Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The clinical program for AMELUZ included three double-blind and placebo-controlled phase 3 trials (Trials 1, 2, and 3), enrolling a total of 299 subjects that were treated with narrow band light. Trial subjects were adults greater than or equal to 49 years of age, and the majority had Fitzpatrick skin type I, II, or III. No subjects had Fitzpatrick skin type V or VI. Approximately 86% of subjects were male, and all subjects were White.

For all three phase 3 trials, the enrolled subjects had mild to moderate AKs (Olsen grade 1 and 2) with 4 to 8 lesions on the face and scalp. Overall, 212 AMELUZ-treated subjects (n=32, n=55, and n=125) and 87 subjects receiving placebo (n=16, n=32, n=39) were illuminated with BF-RhodoLED or similar narrow spectrum lamps. For these trials, the maximal dose was one tube of AMELUZ (2 g) and the size of the application area was up to 20 cm2.

Local skin reactions at the application site were observed in about 99.5% of subjects treated with AMELUZ and narrow spectrum lamps. The most frequent adverse reactions during and after PDT were application site erythema, pain, burning, irritation, edema, pruritus, exfoliation, scab, induration, and vesicles.

Most adverse reactions occurred during illumination or shortly afterwards, were generally of mild or moderate intensity, and lasted for 1 to 4 days in most cases; in some cases, however, they persisted for 1 to 2 weeks or even longer. Severe pain/burning occurred in up to 30% of subjects. In one case, the adverse reactions required interruption or discontinuation of the illumination.

Table 1 presents the incidence of common (≥1%, <10%) and very common (≥10%) adverse reactions at the application site in randomized, multicenter trials which evaluated a maximal dose of one tube of AMELUZ (2 g) and an application area up to 20 cm2.

Common (≥1%, <10%) adverse reactions not at the application site for AMELUZ maximal dose of one tube (2 g) and application area up to 20 cm2 were headache, skin exfoliation, chills and eyelid edema.

Less common (≥0.1%, <1%) adverse reactions at the application site for AMELUZ maximal dose of one tube (2 g) and application area up to 20 cm2 were hemorrhage and swelling. The adverse reactions not at the application site were blister, feeling hot, pruritus, pyrexia, scab, nervousness, pain, petechiae, rash pustular, skin erosion and ulcer.

In a clinical trial designed to investigate the sensitization potential of aminolevulinic acid with 216 healthy subjects, 13 subjects (6%) developed allergic contact dermatitis after continuous exposure for 21 days with doses of aminolevulinic acid that were higher than doses normally used in the treatment of AK.

In two open label clinical trials to evaluate safety and tolerability, 116 subjects with actinic keratosis (AK) on the face and scalp were treated with three tubes (6 g) of AMELUZ applied to a 60 cm² area. Most adverse reactions observed were consistent with those reported in trials using one tube (2 g) of AMELUZ on a 20 cm² area (see Table 1). Additional reactions which occurred in ≥1% of subjects when three tubes (6 g) of AMELUZ were applied to a 60 cm² area included dry eyes, photosensitivity, and application site discoloration, dryness, papules, and fissures.

The frequencies of certain adverse reactions at the application site in these trials—exfoliation, itching, scabbing, and erosion—were more than 10% higher with the larger dose (three tubes, 6 g) and treatment area (60 cm²) compared to the frequencies observed in the trials for the smaller dose (one tube, 2 g) and area (20 cm²). Severe application site pain was reported by 41% of the subjects treated with three tubes (6 g) on a 60 cm² area. Most cases were reported during PDT illumination. A total of 15% of subjects discontinued illumination due to adverse reactions.