Drug Therapy

Clindamycin Phosphate–Tretinoin Combination Gel Revisited: Status Report on a Specific Formulation Used for Acne Treatment

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What are the clinical data evaluating the efficacy and tolerability/safety of the specific aqueous-based gel formulation of CP-Tret?

An aqueous-based gel formulation (referred to in the literature as a hydrogel) of CP-Tret is devoid of alcohol and contains the excipients described above.14 This formulation was shown to be efficacious, well tolerated, and safe in smaller clinical studies of participants with AV.23,37-39 Two large-scale phase 3 studies were completed (N=2219), powered to compare the efficacy and tolerability/safety of CP-Tret hydrogel (n=634) versus CP hydrogel (n=635), Tret hydrogel (n=635), and vehicle hydrogel (n=315) in participants with facial AV. All 4 study drug formulations in both studies—CP-Tret, CP, Tret, vehicle—used the same hydrogel vehicle, hereafter referred to simply as gel.16

In both trials, participants 12 years of age and older with AV were randomized to active drug groups versus vehicle (2:2:2:1 randomization), each applied once daily at bedtime for 12 weeks.16 The baseline demographics among all 4 study groups were well matched, with approximately two-thirds of white participants and one-third Asian (2%–3%), black (19%–21%), or Hispanic (9%–10%). Approximately half of enrolled participants were 16 years of age or younger (mean age [range], 19.0–20.2 years). Enrolled participants in each study group presented at baseline predominantly with facial AV of mild (grade 2 [20%–23% of enrolled participants]) or moderate (grade 3 [60%–62% of enrolled participants]) severity based on a protocol-mandated, 6-point investigator static global assessment scale. Investigator static global assessment scores and acne lesion counts, including noninflammatory (comedonal), inflammatory (papules, pustules), and total AV lesions, were evaluated at baseline and weeks 2, 4, 8, and 12 (end of study [EOS]). Among the 4 study groups at baseline, the range of mean lesion counts was 27.7 to 29.3 for noninflammatory lesions, 26.0 to 26.4 for inflammatory lesions, and 76.4 to 78.3 for total lesions. All enrolled participants met protocol-mandated, standardized, inclusion, exclusion, and prestudy washout period criteria.16

The primary efficacy end points determined based on intention-to-treat analysis were the percentage reduction in all 3 lesion counts at EOS compared to baseline and the proportion of participants who achieved scores of clear (grade 0) or almost clear (grade 1) at EOS. The secondary end point parameter was time to 50% reduction in total lesion counts.16

The study efficacy outcomes were as follows: The mean percentage reduction in inflammatory lesions at EOS versus baseline was significantly higher in the CP-Tret group than in each of the other 3 groups (CP-Tret, 53.4%; CP, 47.5%; Tret, 43.3%; vehicle, 30.3%)(P<.005).16 The mean percentage reduction in noninflammatory lesions at EOS versus baseline was significantly higher in the CP-Tret group than in each of the other 3 groups (CP-Tret, 45.2%; CP, 31.6%; Tret, 37.9%; vehicle, 18.5%)(P≤.0004). The mean percentage reduction in total AV lesions at EOS versus baseline was significantly higher in the CP-Tret group than in each of the other 3 groups (CP-Tret, 48.7%; CP, 38.3%; Tret, 40.3%; vehicle, 23.2%)(P≤.0001). The median time to 50% reduction in total AV lesion counts was significantly faster with CP-Tret (8 weeks) compared to the other 3 groups (CP, 12 weeks [P<.0001]; Tret, 12 weeks [P<.001]; vehicle, not reached by EOS [P<.0001]). The consistency of results, methodologies, and overall study characteristics between the 2 phase 3 RCTs allowed for accurate pooling of data.16

Tolerability and safety assessments were completed at each visit for all enrolled participants. No adverse events (AEs) were noted in approximately 90% of enrolled participants.16 The most common AEs noted over the course of the study were mild to moderate application-site reactions (eg, dryness, erythema, burning, pruritus, desquamation), mostly correlated with the 2 groups containing tretinoin—CP-Tret and Tret—which is not unanticipated with topical retinoid use; 1.2% of these participants withdrew from the study due to such application-site AEs. No serious AEs or systemic safety signals emerged during the study.16

What summarizing statements can be made about CP-Tret gel from these study results that may be helpful to clinicians treating patients with AV?

The gel formulation of CP-Tret incorporates active ingredients that target different pathophysiologic cascades in AV, providing antimicrobial, anti-inflammatory, and anticomedonal effects.

Applied once daily, CP-Tret gel demonstrated the ability to achieve complete or near-complete clearance of comedonal and papulopustular facial AV lesions of mild to moderate severity in approximately 40% of participants within 12 weeks of use in 2 large-scale RCTs.16 The ability to achieve a median 50% reduction in total lesions by 8 weeks of use provides relevant information for patients regarding reasonable expectations with therapy.

The favorable cutaneous tolerability profile and low number of AEs demonstrated with CP-Tret gel are major considerations, especially as skin tolerability reactions can impede patient adherence with treatment. Any issues that interfere with achieving a favorable therapeutic outcome can lead to patients giving up with their therapy.

The large number of patients with skin of color treated with CP-Tret gel (n=209) in the 2 phase 3 RCTs is important, as the spectrum of racial origins, skin types, and skin colors seen in dermatology practices is diversifying across the United States. Both clinicians and patients with skin of color are often concerned about the sequelae of medication-induced skin irritation, which can lead to ensuing dyschromia.

Concerns related to potential development of clindamycin-resistant P acnes with CP-Tret gel may be addressed by concurrent use of BP, including with leave-on or short-contact therapy.

Although phase 3 RCTs evaluate therapeutic agents as monotherapy, in real world clinical practice, combination topical regimens using different individual products are common to optimize therapeutic outcomes. Advantages of the CP-Tret gel formulation, if a clinician desires to use it along with another topical product, are once-daily use and the low risk for cutaneous irritation.

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