Fixed-Combination Halobetasol Propionate and Tazarotene in the Treatment of Psoriasis: Narrative Review of Mechanisms of Action and Therapeutic Benefits

Psoriasis is a lifelong disease associated with cycles of remission and relapse. Topical treatments are the front line of psoriasis therapy for most patients and have antiproliferative, anti-inflammatory, and immunosuppressive mechanisms of action. Novel fixed-dose combinations of topical therapeutic agents are becoming increasingly available, leveraging multiple mechanisms of action to improve safety and efficacy with formulations that are easier to use and may allow for the use of lower doses of active ingredients. A fixed-combination lotion containing the potent-to-super-potent corticosteroid halobetasol propionate (HP) and the retinoid tazarotene (HP 0.01%/TAZ 0.045%) was recently developed using polymeric emulsion technology. This new formulation technology allows for more uniform and efficient delivery of the active ingredients at lower doses than conventional monotherapy formulations of either ingredient while providing enhanced hydration and moisturization. This review provides an up-to-date overview of the therapeutic mechanisms of action of HP and TAZ, the rationale behind the development of HP 0.01%/TAZ 0.045% lotion, and clinical trials data on the efficacy, safety and tolerability, and maintenance of therapeutic effect with HP 0.01%/TAZ 0.045% lotion in the treatment of moderate-to-severe plaque psoriasis

Improvements in Acne and Skin Oiliness with Tazarotene 0.045% Lotion in Patients with Oily Skin

BACKGROUND: Excessive sebum production is a factor in acne development. Tazarotene 0.045% lotion has demonstrated reductions in acne lesions and acne-induced sequalae. OBJECTIVE: Evaluate efficacy, changes in skin oiliness, and safety with tazarotene 0.045% lotion in participants with moderate-to-severe acne and oily skin. METHODS: In two phase 3, double-blind, 12-week studies (NCT03168321; NCT03168334), participants aged ≥9 years with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene 0.045% lotion or vehicle lotion (N = 1,614). This pooled, post hoc analysis included only participants self-categorized with oily skin at baseline on the Acne Quality of Life questionnaire item 19 (scores: 0 [extremely oily] to 6 [not at all oily]). Inflammatory/noninflammatory lesion counts, treatment success, skin oiliness, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability were evaluated. RESULTS: In all participants with oily skin (n = 793), tazarotene provided greater reductions in inflammatory/noninflammatory lesions (P \u3c 0.001, both) and greater treatment success rates versus vehicle (P \u3c 0.01) at week 12. Over two-thirds of polymeric lotion-treated participants had subjective skin oiliness reductions by week 12, with around a third reporting \u27low/not\u27 oily skin. Tazarotene TEAE rates were similar to the overall population. CONCLUSION: Once-daily treatment with tazarotene 0.045% polymeric emulsion lotion may help improve patient-perceived skin oiliness in those with moderate-to-severe acne

32970 Efficacy and safety of a fixed-dose clindamycin 1.2%, benzoyl peroxide 3.1%, and adapalene 0.15% gel for moderate-to-severe acne: Randomized phase 2 and phase 3 studies of the first triple-combination drug

A 3-pronged approach to acne treatment—combining an antibiotic, antibacterial, and retinoid—may provide greater efficacy and tolerability than single/double treatments while potentially reducing antibiotic resistance and increasing patient compliance. Clindamycin 1.2%/BPO 3.1%/adapalene 0.15% (IDP-126) gel is the first triple-combination, fixed-dose topical acne product in development that addresses the major pathophysiological abnormalities in acne patients. A phase 2 (N = 741) and two phase 3 (N = 183; N = 180), double-blind, randomized, 12-week studies enrolled participants aged ≥9 years with moderate-to-severe acne. Participants were randomized to receive once-daily IDP-126 or vehicle; the phase 2 study included 3 additional randomization arms containing dyad gels: BPO/adapalene; clindamycin phosphate/BPO; and clindamycin phosphate/adapalene (data not shown). Endpoints included participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in inflammatory and noninflammatory lesion counts. Treatment-emergent adverse events (TEAEs) were also assessed. In all 3 studies at week 12, half of participants achieved treatment success with IDP-126 (phase 2: 52.5%; phase 3: 49.6%, 50.5%) versus less than one-fourth with vehicle (8.1%; 24.9%, 20.5%; P \u3c.01, all). IDP-126 resulted in \u3e70% reductions in inflammatory and noninflammatory lesions at week 12, significantly greater than vehicle (range: inflammatory, 75.7%-80.1% vs 50.4%-59.6%; noninflammatory, 71.0%-73.3% vs 45.8%-49.0%; P \u3c.001, all). Most TEAEs were of mild-moderate severity, and \u3c4% of IDP-126-treated participants discontinued study/treatment due to AEs. The innovative fixed-dose, triple-combination IDP-126 gel was efficacious and well tolerated in three clinical studies of children, adolescents, and adults with moderate-to-severe acne

Optimized formulation for topical application of a fixed combination halobetasol/tazarotene lotion using polymeric emulsion technology

Background: Successful clinical data on halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in moderate-to-severe plaque psoriasis are published. This article charts its formulation development. Methods: Dermal deposition, clinical efficacy and synergistic effect of HP and TAZ delivered by polymeric emulsion technology was compared to HP 0.05% cream (Ultravate) and TAZ 0.1% cream (Tazorac); skin hydration and barrier maintenance with vehicle lotion through Trans Epidermal Water Loss (TEWL) and corneometry using human cadaver tissue; and steroid potency by vasoconstrictor assay (VCA) in healthy volunteers. Safety and tolerability evaluated in clinical studies and patient preference questionnaire. Results: HP/TAZ lotion, using polymeric emulsion technology demonstrated better active ingredient delivery than HP 0.05% or TAZ 0.1% creams; supported by synergistic clinical data, with high HP potency outcome. Efficacy was rapid and sustained posttreatment. Layering TAZ 0.1% cream onto HP 0.05% cream had a negative effect on receptor phase levels. HP/TAZ lotion provided rapid and sustained increases in skin moisturization and gradual decreases in TEWL. Most subjects responded favorably to questions on the physical attributes of the vehicle lotion. Conclusions: Fixed combination HP 0.01%/TAZ 0.045% lotion formulation utilizing innovative polymeric emulsion technology and optimal selection of solvents/emollients/humectants, has recently been developed. Features inherent in the technology translate into rapid, sustained efficacy, low irritation and good patient acceptance

Efficacy and safety of topical oxymetazoline cream 1.0% for the treatment of facial erythema associated with rosacea: Findings from the second of 2 pivotal trials

Introduction: A phase 3 pivotal trial examined the efficacy and safety of oxymetazoline, a specific α1A-adrenoceptor agonist, for treatment of moderate to severe persistent facial erythema associated with rosacea. Methods: In this multicenter double-blind trial, eligible patients were randomized 1:1 to receive vehicle or oxymetazoline hydrochloride cream 1.0% (oxymetazoline) applied topically to the face once daily for 29 days. The primary efficacy outcome was the proportion of patients with ≥2-grade decrease from baseline on Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) at 3, 6, 9, and 12 hours postdose on day 29. Safety assessments included treatment-emergent adverse events (TEAEs), inflammatory lesions, dermal tolerability, and posttreatment rebound erythema (defined as composite CEA/SSA increase of 1-grade severity from baseline). Results: A total of 445 eligible patients (mean age: 50.3 years; 78.7% females) were randomized (oxymetazoline, n = 224; vehicle, n = 221). Most patients had moderate erythema (CEA: 84.0%; SSA: 91.5%). On day 29, the proportions of patients achieving ≥2-grade composite improvement in both CEA/SSA at 3, 6, 9, and 12 hours postdose were significantly greater with oxymetazoline vs vehicle at each time point ( P ≤ .03) and overall ( P = .001). Improvements in individual CEA and SEA components were also significantly greater with oxymetazoline vs vehicle on day 29 (overall P = .011). Incidences of TEAEs were low (oxymetazoline: 25.1%; placebo: 21.3%); most were mild or moderate in severity. The most common TEAEs with oxymetazoline and vehicle, respectively, were rosacea (3.1% [related to papules and/or pustules in all 7 patients] and 0.5% [inflammatory flare of rosacea in 1 patient]), application-site pruritus (1.8%, 1.8%), application-site dermatitis (1.8%, 0.0%), and headache (1.8%, 4.1%). Discontinuations due to TEAEs were low (oxymetazoline: 2.7%; vehicle: 0.5%). No clinically meaningful between-group differences were observed for worsening of inflammatory lesions or dermal tolerability. Following treatment cessation, low proportions of patients experienced rebound erythema (oxymetazoline: 1.2%; vehicle: 0.0%). Conclusion: Topical oxymetazoline was safe and effective in the treatment of moderate to severe persistent facial erythema associated with rosacea. There was no apparent rebound effect following cessation of oxymetazoline treatment compared with that experienced following cessation of vehicle treatment

Dermal sensitization, safety, and tolerability of triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel from three clinical trials

Background Using a three-pronged acne treatment approach—combining an antibiotic, antimicrobial agent, and retinoid—may provide greater efficacy than monad or dyad treatments. Herein are the dermal sensitization, irritation, safety, and tolerability results from phase 1 and 2 studies of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) polymeric mesh gel. Methods Two phases 1, single-blind, vehicle-controlled dermal safety studies were conducted in healthy participants aged ≥18 years. One phase 2 (NCT03170388) double-blind, randomized, parallel-group, and vehicle-controlled study was conducted over 12 weeks in participants aged ≥9 years with moderate-to-severe acne. Results A total of 1,020 participants (IDP-126 gel, vehicle, or 1 of the 3 dyad gels [phase 2 only]) were included across the 3 studies (safety populations: n = 1,004). In the phase 1 studies, IDP-126 had no confirmed sensitization or contact dermatitis. IDP-126 (deemed “moderately irritating”) was significantly less irritating than commercially available BPO 2.5%/adapalene 0.3% gel. Conclusions The results from these three studies show that the triple-combination IDP-126 had a positive safety profile and was well tolerated in healthy participants and those with moderate-to-severe acn

Improvements in acne and skin oiliness with tazarotene 0.045% lotion in patients with oily skin

Background Excessive sebum production is a factor in acne development. Tazarotene 0.045% lotion has demonstrated reductions in acne lesions and acne-induced sequelae. Objective Evaluate efficacy, changes in skin oiliness, and safety with tazarotene 0.045% lotion in participants with moderate-to-severe acne and oily skin. Methods In two phase 3, double-blind, 12-week studies (NCT03168321; NCT03168334), participants aged ≥ 9 years with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene 0.045% lotion or vehicle lotion (N = 1614). This pooled, post hoc analysis included only participants self-categorized with oily skin at baseline on the Acne-Specific Quality of Life questionnaire item 19 (scores: 0 [extremely oily] to 6 [not at all oily]). Inflammatory/noninflammatory lesion counts, treatment success, skin oiliness, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability were evaluated. Results In all participants with oily skin (n = 793), tazarotene provided greater reductions in inflammatory/noninflammatory lesions (p < 0.001, both) and greater treatment success rates versus vehicle (p < 0.01) at week 12. Over two-thirds of polymeric lotion-treated participants had subjective skin oiliness reductions by week 12, with around a third reporting ‘low/not’ oily skin. Tazarotene TEAE rates were similar to the overall population. Conclusions Once-daily treatment with tazarotene 0.045% polymeric emulsion lotion may help improve patient-perceived skin oiliness in those with moderate-to-severe acne

Efficacy and safety of a fixed-dose clindamycin phosphate 1.2%, benzoyl peroxide 3.1%, and adapalene 0.15% gel for moderate-to-severe acne: Randomized Phase 2 and Phase 3 studies of the first triple combination drug

Background: A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-may provide greater efficacy and tolerability than single/double treatments while potentially reducing antibiotic resistance and increasing patient compliance. Clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% (IDP- 126) gel is the first triple-combination, fixed-dose topical acne product in development that addresses the major pathophysiological abnormalities in acne patients. The efficacy, safety, and tolerability of IDP-126 gel was evaluated in Phase 2 and 3 studies of patients with moderate-to-severe acne. Methods: A Phase 2 (N=741; NCT03170388) and two Phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, randomized, 12-week studies enrolled participants aged ≥9 years with moderate-to-severe acne. Participants were randomized to receive once-daily IDP-126 or vehicle; the Phase 2 study included three additional randomization arms containing dyad gels: BPO/adapalene; clindamycin phosphate/BPO; and clindamycin phosphate/adapalene (data not shown). Endpoints included participants achieving ≥2-grade reduction from baseline in Evaluator\u27s Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in inflammatory and noninflammatory lesion counts. Treatment-emergent adverse events (TEAEs) were also assessed. Results: In all three studies at Week 12, half of participants achieved treatment success with IDP-126 (Phase 2: 52.5%; Phase 3: 49.6%, 50.5%) versus less than one-fourth with vehicle (8.1%; 24.9%, 20.5%; P\u3c0.01, all). IDP-126 resulted in over 70% reductions in inflammatory and noninflammatory lesions at Week 12, significantly greater than vehicle (range: inflammatory, 75.7%-80.1% vs 50.4%-59.6%; noninflammatory, 71.0%-73.3% vs 45.8%-49.0%; P\u3c0.001, all). Most TEAEs were of mild-moderate severity, and less than 4 percent of IDP-126-treated participants discontinued study/treatment due to AEs. Conclusion: The innovative fixed-dose, triple-combination IDP-126 gel was efficacious and well tolerated in three clinical studies of children, adolescents, and adults with moderate-to-severe acne

Triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel for moderate-to-severe acne in children and adolescents: Randomized phase 2 study

BACKGROUND/OBJECTIVES: Topical clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel (IDP-126) is the first fixed-dose triple-combination formulation in development for acne. This post hoc analysis investigated efficacy and safety of IDP-126 in children and adolescents with moderate-to-severe acne. METHODS: In a randomized, double-blind phase 2 study (NCT03170388), participants ≥9 years of age with moderate-to-severe acne were eligible for randomization (1:1:1:1:1) to once-daily IDP-126, one of three dyad combination gels, or vehicle gel for 12 weeks. This post hoc analysis of pediatric participants (n = 394) included children and adolescents up to 17 years of age. Assessments included treatment success, inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. RESULTS: At Week 12, treatment success rates were significantly greater with IDP-126 (55.8%) than with vehicle (5.7%; p \u3c .001) or any of the dyad combinations (range: 30.8%-33.9%; p \u3c .01, all). Lesion reductions with IDP-126 were also significantly greater than with vehicle (inflammatory: 78.3% vs. 45.1%; noninflammatory: 70.0% vs. 37.6%; p \u3c .001, both) and 9.2%-16.6% greater than with any of the dyad combinations. Increases (improvements) from baseline in Acne-QoL domain scores were generally greater with IDP-126 than in any other treatment group. The most common treatment-related TEAEs across treatment groups were application site pain and dryness. Most treatment-related TEAEs were of mild-to-moderate severity. CONCLUSION: IDP-126 gel-a novel fixed-dose, triple-combination topical formulation for acne-demonstrated superior efficacy to vehicle and three dyad component gels and was well tolerated in children and adolescents with moderate-to-severe acne

Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug

BACKGROUND: A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. OBJECTIVES: We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. METHODS: In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator\u27s Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. RESULTS: A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P \u3c 0.05, all), corresponding to \u3e 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. CONCLUSIONS: Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017)