a TKL Research, Inc. , Fair Lawn , NJ , USA.
b Formerly Foamix Pharmaceuticals, Inc. (Ret.) , Bridgewater , NJ , USA.
J Immunotoxicol. 2019 Dec;16(1):133-139. doi: 10.1080/1547691X.2019.1610117.
FMX101 4% contains 4% micronized minocycline (as an HCl) formulated in a lipophilic foam vehicle for topical administration. FMX101 4% has been shown to be an effective and well-tolerated treatment for moderate-to-severe acne in three Phase 3 pivotal studies, however, skin sensitization and toxicity potential remains to be fully evaluated. Four single-center, randomized, controlled, within-subject comparison studies were conducted to evaluate the potential for phototoxicity, photoallergy, skin sensitization, and cumulative skin irritation with topical administration of FMX101 4% and the corresponding vehicle. Across the four studies, healthy male and non-pregnant female volunteers (age ≥18 years) were randomized to FMX101 4%, vehicle, or other controls. In the phototoxicity study, treated skin was irradiated at 3 and 24 hr post-application, and local tolerability was assessed pre- and post-irradiation. In the photoallergy study, the skin was treated and irradiated (post-24 hr) twice weekly for 3 wk (induction phase), rested for 10-17 d, and naive skin sites were treated and irradiated (challenge phase); skin reactions were assessed after patch removal and post-irradiation. In the sensitization study, the skin was treated for 3 wk (induction phase), then rested for 10-14 d, and naive skin sites were treated for 48 hr (challenge phase); contact sensitization was assessed for both phases. In the cumulative irritation study, treatment and vehicle were applied daily for 21 d; skin irritation was assessed after each application. In all studies, standard safety assessments were conducted. A total of 32, 56, 233, and 42 subjects were enrolled in the phototoxicity, photoallergy, sensitization, and skin irritation studies, respectively. There was no evidence of phototoxicity, photoallergy, skin sensitization, or skin irritation potential with FMX101 4%. Few adverse events, mostly mild to moderate, were reported. In conclusion, FMX101 4% appeared to be well tolerated and non-irritating, and was considered to be non-sensitizing, non-phototoxic, and non-photoallergic.
FMX101 4% 含有 4%的米诺环素（盐酸盐），制成亲脂性泡沫载体，用于局部给药。在三项 III 期关键研究中，FMX101 4% 已被证明是一种有效且耐受性良好的中重度痤疮治疗药物，然而，皮肤致敏和毒性潜力仍需充分评估。进行了四项单中心、随机、对照、自身对照研究，以评估局部给予 FMX101 4%及其相应载体的光毒性、光过敏、皮肤致敏和累积皮肤刺激的潜力。在四项研究中，健康的男性和非妊娠女性志愿者（年龄≥18 岁）被随机分配到 FMX101 4%、载体或其他对照。在光毒性研究中，在应用后 3 小时和 24 小时照射处理皮肤，并在照射前后评估局部耐受性。在光过敏研究中，皮肤每周处理和照射两次（诱导期），共 3 周；休息 10-17 天，并用处理和照射未处理皮肤（挑战期）；去除贴片后和照射后评估皮肤反应。在致敏研究中，皮肤处理 3 周（诱导期），然后休息 10-14 天，并用处理 48 小时（挑战期）处理未处理皮肤；评估两个阶段的接触致敏。在累积刺激研究中，每日处理和涂抹药物 21 天；每次应用后评估皮肤刺激。在所有研究中，均进行了标准安全性评估。共有 32、56、233 和 42 名受试者分别参加了光毒性、光过敏、致敏和皮肤刺激研究。FMX101 4% 无光毒性、光过敏、皮肤致敏或皮肤刺激潜力的证据。报告的不良事件很少，大多为轻度至中度。总之，FMX101 4% 似乎耐受性良好，无刺激性，被认为是非致敏、非光毒性和非光过敏的。
