Efficacy and Safety of Novel Formulation of Clobetasol Propionate 0.025% Cream in Indian Moderate-to-Severe Psoriasis Patients: Phase-2a, Randomized 3-Arm Study.

INTRODUCTION: Clobetasol propionate (0.05% standard dose formulation), a topical corticosteroid, leads to systemic side-effects like hypothalamic-pituitary-adrenal (HPA) axis suppression at doses as low as 2 g/day. The aim of this study was to evaluate HPA axis suppression, efficacy, and safety of clobetasol propionate (0.025%, formulation 5 and 13) versus currently marketed 0.05% cream in Indian patients with moderate-to-severe psoriasis. METHODS: In this phase 2a investigator-blinded study, patients aged ≥ 18 years with moderate-to-severe psoriasis were randomized 1:1:1 to receive clobetasol propionate 0.025% formulation 5, or 13, or 0.05% cream; twice daily for 28 days. Safety endpoints included adrenocorticotropic hormone (ACTH) test results at day 28 (primary), and local tolerability at each visit (burning/stinging/pruritus, secondary). Efficacy endpoints included Psoriasis Global Assessment (PGA) score. RESULTS: Overall, 88 patients received clobetasol propionate 0.025% formulation 5 and 13 (n = 29 for both) and 0.05% cream (n = 30). At day 28, the proportion of patients with an abnormal ACTH stimulation test (cortisol levels ≤ 18 µg/dl) was numerically lower in 0.025% formulations: 5 (20.7%) and 13 (17.2%) compared with 0.05% cream (30.0%), (p = 0.320). Decrease in burning/stinging /pruritus scores were comparable in all treatment groups and PGA success rates were higher with 0.025% formulations: 5 (38.9%) and 13 (36.8%) compared with 0.05% cream (30.8%). CONCLUSION: Clobetasol propionate 0.025% could be an effective treatment for moderate-to-severe psoriasis compared with 0.05% cream, demonstrating comparable efficacy with a better systemic safety profile. TRIAL REGISTRATION NUMBER: REF/2018/01/016779.

Minocycline Extended-Release Comparison with Doxycycline for the Treatment of Rosacea: A Randomized, Head-to-Head, Clinical Trial.

OBJECTIVE: Minocycline efficacy for the treatment of papulopustular rosacea (PPR) has not been evaluated in clinical trials at levels demonstrated to stay below the antimicrobial threshold. We assessed the efficacy, safety, and dose response of DFD-29, a minocycline extended-release oral capsule. Two studies are reported (NCT03340961). METHODS: A single-center open-label, three-arm, Phase I pharmacokinetic study randomized 24 healthy subjects aged 18 to 45 years to receive 21 days of once-daily dosing with DFD-29 40 or 20mg, or doxycycline 40mg. Blood samples were collected over 24 hours on Days 1 and 21 to plot mean plasma concentration levels. A multicenter Phase II clinical trial randomized 205 subjects with mild-to-severe PPR 1:1:1:1 to receive once-daily DFD-29 40 or 20mg, doxycycline 40mg, or placebo for 16 weeks. Co-primary endpoints were the proportion of subjects achieving treatment success (IGA grade 0 or 1 and ≥2-grade improvement) at Week 16, and a reduction in total inflammatory lesion count at Week 16. RESULTS: Pharmacokinetic analysis demonstrated that minocycline plasma levels of DFD-29 40mg were approximately half those of doxycycline 40mg after 21 days, with DFD-29 20mg even lower, demonstrating a dose response. In the Phase II trial, DFD-29 40mg met both co-primary endpoints, achieving IGA treatment success in 66.0 percent subjects versus 11.5 percent placebo (p<0.0001), 31.9 percent DFD-29 20mg (p=0.007), and 33.3 percent doxycycline 40mg (p<0.0010), and a mean reduction in lesion counts of -19.2 versus -7.3 placebo (p<0.0001), -12.6 DFD-29 20mg (p=0.0070), and -10.5 doxycycline 40mg (p=0.0004). LIMITATIONS: MIC values and plasma concentrations shown for antibacterial threshold data are mean values; fast absorbers/slow metabolizers could exceed the threshold, causing resistance selection pressure. CONCLUSION: DFD-29 40mg demonstrated significantly greater efficacy than placebo, DFD-29 20mg, and doxycycline 40mg at plasma concentrations predicted to be below the antimicrobial threshold for the treatment of PPR.

Betamethasone dipropionate spray 0.05% alleviates troublesome symptoms of plaque psoriasis.

Patients consider pruritus and scaling to be the most bothersome symptoms of psoriasis. Psoriatic plaques on the knees and elbows are widely considered difficult to treat because of the thicker stratum corneum, which reduces skin hydration and topical absorption. Betamethasone dipropionate (BD) spray 0.05% is a topical steroid with demonstrated efficacy in treating plaque psoriasis. Post hoc analyses of 2 phase 3 trials were done to assess the efficacy of BD spray in relieving the symptom of itching and improving the signs of erythema, scaling, and plaque elevation on plaques located on the knees and elbows vs its vehicle and an augmented BD (AugBD) lotion 0.05%. Betamethasone dipropionate spray reduced the incidence of pruritus, with approximately half of patients who reported itching at baseline showing complete itch relief by day 4. Betamethasone dipropionate spray also reduced the signs of psoriasis on knee and elbow plaques in more patients than AugBD lotion at day 4, though the differences were not statistically significant. Efficacy was similar between the 2 formulations on days 8 and 15. Betamethasone dipropionate spray rapidly relieved2 of the most bothersome symptoms of psoriasis and improved psoriatic signs in hard-to-treat knee and elbow plaques.

Bioavailability, Pharmacokinetics, and Transepidermal Water Loss of Short Contact Tazarotene Lotion 0.1% Versus Tazarotene (Tazorac®) Cream 0.1.

Objective: Two clinical studies were conducted to 1) assess the pharmacokinetic (PK) properties of tazarotene and tazarotenic acid in DFD-03 lotion (a 1-minute, short-contact formulation for the topical treatment of acne vulgaris) and tazarotene cream 0.1% and 2) to evaluate transepidermal water loss (TEWL) with DFD-03 lotion, tazarotene gel (0.1%), or vehicle. Design: The PK study included a single-center, randomized, multiple-dose, laboratory-blinded, open-label, parallel-design, and the TEWL study included a multiple-dose, within-subject comparison design. Participants: The PK study included healthy adult men aged 18 to 40 years (n=43), and the TEWL study included healthy adults, male or female, aged 18 to 40 years (n=24). Measurements: PK was assessed via Cmax, AUC0-12, AUC0-24, Tmax, Cmin, Tmin, and fluctuation. TEWL was assessed via evaporimetry. Results: Tazarotene levels were very low due to rapid esterase hydrolysis to the primary active metabolite, tazarotenic acid. Tazarotenic acid AUC0-24 ratios (%) were at least two times higher when the test product was applied twice daily (Treatment-1) versus once daily (Treatment-2) on Days 7 and 14 (268.73% and 254.42%, respectively). Tazarotenic acid AUC0-24 ratios (%) were nearly 100 percent for Treatment-1 versus once-daily tazarotene cream 0.1% (Treatment-3) (99.36% and 83.21%, on Days 7 and 14, respectively). Starting on Day 7, DFD-03 lotion TEWL readings were significantly greater than vehicle (p≤0.05), except for on one study day. DFD-03 lotion TEWL readings were numerically greater (nonsignificant) than tazarotene gel. Conclusion: DFD-03 lotion was well-tolerated, increased TEWL when applied twice daily for one minute, and had a PK profile with similar overall exposure as compared with commercially available tazarotene formulations applied once daily for 12 hours.

Effect of a New Head Lice Treatment, Abametapir Lotion, 0.74%, on Louse Eggs: A Randomized, Double-Blind Study.

Few head lice treatments have demonstrated effectiveness against louse eggs. Abametapir, a metalloproteinase inhibitor, is able to target metalloproteinases critical to egg hatching and louse development. In this double-blind, phase 2 study, 50 subjects aged ≥3 years with active head lice infestation were randomized to receive a single treatment of abametapir lotion, 0.74%, or vehicle (control), applied to scalp and hair for 10 minutes. Ovicidal efficacy was measured by recording the hatch rate of eggs collected from each subject's hair before and after treatment and incubated for 14 days. With abametapir, 100% of treated eggs remained unhatched compared with 64.0% for vehicle. Accounting for pretreatment hatch rates, the absolute reduction in egg hatching was 92.9% for abametapir versus 42.3% for vehicle (P < .0001). The most frequently reported adverse event was rash (16%). Abametapir lotion, 0.74%, demonstrated significant ovicidal activity against head lice eggs with a single application.

Clinical studies evaluating abametapir lotion, 0.74%, for the treatment of head louse infestation.

BACKGROUND: There is a need for better control of head louse infestations. Abametapir is an inhibitor of metalloproteinases critical for louse survival and egg development. The efficacy of abametapir lotion, 0.74%, was assessed for its ability to clear head louse infestations after a single application. METHODS: Two randomized, double-blind, multicenter, vehicle-controlled studies were conducted in subjects aged 6 months and older to compare the effectiveness of abametapir lotion versus vehicle control for eliminating head louse infestations without nit combing. Abametapir lotion was applied to dry hair for 10 minutes on day 0 and then rinsed with water. The primary endpoint was the proportion of index subjects (youngest household member with ≥ 3 live lice at screening) in the intent-to-treat population who were louse free at all follow-up visits through day 14. Older household members with one or more live lice at screening were designated as nonindex subjects and treated as per the index subject within their household. RESULTS: In the intent-to-treat population (index subjects, N = 216), 81.5% of subjects treated with abametapir lotion were louse free through day 14 after a single treatment, versus 49.1% with vehicle (P < 0.001). For the combined index and nonindex population (N = 704), 85.9% were louse free through day 14 in the abametapir group, versus 61.3% in the vehicle group (P < 0.001). The most frequently reported adverse events were erythema (4.0%), rash (3.2%), and skin burning sensation (2.6%). CONCLUSION: Abametapir lotion, 0.74%, was effective at clearing active head louse infestations through day 14 in subjects aged 6 months and older. All adverse events (including one serious but unrelated to study drug) resolved uneventfully.

Efficacy, Safety, and Potency of Betamethasone Dipropionate Spray 0.05%: A Treatment for Adults with Mild-to-moderate Plaque Psoriasis.

Objective: A spray formulation of betamethasone dipropionate 0.05% (BD spray 0.05%; Sernivo™ [betamethasone dipropionate] Spray 0.05%; Promius Pharma, LLC; Princeton, New Jersey, USA) has been developed for the topical treatment of psoriasis. The objective of these studies was to evaluate the efficacy, safety, and potency of BD spray 0.05%. Design, Setting, Participants, and Measurements: Efficacy and safety were assessed in a randomized, vehicle-controlled, double-blind study in adults with moderate plaque psoriasis (ClinicalTrials.gov identifier: NCT01947491). Additionally, the potential for adrenal suppression and systemic absorption was evaluated in a randomized, open-label study in healthy adults (ClinicalTrials.gov identifier: NCT02070965). Potency was measured in two single-point, randomized, evaluator-blinded studies in healthy adults. Results: BD spray 0.05% was significantly more effective than the vehicle spray in subjects with moderate plaque psoriasis after three, 14, and 28 days of twice-daily treatment. The efficacy of BD spray 0.05% was similar to augmented BD lotion 0.05% after 14 days of treatment. The safety of BD spray 0.05% was similar to that of the vehicle spray over 28 days and to that of augmented BD lotion 0.05% over 14 days. Under maximal use conditions for up to 29 days, the potential for adrenal suppression was no greater with BD spray 0.05% than with a 15-day regimen of augmented BD lotion 0.05%. There was less systemic absorption of BD from BD spray 0.05% than from augmented BD lotion 0.05%. Studies classify BD spray 0.05% as a midpotent corticosteroid. Conclusions: BD spray 0.05%, a midpotent corticosteroid, is an effective and well-tolerated treatment for adults with mild to moderate plaque psoriasis.

Treatment Satisfaction, Product Perception, and Quality of Life in Plaque Psoriasis Patients Using Betamethasone Dipropionate Spray 0.05.

Objective: To assess patient-reported satisfaction, efficacy, and tolerability associated with the use of betamethasone dipropionate spray 0.05% when applied twice daily in subjects with moderate plaque psoriasis. Design: This was an open-label, multicenter study involving 45 patients with moderate plaque psoriasis, with the aim of evaluating patient-reported outcomes with betamethasone dipropionate spray 0.05%. Patients treated all affected areas twice daily with betamethasone dipropionate (BD) spray 0.05% for 28 days per label instructions. Measurements: Outcome measures included the Treatment Satisfaction Questionnaire for Medication (TSQM), Dermatology Life Quality Index (DLQI), Investigators Global Assessment (IGA), and Total Sign Score (TSS). In addition, the lesions were photographed at baseline (Day 1) and on Day 8, Day 14, and Day 29. Results: The results indicated that BD spray 0.05% treatment is associated with improved quality of life. BD spray 0.05% also led to improved IGA and TSS values and a reduction in the percentage of body surface area affected. Conclusion: In subjects with moderate plaque psoriasis, BD spray 0.05% demonstrated good levels of patient satisfaction and quality of life measures, in combination with improvements in the global assessment of disease and the level of itching experienced by subjects.

Non-alcoholic fatty liver disease: need for a balanced nutritional source.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are an increasingly common chronic liver disease closely associated with diabetes and obesity that have reached epidemic proportions. Reports on the prevalence of NAFLD have suggested that 27-34% of the general population in the USA and 40-90% of the obese population worldwide have this disease. Increasing urbanisation rate and associated inappropriate lifestyle changes are not only the risk factors of diabetes, but also unmask genetic predisposition in various populations for the metabolic syndrome and its manifestations including NAFLD and NASH. Lifestyle modifications and balanced nutrition are among the foremost management strategies along with ursodeoxycholic acid, metformin, vitamin E and pentoxifylline. Although weight reduction associated with current therapeutic strategies has shown some promise, maintaining it in the long run is largely unsuccessful. With the safety of pharmacotherapy still being uncertain and can be started only after confirmation, other reasonable interventions such as nutrition hold promise in preventing disease progression. The role of dietary components including branched-chain amino acids, methionine, choline and folic acid is currently being evaluated in various clinical trials. Nutritional approaches sought to overcome the limitations of pharmacotherapy also include evaluating the effects of natural ingredients, such as silymarin and spirulina, on liver disease. Understanding the specific interaction between nutrients and dietary needs in NAFLD and maintaining this balance through either a diet or a nutritional product thus becomes extremely important in providing a more realistic and feasible alternative to treat NAFLD. A planned complete nutritional combination addressing specific needs and helping to prevent the progression of NAFLD is the need of the hour to avert people from ending up with complications.