The lidocaine/tetracaine patch provided effective anaesthesia with an application time as short as 10 min and was better than lidocaine/prilocaine cream at all application times shorter than 60 min, demonstrating a substantial improvement in time to onset of anaesthesia. The lidocaine/tetracaine patch provided an important alternative to lidocaine/prilocaine cream for topical local anaesthesia.

The pharmacokinetics, pharmacodynamics, tolerability, and food effect of cenerimod, a potent sphingosine-1-phosphate subtype 1 receptor modulator, were investigated in three sub-studies. Two double-blind, placebo-controlled, randomised studies in healthy male subjects were performed. Cenerimod was administered either as single dose (1, 3, 10 or 25 mg; Study 1) or once daily for 35 days (0.5, 1, 2 or 4 mg; Study 2). A two-period cross-over, open-label study was performed to assess the food effect (1 mg, Study 3). The pharmacokinetic profile of cenerimod was characterised by a tmax of 5.0–6.2 h. Terminal half-life after single and multiple doses ranged from 170 to 199 h and 283 to 539 h, respectively. Food had no relevant effect on the pharmacokinetics of cenerimod. A dose-dependent decrease in lymphocyte count was observed after initiation of cenerimod and reached a plateau (maximum change from baseline: −64%) after 20–23 days of treatment. Lymphocyte counts returned to baseline values at end-of-study examination. One serious adverse event of circulatory collapse (25 mg dose group, maximum tolerated dose: 10 mg) and adverse events of mild-to-moderate intensity were reported. Treatment initiation was associated with transient decreases in heart rate and blood pressure at doses >1 and ≥10 mg, respectively.

To evaluate ocular tolerance, healthy volunteers were iontophoresed transclerally using novel OcuPhor trade mark hydrogel drug delivery applicators filled with balanced salt solution. In this three-period crossover study in 24 male and female subjects, 16 subjects received 0 mA and two of the following DC currents: 0.1, 0.5., 1.0, 2.0, 3.0, or 4.0 mA for 20 min; 6 subjects received 3 mA for 20 min and 1.5 mA for 40 min (both equivalent to 60 mAmin total charge). Safety and tolerance were determined by subjective VAS and objective ophthalmic assessments. Subjects were evaluated before and up to 22 hr after dosing. The applicators were well-tolerated and no clinically significant changes in symptomology or in ophthalmic assessments were seen following exposure to 0-3.0 mA for 20 min or 1.5 mA for 40 min. At 4.0 mA 2 of 4 subjects reported a burning sensation under the applicator during dosing which resolved by 22 hr post-dose; superficial changes in fluorescein staining were observed at 1 hr, but not at 22 hr. The OcuPhor trade mark system has promise for noninvasive drug delivery to the eye.

AZD5438 is a novel cyclin-dependent kinase inhibitor with preclinical pharmacodynamic (PD) activity against a range of human tumour xenografts. A first-in-man tolerability and pharmacokinetic (PK) study involving single ascending doses of AZD5438 was conducted in healthy male volunteers. Single oral doses ranging from 5 to 160 mg were studied in 23 subjects. Dose-limiting nausea and vomiting occurred at 160 mg in the absence of prophylactic anti-emetics. The maximum tolerated dose (the dose at which no dose limiting toxicities occurred) was 80 mg, and the maximum well-tolerated dose was deemed to be 60 mg, which was associated with grade1 nausea but no vomiting. Tmax occurred between 0.5-3.0 hours with a relatively short plasma half-life of 1-3 h. The coefficient of variation of exposures within a dose level ranged from 22-71% (AUC) to 16-63% (C max), and exposure increased with increasing dose across the doses studied. <1% of the parent compound was excreted in the urine, suggesting metabolism as the major clearance mechanism. The maximum well-tolerated dose and a number of doses below this level will be taken forward into a PD study using normal tissue biomarkers in humans to determine proof of AZD5438's action on the cell cycle. The pharmacokinetic profile of AZD5438 determined within this study will be used to guide the time-points for PD analysis within the planned PD study.

A series of Phase I studies was conducted in healthy volunteers to examine the systemic bioavailability and safety of topical ozenoxacin. Study 1 examined increasing single doses (relating to quantity and body surface area) of ozenoxacin 1% ointment. Study 2 compared multiple doses of ozenoxacin 1% ointment and placebo applied for 7 days. Study 3 investigated multiple doses of ozenoxacin 2% cream and placebo applied for 7 days. Study 4 examined multiple doses of ozenoxacin 2% cream applied to intact and abraded skin for 8 days. No systemic absorption was observed in any study and ozenoxacin was well tolerated. The most common treatment-related adverse events were application-site reactions (erythema and pruritus), but the differences in local tolerability between ozenoxacin and placebo were not clinically significant.