First-Time-in-Human Study and Prediction of Early Bactericidal Activity for GSK3036656, a Potent Leucyl-tRNA Synthetase Inhibitor for Tuberculosis Treatment.

This first-time-in-human (FTIH) study evaluated the safety, tolerability, pharmacokinetics, and food effect of single and repeat oral doses of GSK3036656, a leucyl-tRNA synthetase inhibitor. In part A, GSK3036656 single doses of 5 mg (fed and fasted), 15 mg, and 25 mg and placebo were administered. In part B, repeat doses of 5 and 15 mg and placebo were administered for 14 days once daily.

A Phase I Study to Show the Relative Bioavailability and Bioequivalence of Fixed-Dose Combinations of Ambrisentan and Tadalafil in Healthy Subjects.

Purpose: Pulmonary arterial hypertension (PAH) is a life-threatening disease that typically causes shortness of breath and exercise intolerance. Combination therapy with ambrisentan and tadalafil has proven to be more effective at preventing clinical failure events in patients with PAH than either drug alone. The aim of this study was to evaluate the bioequivalence of an ambrisentan/tadalafil fixed-dose combination (FDC) compared with co-administration of the 2 monotherapies.

A population analysis of the DGAT1 inhibitor GSK3008356 and its effect on endogenous and meal-induced triglyceride turnover in healthy subjects.

Non-alcoholic steatohepatitis (NASH) is a liver disease in which fatty infiltration is accompanied by liver inflammation. GSK3008356 is under development as a selective inhibitor of diacylglycerol acyltransferase 1 (DGAT1), a key enzyme involved in the formation of triglyceride (TG). Decreased DGAT1 activity can reduce circulating TG and liver TG, and therefore could potentially prevent or treat NASH.

Pharmacokinetics, Safety, and Tolerability Evaluation of Single and Multiple Doses of GSK3342830 in Healthy Volunteers.

This was a first-time-in-human randomized, double-blind, single-center, placebo-controlled dose-escalation study to determine the safety, tolerability, and pharmacokinetic (PK) profiles of GSK3342830 after single and repeat intravenous doses in healthy adult subjects (NCT0271424). Sixty-two subjects were enrolled: 48 subjects in part 1 (single dose) and 14 subjects in part 2 (multiple doses). Following single intravenous infusions, total systemic exposure of GSK3342830 was dose proportional over the 250- to 6000-mg dose range evaluated, whereas peak exposure was approximately dose proportional over the dose range.

Population Pharmacokinetics of Tafenoquine, a Novel Antimalarial.

Tafenoquine is a novel 8-aminoquinoline antimalarial drug recently approved by the U.S. Food and Drug Administration (FDA) for the radical cure of acute malaria, which is the first new treatment in almost 60 years.