Objective and self-reported evidence of dextromethorphan antitussive efficacy in children, aged 6-11 years, with acute cough due to the common cold.

Objective: To determine objective and subjective endpoints most suitable for evaluating antitussive efficacy of dextromethorphan hydrobromide (DXM) in children. Spontaneous resolution of acute cough and large placebo effects are impediments to evaluating antitussive efficacy. Another impediment is paucity of age-appropriate, validated cough assessment tools.

Randomized, double-blind, noninferiority study of diclofenac diethylamine 2.32% gel applied twice daily versus diclofenac diethylamine 1.16% gel applied four times daily in patients with acute ankle sprain.

Background: Diclofenac diethylamine (DDEA) gel has demonstrated efficacy for treatment of ankle sprains in both the 1.16% four-times-daily (QID) and 2.32% twice-daily (BID) formulations.

Assessing the bioequivalence of over-the-counter esomeprazole banded capsules and multiple-unit pellet system tablets .

Objective: To demonstrate bioequivalence between two esomeprazole formulations under fasted and fed conditions.

Materials: Esomeprazole 20 mg multiunit pellet system (test; MUPS) tablets and over-the-counter esomeprazole 20 mg banded capsules (reference).

Materials And Methods: This open-label, randomized, 6-period crossover study assigned healthy males and females to receive single doses of each study drug under fasted or fed conditions.

Efficacy and safety of twice daily sustained-release paracetamol formulation for osteoarthritis pain of the knee or hip: a randomized, double-blind, placebo-controlled, twelve-week study.

Objective: Evaluate efficacy and safety of an investigational, twice daily sustained-release (SR) paracetamol formulation in subjects with knee or hip osteoarthritis (OA).

Methods: In this multicenter, double-blind, parallel study (NCT02311881), subjects with hip or knee OA were randomly assigned to SR paracetamol 2 × 1000 mg BID, extended-release (ER) paracetamol 2 × 665 mg TID or placebo for 12 weeks. Primary endpoint was mean change from baseline through 12 weeks in WOMAC Osteoarthritis Index pain.

Diclofenac systemic bioavailability of a topical 1% diclofenac + 3% menthol combination gel vs. an oral diclofenac tablet in healthy volunteers: a randomized, open-label, crossover study .

Objective: Evaluate systemic exposure with repeated topical application of a fixed-combination topical gel product containing 1% diclofenac sodium and 3% menthol in either of 2 formulation packages relative to oral administration.

Methods: In this phase 1, single-center, 4-way crossover study, healthy volunteers aged 18 - 50 years underwent consecutive 3-day treatment regimens in a randomly assigned sequence with each of 4 treatment groups: 4 g of topical 1% diclofenac + 3% menthol gel administered via an aluminum tube or roll-on device applied 4 times daily; 4 g of topical 1% diclofenac sodium gel (Voltaren Gel) applied 4 times daily; and oral diclofenac sodium tablets 50 mg 3 times daily. Treatment regimens were separated by 2-day washout periods.

Pharmacokinetics and Safety of Valganciclovir in Pediatric Heart Transplant Recipients 4 Months of Age and Younger.

Background: Valganciclovir (VGCV) effectively prevents cytomegalovirus disease in adult and pediatric solid organ transplant recipients. A dosing algorithm for VGCV for pediatric patients, based on body surface area and renal function, provides a personalized dose using age-appropriate formulations. The suitability of this dosing algorithm has not been assessed specifically in infants and neonates 4 months of age and younger receiving a solid organ transplant.

The effect of mild to moderate renal impairment on the pharmacokinetics of the nucleoside analog hepatitis C virus polymerase inhibitor mericitabine.

Mericitabine is the prodrug of RO4995855, a selective inhibitor of the hepatitis C virus (HCV) NS5B polymerase. This study assessed the effect of renal impairment on RO4995855 pharmacokinetics. In this open-label study, HCV-negative volunteers (18-75 years) with normal renal function (NRF: creatinine clearance [CLCR ] >80 mL/min, n = 10) or stable renal impairment (mild: CLCR 50-80 mL/min, n = 10; moderate: CLCR 30-49 mL/min, n = 10) received oral mericitabine 1000 mg twice daily (BID) (500 mg BID for moderate renal impairment) for 5 days.

Understanding the effect of the HCV polymerase inhibitor mericitabine on early viral kinetics in the phase 2 JUMP-C and PROPEL studies.

Aims: The aim was to evaluate early viral kinetics in patients receiving mericitabine [hepatitis C virus (HCV) nucleoside polymerase inhibitor] with peginterferon alfa-2a (40KD) and ribavirin in two clinical trials (PROPEL and JUMP-C).

Methods: We examined rapid virological responses (RVRs; week 4 HCV RNA <15 IU ml(-1) ) and complete early virological responses (cEVR; week 12 HCV RNA <15 IU ml(-1) ) in HCV genotype 1/4-infected patients receiving mericitabine (500 or 1000 mg) or placebo twice daily plus peginterferon alfa-2a and ribavirin.

Results: Among IL28B rs12979860 CC genotype patients receiving 500 or 1000 mg mericitabine or placebo, respectively, RVR rates were 64.

Effect of meal and antisecretory agents on the pharmacokinetics of danoprevir/ritonavir in healthy volunteers.

Objectives: To evaluate the effect of a low- and high-fat meal and co-administration of ranitidine or omeprazole on the pharmacokinetics of ritonavir-boosted danoprevir (DNVr).

Methods: In this randomised, open-label, cross-over study, healthy subjects received a single dose of DNVr. In group 1, DNVr was administered while fasting or with a low-fat or high-fat meal.

Single-dose pharmacokinetics of the HCV polymerase inhibitor mericitabine in healthy Caucasian and Japanese subjects.

To investigate the pharmacokinetics of mericitabine in healthy Caucasian and Japanese subjects, healthy Caucasian (n = 32) and Japanese (n = 32) subjects were randomized to receive single 500, 1,000, or 2,000 mg doses of mericitabine or a placebo, after which plasma and urine samples were collected for 72 h. Mericitabine (prodrug), RO4995855 (parent), and RO5012433 (uridine metabolite) concentrations were quantified by tandem mass spectrometry. Pharmacokinetics were estimated by non-compartmental methods, and pharmacokinetic parameters of RO4995855 were normalized by body weight.

Effect of ritonavir-boosted danoprevir, a potent hepatitis C virus protease inhibitor, on the pharmacokinetics of methadone in healthy subjects undergoing methadone maintenance therapy.

Study Objective: To investigate the steady-state pharmacokinetics of methadone when coadministered with ritonavir-boosted danoprevir (DNVr).

Design: Open-label, two-period, single-sequence pharmacokinetic study.

Setting: Two U.

Pharmacokinetics of a three-way drug interaction between danoprevir, ritonavir and the organic anion transporting polypeptide (OATP) inhibitor ciclosporin.

Background: Danoprevir (RG7227) is a potent macrocyclic inhibitor of the hepatitis C virus NS3/4A protease, which is currently in development in combination with low-dose ritonavir for the treatment of chronic hepatitis C infection. Danoprevir is a substrate of cytochrome P450 3A4, and the organic anion transporting polypeptides (OATP) 1B1 and 1B3.

Objective: The objective of this study was to evaluate the effect of a potent OATP inhibitor, ciclosporin, on danoprevir pharmacokinetics, when administered as danoprevir/ritonavir.

Improved human bioavailability of vemurafenib, a practically insoluble drug, using an amorphous polymer-stabilized solid dispersion prepared by a solvent-controlled coprecipitation process.

The present work deals with improving the solubility of vemurafenib, a practically insoluble drug, by converting it into an amorphous-solid dispersion using a solvent-controlled precipitation process. The dispersion containing vemurafenib and hypromellose acetate succinate (HPMCAS), an enteric polymer, is termed microprecipitated bulk powder (MBP), in which the drug is uniformly dispersed within the polymeric substrate. HPMCAS was found to be the most suitable polymer for vemurafenib MBP, among a series of enteric polymers based on superior physical stability and drug-release characteristics of the MBP.