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 < .001) or any of the dyad combinations (range: 30.8%–33.9%; p < .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 < .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.     

A combination benzoyl peroxide and clindamycin topical gel compared with benzoyl peroxide, clindamycin phosphate, and vehicle in the treatment of acne vulgaris

A topical gel combining 5% benzoyl peroxide and 1% clindamycin as phosphate was evaluated in a 10-week randomized double-blind trial involving 287 patients with moderate to moderately severe acne. The combination agent demonstrated significantly greater reductions in inflammatory lesions than either of its active constituents (5% benzoyl peroxide and 1% clindamycin) or vehicle when used alone. Significantly greater reductions in comedos and improvements, as measured by both physicians' and patients' global evaluations, were obtained with the combination agent than with clindamycin or vehicle. The reduction in comedos and the global improvements were similar between the combination agent and benzoyl peroxide. The combination agent was well tolerated; the incidence of dry skin was similar to that found with benzoyl peroxide, and other adverse events were similar to that with vehicle. The improved efficacy obtained with combination therapy was accompanied by a safety profile similar to that of either constituent used alone.     

A comparative study of benzoyl peroxide and clindamycin phosphate for treating acne vulgaris

A water based 5% benzoyl peroxide gel (Benzac W5) was compared with topical 1% clindamycin phosphate solution (Cleocin T) in the treatment of acne vulgaris using a randomized, investigator blind study design. Lesion counts were significantly reduced in both treatment groups over the 12-week study period; however, the reduction of total lesions produced by benzoyl peroxide gel was significantly greater than that produced by clindamycin phosphate (P less than 0.05). Clindamycin phosphate had a milder effect on the skin surface in terms of peeling and drying than the benzoyl peroxide gel.     

Comparative evaluation of clindamycin phosphate 1% and clindamycin phosphate 1% with nicotinamide gel 4% in the treatment of acne vulgaris

Eighty patients with moderate acne vulgaris were enrolled from out-patient department for the comparative evaluation of clindamycin phosphate 1% and clindamycin phosphate 1% with nicotinamide gel 4%. In group I forty patients were given clindamycin phosphate 1% alone.ln group II forty patients were given clindamycin phosphate 1% and nicotinamide gel 4% in combination. The study did not show any added advantage of clindamycin phosphate 1% in combination with nicotinamide gel 4% over clindamycin phosphate 1% alone.     

Erythromycin 2% gel in comparison with clindamycin phosphate 1% solution in acne vulgaris

One hundred two patients with mild to moderate facial acne vulgaris completed a 12-week, investigator-masked, randomized, parallel-group comparison of a gel formation of erythromycin (2%) with clindamycin phosphate 1% solution. Patients were evaluated at a baseline visit and after 4, 8, and 12 weeks of twice-daily treatment. Both medications significantly reduced the numbers of papules and open and closed comedones. No significant differences in lesion count reductions were detected between the treatment groups after 8 and 12 weeks of treatment. By the end of 12 weeks, 48% of the patients in the erythromycin group and 47% in the clindamycin group had good or excellent responses to treatment. No patient was terminated from the study for side effects. Most patients, 65% in the erythromycin 2% gel group and 67% in the clindamycin phosphate 1% solution group, had a favorable impression of the overall cosmetic characteristics of their study medication.     

1 percent clindamycin phosphate solution versus 5 percent benzoyl peroxide gel in papulopustular acne

In a multicenter study, 60 patients suffering from mainly moderate papulopustular acne were treated to pically either with 1% clindamycin phosphate in alcoholic solution or with 5% benzoyl peroxide gel, 30 patients each. During the treatment period of 9 weeks, clinical controls with lesion counts were performed every 3 weeks and after a 3 weeks follow-up. The therapeutic efficacy according to the reduction of papules and pustules was 72% in the benzoyl peroxide group and 73% in the clindamycin group, the latter showing significantly less side effects. On account of its good therapeutic results, we consider topical treatment with clindamycin phosphate an important alternative to systemic antibiotic or topical benzoyl peroxide therapy in acne.     

Prospective, open-label, comparative study of clindamycin 1%/benzoyl peroxide 5% gel with adapalene 0.1% gel in Asian acne patients: efficacy and tolerability

Background  Used as individual agents, topical antibiotics and benzoyl peroxide are known to be effective in treatment of acne. Clindamycin phosphate 1% with benzoyl peroxide 5% (CDP/BPO) is a new combination gel, made by rationale, in that combination drug is more effective than either ingredients used alone. Adapalene 0.1% (ADA) is the third-generation retinoid, shown to be as effective as other topical retinoid with well tolerability.
Objectives  To compare the efficacy and tolerability in combination of CDP/BPO in comparison with ADA in Asian patients with mild to moderate acne vulgaris.
Methods  Total of 69 patients, including 31 patients for CDP/BPO group and 38 for ADA group, with mild to moderate acne vulgaris were enrolled for a 12-week prospective, randomized, open-label comparative study of topical agents. Efficacy was assessed by lesion counts, acne grading system, and global improvement. Adverse events were also evaluated in scale of 0 (none) to 3 (severe).
Results  Both CDP/BPO and ADA were effective in reducing lesion counts and acne severity scale and showed significant global improvement. However, CDP/BPO offered greater efficacy against inflammatory lesions than ADA. Both drugs were well tolerated with minimal adverse drug reactions.
Conclusion  Combination formulation of CDP/BPO and ADA were shown to be both effective in decreasing total, inflammatory, and non-inflammatory lesion counts along with well tolerability in Asian patients with mild to moderate acne vulgaris.

Conflicts of interest

None declared     

The comparative efficacy of benzoyl peroxide 5%/erythromycin 3% gel and erythromycin 4%/zinc 1.2% solution in the treatment of acne vulgaris

This randomized 10–week study compared the efficacy of benzoyl peroxide 5%/erythromycin 3% gel with erythromycin 4%/zinc 1.2% solution in 72 acne vulgaris patients. Physician global evaluations were significantly more improved (P 0.05) in the benzoyl peroxide 5%/erythromycin 3% gel treatment group compared to erythromycin 4%/zinc 1.2% solution at week 2 and at each subsequent biweekly clinical visit. Inflammatory lesions (papules/pustules) were significantly more reduced (P 0.005) in the benzoyl peroxide 5%/erythromycin 3% gel treatment group than the erythromycin 4%/zinc 1.2% solution at weeks 4 and 10. Comedones were significantly more reduced (P 0.001) in the benzoyl peroxide 5%/erythromycin 3% gel treatment group than in the erythromycin 4%/zinc 1.2% solution group at weeks 8 and 10. Patient efficacy evaluations significantly (P 0.001) favoured benzoyl peroxide 5%/erythromycin 3% gel to erythromycin 4%/zinc 1.2% solution.     

Clindamycin phosphate 1.2%- tretinoin 0.025% gel: vehicle characteristics, stability, and tolerability

An aqueous gel formulation containing solubilized clindamycin phosphate 1.2% and a stable combination of both solubilized and crystalline tretinoin 0.025% (clin/tret) has been evaluated in 3 pivotal phase 3 studies, among other studies including a 52-week trial. The pivotal studies enrolled 4550 participants 12 years and older with mild, moderate, and severe acne vulgaris. The combination clin/tret gel was effective in reducing both inflammatory and noninflammatory lesions and was well-tolerated. This article reviews important vehicle characteristics of the combination gel as well as formulation stability and tolerability data that are potentially clinically relevant.     

Impact of a fixed combination of clindamycin phosphate 1.2%-benzoyl peroxide 2.5% aqueous gel on health-related quality of life in moderate to severe acne vulgaris

The acne-specific quality of life (Acne-QoL) questionnaire was developed to measure the impact of facial acne across 4 domains (acne symptoms, role-emotional, self-perception, role-social) of health-related quality of life (HRQL). This analysis assessed the impact of clindamycin phosphate 1.2%-benzoyl peroxide 2.5% (clindamycin-BPO 2.5%) gel on HRQL in a combined study population (N = 2813) of participants with moderate to severe acne vulgaris. Although the results presented within do not include factors of study and study-by-treatment interaction, analyses were performed to confirm that the results were consistent across the 2 identical, double-blind, randomized studies and within each treatment group across studies to justify pooling the data from both studies. The Acne-QoL questionnaire was administered at baseline and at the end of treatment (week 12). Treatment with clindamycin-BPO 2.5% gel significantly improved participant-reported HRQL across all 4 domains compared with individual active ingredients and vehicle (P < .001). The percentage improvement in mean Acne-QoL domain scores with clindamycin-BPO 2.5% gel ranged from 37% to 59%. Because the negative impact of facial acne on HRQL is one of the primary motivators for patients to seek treatment, this analysis underscores the importance of physicians incorporating assessments of HRQL into their clinical decision making.     

Efficacy of the fixed 1.2% clindamycin phosphate, 0.025% tretinoin gel formulation (Velac®) and a proprietary 0.025% tretinoin gel formulation (Aberela®) in the topical control of facial acne

Background A formulation containing agents affecting the non-inflammatory as well as the inflammatory lesions of acne vulgaris at the same time would be efficient, probably showing a high efficacy and possibly a considerable shortening of the duration of treatment. One single formulation would simplify drug administration thereby enhancing patient compliance and possibly leading to improved therapeutic results. In two studies this seems to have been corroborated for the fixed clindamycin phosphate-tretinoin gel formulation. Objective This study was designed to assess whether the recently developed fixed formulation of 1.2% clindamycin phosphate and 0.025% tretinoin in a gel base (Velac®), further referred to as Clindamycin phosphate Tretinoin Gel is at least as effective as a proprietary 0.025% tretinoin gel formulation (Aberela®, Janssen Cilag Ab, Sollentuna, Sweden; further defined as tretinoin) showing an additional anti-inflammatory effect in the treatment of moderate to severe acne vulgaris. Methods In a double-blind, randomised study 72 patients were treated with CTG and 73 with tretinoin gel in a once daily regimen for 12 weeks. Responses, irritation as well as possible systemic and other adverse effects were recorded after 4, 8 and 12 weeks of treatment and the improvement, compared to baseline, assessed in all included patients. An additional assessment of the safety parameters was carried out at week 2. Parameters of efficacy were the various acne lesion counts, the overall acne severity grade and the calculated totals of acne lesion counts. Results CTG was statistically significantly more effective than tretinoin at the P= 0.05 level in the papular and the total mean inflammatory lesion counts as well as in the estimated or calculated mean overall acne severity scores. CTG and tretinoin gel were equally effective in the remaining parameters: open and closed comedones, the calculated total mean comedone, the pustule as well as the nodule lesion counts. The onset of action was faster for CTG than for tretinoin gel and evident in all assessed parameters except in open comedone lesion counts. In the calculated total mean acne lesion counts, half of all acne lesions had disappeared by week 6 of treatment with CTG, whereas this was recorded at week 9 for tretinoin gel. No clinically relevant changes in the parameters of safety as a consequence of treatment were observed, although the burning component of irritation was shown to be significantly less for CTG than for tretinoin gel. The observed adverse effects were considered minor. Treatment had to be discontinued in five patients on CTG and three on tretinoin. Conclusion The addition of clindamycin to tretinoin, as in CTG, enhances the comedolytic efficacy of tretinoin in moderate to severe acne of the face, maintaining at the same time its anti-inflammatory efficacy thus accelerating resolution of all types of acne lesions without affecting the safety of response to both components.     

Clindamycin phosphate 1.2%/benzoyl peroxide 3% fixed‐dose combination gel versus topical combination therapy of adapalene 0.1% gel and clindamycin phosphate 1.2% gel in the treatment of acne vulgaris in Japanese patients: A multicenter,randomized, investigator‐blind,parallel‐group study

Adapalene 0.1% (ADA) with clindamycin phosphate 1.2% (CLNP; ADA + CLNP) and the fixed‐dose combination containing CLNP and benzoyl peroxide 3% (CLNP/BPO 3%) are strongly recommended for the early treatment of acne vulgaris in Japan. Here, we compare the early efficacy and safety of CLNP/BPO 3% with Japanese standard topical use of ADA + CLNP in the treatment of acne vulgaris. In this phase IV, multicenter study, 351 patients were randomized to receive CLNP/BPO 3% or ADA + CLNP for 12 weeks. The primary end‐point was percentage change from baseline in total lesion (TL) counts at week 2. Secondary end‐points included the percentage change from baseline in TL, inflammatory and non‐inflammatory lesion (IL and non‐IL) counts, Investigator's Static Global Assessment (ISGA), quality of life (QoL [Skindex‐16]) and patient preference. Local tolerability scores and adverse events were also recorded. CLNP/BPO 3% provided a significantly greater percentage reduction from baseline in TL compared with ADA + CLNP at week 2, and week 4. Compared with ADA + CLNP, CLNP/BPO 3% was superior at reducing IL (but not non‐IL) over weeks 2–12, was more effective at improving patient QoL and ISGA, and scored higher in patient‐preference assessments. Both treatments were well tolerated; adverse drug reactions occurred more frequently in patients receiving ADA + CLNP (37%) than in those receiving CLNP/BPO 3% (17%). In conclusion, CLNP/BPO 3% showed greater efficacy for the early treatment of acne vulgaris in Japan, with a more favorable safety profile compared with ADA + CLNP.     

低浓度过氧化苯甲酰凝胶治疗寻常痤疮的观察

确定新一代低浓度的过氧化苯甲酰凝胶产品班赛凝胶,对初治或近期复发的寻常痤疮患者的疗效和安全性,探讨更有效、依从性好的治疗方法。本组研究采用开放观察方法。药物每天外用2次,连续用8周。皮损按实际计数,疗前计数为基础,治疗后2周、4周、8周随访分别计数与基础值比较,并记录不良反应,评估疗效和安全性。结果29例寻常痤疮患者完成观察,显示低浓度的过氧化苯甲酰凝胶对初治或近期复发的寻常痤疮患者的丘疹、脓疱、白头粉刺和黑头粉刺皮损均有效。不良反应轻微,均能耐受。低浓度的过氧化苯甲酰凝胶对初始或近期复发的轻、中度寻常痤疮的炎症与非炎症性皮损的患者疗效好,安全,患者依从性好。     

低浓度对氧化苯甲酰凝胶治疗寻常痤疮的观察

确定新一代低浓度的氧化苯甲酰凝胶产品班赛凝胶，对初治或近期复发的寻常痤疮患者的疗效和安全性，探讨更有效、依从性好的治疗方法。本组研究采用开放观察方法。药物每天外用2次，连续用8周。皮损实际计数，疗前计数为基础，治疗后2周、4周、8周随访分别数与基础值比较，并记录不良反应，评估疗效和安全性。结果29例寻常痤疮患者完成观察，显示低浓度的过氧化苯甲酰凝胶对初治或近期得发的寻常痤疮患者的丘疹、脓疱、白头粉刺和黑头粉刺皮损均有效。不良反应轻微，均能耐受。低浓度的过氧化苯甲酰凝胶对初始或近期复发的轻、中度寻常痤疮的炎症与非炎症性皮损的患者疗效好，安全，患者依从性好。     

Comparison of topical clindamycin phosphate, benzoyl peroxide, and a combination of the two for the treatment of acne vulgaris

Patients with moderate to severe acne vulgaris were treated for 10 weeks with either topical clindamycin phosphate (1% solution) twice daily, benzoyl peroxide (5% gel) twice daily, or benzoyl peroxide (5% gel) in the morning and clindamycin phosphate (1% solution) in the evening. The effects of each regimen appeared to vary in decreasing specific types of acne lesions, with the combination therapy showing the greatest decrease when all types of lesions were considered. Cutaneous side-effects were greatest with benzoyl peroxide alone during the early weeks of treatment, while the combination therapy displayed no greater incidence of redness, scaling, or itching than clindamycin phosphate alone. All three regimens produced clinical improvements which did not differ significantly from each other.     

Efficacy of the addition of salicylic acid to clindamycin and benzoyl peroxide combination for acne vulgaris

Clindamycin phosphate (CDP), benzoyl peroxide (BPO) and salicylic acid (SA) are known to be effective acne therapy agents depending on their anti-inflammatory and comedolytic properties. The purpose of this study was to investigate the efficacy and tolerability of the addition of SA treatment to CDP and BPO (SA and CDP + BPO) and compare it with CDP + BPO in patients with mild to moderate facial acne vulgaris. Forty-nine patients were enrolled in a 12 week prospective, single-blind, randomized, comparative clinical study. Efficacy was assessed by lesion counts, global improvement, quality of life index and measurements of skin barrier functions. Local side effects were also evaluated. Both combinations were effective in reducing total lesion (TL), inflammatory lesion (IL) and non-inflammatory lesion (NIL) counts. There were statistically significant differences between treatment groups for reductions in NIL counts beyond 2 weeks, IL counts and TL counts throughout the all study weeks, and global improvement scores evaluated by patients and investigator at the end of the study in favor of SA and CDP + BPO treatment when compared to CDP + BPO treatment. Both combinations significantly decreased stratum corneum hydration, although skin sebum values decreased with SA and CDP + BPO treatment. These combinations were also well tolerated except significantly higher frequency of mild to moderate transient dryness in patients applied SA and CDP + BPO. The addition of SA to CDP + BPO treatment demonstrated significantly better and faster results in terms of reductions in acne lesion counts and well tolerated except for higher frequency of mild to moderate transient dryness.