or 1 in every 150 that the NHS spends) is spent on foot ulcers or amputations each year. 5 People using GlucoRx Allpresan diabetic foam cream INTENSIVE (10% urea) required only 0.11g of product to cover the same area covered by 0.24g of a non-foaming 10% urea emulsion

14 Less than half the amount of GlucoRx Allpresan diabetic foam cream INTENSIVE is needed per application compared with a non-foaming 10% urea emulsion. 16,24 In another study in 20 subjects, on average, 35mL of GlucoRx Allpresan diabetic foam cream INTENSIVE was required for two weeks worth of treatment. 23 GlucoRx Allpresan diabetic foam cream is the only urea-containing preparation specifically indicated for use in people with diabetes. 33 Table 3: Basic NHS list price 33,34 Product Indication Pack size GlucoRx Allpresan diabetic foam cream BASIC Dry, sensitive foot skin in diabetic patients 125mL: mL: 9.75 GlucoRx Allpresan diabetic foam cream INTENSIVE Very dry to chapped foot skin in diabetic patients 125mL: mL:

15 Appendix 1: Prescribing Information GlucoRx Allpresan diabetic Foam Cream BASIC Intended purpose GlucoRx Allpresan diabetic Foam Cream BASIC is a medical device for the specific treatment of dry and sensitive foot skin in patients with diabetes mellitus. Its special properties also make it suitable for the treatment of wound edges. GlucoRx Allpresan diabetic Foam Cream BASIC boosts the skin s barrier function, thus protecting against skin infections and ulcerations. Properties The specially designed active formula forms a breathable, two-dimensional protective coating. It strengthens the barrier function, protects against external impacts, and reduces mechanical stresses such as friction without impairing natural skin function. The skin is optimally supplied with moisture, and Pentavitin also guards against moisture loss. Reduces roughness, counteracts pressure marks and smooths the skin. Use Mornings and evenings, apply an amount about the size of a hazelnut or walnut to the affected areas of Side effects The use of GlucoRx Allpresan diabetic may cause temporary skin irritation (e.g. burning, itching, reddening), especially if the foam cream containing urea is applied to very irritated areas of skin. Contraindications Do not use if there is known sensitivity to any of the ingredients. Do not use on infants or children under the age of 5 years. Interactions Urea can increase the release of other active ingredients from other external-use products, and promote their penetration into the skin. Please ask your doctor or pharmacist if you are using other external-use products. Ingredients Aqua, Butane, Urea, Decyl Oleate, Octyldodecanol, Cetearyl Alcohol, Propane, Stearic Acid, Propylene Glycol, Glycerin, Glyceryl Stearate, Panthenol, Saccharide Isomerate (Pentavitin ), Undecyl Alcohol, Allantoin, Potassium Lauroyl Wheat Amino Acids, Palm the feet. Also beneficial for use between the toes. GlucoRx Allpresan diabetic Foam Cream offers excellent convenience in use, since it is very easy to rub in. It can be applied very quickly without leaving behind an unpleasant greasy film. There is reduced risk of slipping, and you can put on your stockings even compression stockings immediately after use. Shake well before each use, and hold the container upright when applying (please ensure the can is in the upright position and do not tilt during use!) Never apply to the eye region or mucus membranes, or in open wounds. Do not use GlucoRx Allpresan diabetic Foam Cream BASIC once the expiration date has passed. For external use only. Glycerides, Capryloyl Glycine, Sodium Lauroyl Sarcosinate, Sodium Citrate, Citric Acid. Pentavitin made by Pentapharm Ltd. Points to consider Warning. Pressurised container: May burst if heated. Keep away from heat, hot surfaces, sparks, open flames and other ignition sources. No smoking. Do not spray on an open flame or other ignition source. 9 % by mass of the contents are flammable. Do not pierce or burn, even after use. Protect from sunlight. Do not expose to temperatures exceeding 50 C/122 F. Keep out of reach of children. Use only in well-ventilated areas. 15

16 GlucoRx Allpresan diabetic Foam Cream INTENSIVE Intended purpose GlucoRx Allpresan diabetic Foam Cream INTENSIVE is a medical device for the specific treatment of very dry to chapped foot skin in patients with diabetes mellitus. Its special properties also make it suitable for the treatment of wound edges. GlucoRx Allpresan diabetic Foam Cream INTENSIVE promotes the healing process and supports recovery of the damaged skin barrier. Properties The specially designed active formula forms a breathable, two-dimensional protective coating. It strengthens the barrier function, protects against external impacts, and reduces mechanical stresses such as friction without impairing natural skin function. The skin is optimally supplied with moisture, and Pentavitin also guards against moisture loss. Relieves itching, counteracts pressure marks, and also helps to prevent calluses. Use Mornings and evenings, apply an amount about the size of a hazelnut or walnut to the affected areas of the feet. Also beneficial for use between the toes. GlucoRx Allpresan diabetic Foam Cream offers excellent convenience in use, since it is very easy to Side effects The use of GlucoRx Allpresan diabetic may cause temporary skin irritation (e.g. burning, itching, reddening), especially if the foam cream containing urea is applied to very irritated areas of skin. Contraindications Do not use if there is known sensitivity to any of the ingredients. Do not use on infants or children under the age of 5 years. Interactions Urea can increase the release of other active ingredients from other external-use products, and promote their penetration into the skin. Please ask your doctor or pharmacist if you are using other external-use products. Ingredients Aqua, Urea, Butane, Decyl Oleate, Octyldodecanol,Cetearyl Alcohol, Propane, Stearic Acid, Propylene Glycol, Glycerin, Glyceryl Stearate, Panthenol, Saccharide Isomerate (Pentavitin ), Undecyl Alcohol, Allantoin, Potassium Lauroyl Wheat Amino Acids, Palm Glycerides, Capryloyl Glycine, Sodium Lauroyl Sarcosinate, Sodium Citrate, Citric Acid. rub in. It can be applied very quickly without leaving behind an unpleasant greasy film. There is reduced risk of slipping, and you can put on your stockings even compression stockings immediately after use. Shake well before each use, and hold the container upright when applying (please ensure the can is in the upright position and do not tilt during use!) Never apply to the eye region or mucus membranes, or in open wounds. Do not use GlucoRx Allpresan diabetic Foam Cream INTENSIVE once the expiration date has passed. For external use only. Pentavitin made by Pentapharm Ltd. Points to consider Warning. Pressurised container: May burst if heated. Keep away from heat, hot surfaces, sparks, open flames and other ignition sources. No smoking. Do not spray on an open flame or other ignition source. 9 % by mass of the contents are flammable. Do not pierce or burn, even after use. Protect from sunlight. Do not expose to temperatures exceeding 50 C/122 F. Keep out of reach of children. Use only in well-ventilated areas. 16

17 References 1. Haak T. Dry skin and diabetic foot syndrome. Foamcreams in daily routine care. Thieme Prax Rep. 2013;11(5): Vuorisalo S et al. Treatment of diabetic foot ulcers. J Cardiovasc Surg. 2009;50(3): Diabetes UK. Diabetes. Facts and stats. Version 5. Revised December Available from: Date accessed February Fohles E. Foam creams provide additional benefits as skin care products in diabetes mellitus. DermoTopics. 2011;August. 5. NICE. Diabetic foot problems: prevention and management. NICE Guideline. 2015; Available from: Date accessed February SIGN. Management of diabetes. Guideline Available from: Date accessed February Apelqvist J et al. Practical guidelines on the management and prevention of the diabetic foot. Based upon the International Consensus on the Diabetic Foot (2007). Prepared by the International Working Group on the Diabetic Foot. Diabetes Metab Res Rev. 2008;24(Suppl 1):S181 S Proksch E. Skin disorders in diabetes mellitus. Thieme Prax Rep. 2013;11(5): Edmonds M. Diabetic foot ulcers. Practical treatment recommendations. Drugs. 2006;66(7): Tidy C. Diabetes, Foot Care and Foot Ulcers. 2014; Available from: Date accessed February Baker N et al. Effects of a urea-based moisturiser on foot xerosis in people with diabetes. Diabet Foot J. 2008;11(4): Daniels R. Foam-creams. Effective skin care in patients with diabetes mellitus. Thieme Prax Rep. 2013;11(5): Wigger-Alberti W et al. Foot care in diabetes: Adequate care of dry and sensitive skin for diabetic foot. Cosmet Med. 2015;1(15): Neubourg Pharma (UK) Ltd. GlucoRx Allpresan diabetic Foam Cream Basic. Available from: Allpresan.uk.com/product/diabeticfoamcream-basic/. Date accessed February Neubourg Pharma (UK) Ltd. Data on file. [001] 16. Neubourg Pharma (UK) Ltd. GlucoRx Allpresan diabetic Foam Cream Intensive. Available from: Allpresan.uk.com/product/diabetic-foamcream-intensive/. Date accessed February Pentapharm. Pentavitin. Available from: /pdf/pentavitin_product_description.pdf. Date accessed February Ebner F et al. Topical use of dexpenthenol in skin disorders. Am J Clin Dermatol. 2002;3(6): BMJ Group and Pharmaceutical Press. BNF Emollients. Available from: ent/index.htm. Date accessed February Proksch E. Wirksamkeitsprüfung und Anwendungstest mit Allpremed diabetic 10% Urea Fuß plus. Universitätsklinikum Schleswig- Holstein European Parliament and Council of the European Union. Directive 2007/47/EC of the European Parliament and of the Council. Off J Eur Union [Internet]. 2007;(September):L 247/21 L 247/55. Available from: es/revision_docs/ en_en.pdf. Date accessed February Proksch E. Efficacy test & user trial conducted with Allpremed diabetic 10 % Urea Fuß plus Bristow I. Evaluation report: A practitioner & patient evaluation of GlucoRx Allpresan diabetic intensive foam cream versus equivalent emollient in the treatment of dry skin on the foot Neubourg Skin Care GmbH & Co. Expert report. Definition of the quantity applied of both products. GlucoRx Allpresan(R) Foam Cream. DT No.:68/07/ Hex N et al. Estimating the current and future costs of Type 1 and Type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs. Diabet Med. 2012;29(7): Morgan N. What you need to know about xerosis in patients with diabetic feet. Wound Care Advis. 2013;2(4): International Working Group on the Diabetic Foot. IWGDF Guidance on the prevention of foot ulcers in at-risk patients with diabetes. Available from: Date accessed February Kerr M. Foot care for people with diabetes: the economic case for change. NHS Diabetes 2012;March. Available from: re/footcare-for-people-withdiabetes.pdf. Date accessed February Bader M. Diabetic foot infection. Am Fam Physician. 2008;78(1): NHS England. 2015/16 General Medical Services (GMS) contract Quality and Outcome Framework (QOF). Available from: Date accessed February Kishore P. Diabetes Mellitus. Merck Manual. Available from: Date accessed February Pan M et al. Urea: A comprehensive review of the clinical literature. Dermatol Online J. 2013;19(11):doj: Haymarket Medical Media. MIMS. 2015; Available from: Date accessed February NHS Business Services Authority - NHS Prescription Services. Drug Tariff. Available from: aspx. Date accessed February