Single and multiple i.m. injections of RPV LA demonstrated favourable local/systemic tolerability in healthy volunteers. RPV pharmacokinetics suggested that clinically relevant plasma concentrations can be achieved with this LA formulation.

Domperidone effects on QTc duration were assessed in a single-center, double-blind, four-way crossover study of 44 healthy participants randomized to one of four treatment sequences consisting of four treatment periods separated by 4–9 days washout. On Day 1 of each 4-day period, participants began oral domperidone 10 or 20 mg q.i.d., matching placebo q.i.d., or single-dose moxifloxacin 400 mg (positive control)/placebo q.i.d. In each period, triplicate 12-lead electrocardiograms were recorded at baseline (30, 20, and 10 minutes predose), 8 timepoints after dosing on Days 1 and 4, and predose on Day 4. In mixed effects models, the largest difference for domperidone in least squares means for change from baseline QTcP versus placebo was 3.4 milliseconds (20 mg q.i.d., Day 4), 90% CI: 1.0–5.9, and <10 milliseconds at all timepoints for both domperidone dosages. Moxifloxacin response confirmed assay sensitivity. Participants achieved expected domperidone plasma exposures. No significant exposure-response relationship was found for QTc increase per ng/mL domperidone (90% CI of the slope estimate included zero at mean Cmax on Day 1 or Day 4). In summary, domperidone at doses up to 80 mg/day did not cause clinically relevant QTc interval prolongation.

Background Both the elderly and individuals with comorbidities are at increased risk of developing influenza-related complications. Novel influenza antivirals are required, given limitations of current drugs (eg, resistance emergence and poor efficacy). Pimodivir is a first-in-class antiviral for influenza A under development for these patients. Methods Hospitalized patients with influenza A infection were randomized 2:1 to receive pimodivir 600 mg plus oseltamivir 75 mg or placebo plus oseltamivir 75 mg twice daily for 7 days in this phase 2b study. The primary objective was to compare pimodivir pharmacokinetics in elderly (aged 65–85 years) versus non-elderly adults (aged 18–64 years). Secondary endpoints included time-to-patient-reported symptom resolution. Results Pimodivir pharmacokinetic parameters in non-elderly and elderly patients were similar. Time-to-influenza symptom resolution was numerically shorter with pimodivir (72.45 hours) than placebo (94.15 hours). There was a lower incidence of influenza-related complications in the pimodivir group (7.9%) versus placebo group (15.6%). Treatment was generally well tolerated. Conclusions No apparent relationship was observed between pimodivir pharmacokinetics and age. Our data demonstrate the need for a larger study of pimodivir in addition to oseltamivir to test whether it results in a clinically significant decrease in time-to-influenza symptom alleviation and/or the frequency of influenza complications.

Combination treatment with pimodivir and oseltamivir in healthy volunteers showed no clinically relevant drug-drug interactions. No safety concerns were identified with pimodivir 600 mg twice daily alone or in combination with oseltamivir 75 mg twice daily.