Tafenoquine exposure assessment, safety, and relapse prevention efficacy in children with Plasmodium vivax malaria: open-label, single-arm, non-comparative, multicentre, pharmacokinetic bridging, phase 2 trial.

Background: Single-dose tafenoquine 300 mg is approved for Plasmodium vivax malaria relapse prevention in patients at least 16 years old. We aimed to determine appropriate oral tafenoquine paediatric dosing regimens, including a dispersible formulation, and evaluated tafenoquine efficacy and safety in children infected with P vivax.

Methods: This open-label, single-arm, non-comparative, multicentre, pharmacokinetic bridging, phase 2 study enrolled children (2-15 years) who weighed 5 kg or more, with glucose-6-phosphate dehydrogenase activity more than 70% of the local population median, and P vivax malaria infection, from three community health centres in Vietnam and one in Colombia.

Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers.

Introduction: Tafenoquine has been recently registered for the prevention of relapse in Plasmodium vivax malaria.

Objective: This study assessed the pharmacodynamic effects of 300-mg single-dose tafenoquine on the retina.

Methods: This phase I, prospective, multicenter, randomized, single-masked, placebo-controlled, parallel-group study was conducted between 2 February 2016 and 14 September 2017 at three US study centers.

Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria.

Background: Tafenoquine, a single-dose therapy for Plasmodium vivax malaria, has been associated with relapse prevention through the clearance of P. vivax parasitemia and hypnozoites, termed "radical cure."

Methods: We performed a phase 3, prospective, double-blind, double-dummy, randomized, controlled trial to compare tafenoquine with primaquine in terms of safety and efficacy.

Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria.

Background: Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed "radical cure"). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax.

Application of the Stable Isotope Label Approach in Clinical Development-Supporting Dissolution Specifications for a Commercial Tablet Product with Tafenoquine, a Long Half-life Compound.

Unlabelled: Bioavailability/bioequivalence studies supporting clinical drug development or commercial supply of drug formulations are often time, cost, and resource intensive. The drug's pharmacokinetic (PK) variability, systemic half-life, and safety issues may pose additional challenges. The stable isotope label (SIL) approach provides a useful tool to significantly reduce the study size in clinical PK studies.

A randomized, double-blind, active-control trial to evaluate the efficacy and safety of a three day course of tafenoquine monotherapy for the treatment of Plasmodium vivax malaria.

Background: Tafenoquine is an investigational 8-aminoquinoline for the prevention of Plasmodium vivax relapse. Tafenoquine has a long half-life and the potential for more convenient dosing, compared with the currently recommended 14-day primaquine regimen.

Methods: This randomized, active-control, double-blind trial was conducted in Bangkok, Thailand.

Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency ( Variant) versus G6PD-Normal Volunteers.

Tafenoquine is an 8-aminoquinoline under investigation for the prevention of relapse in malaria. This open-label, dose-escalation study assessed quantitatively the hemolytic risk with tafenoquine in female healthy volunteers heterozygous for the glucose-6-phosphate dehydrogenase (G6PD)-deficient variant versus G6PD-normal females, and with reference to primaquine. Six G6PD-heterozygous subjects (G6PD enzyme activity 40-60% of normal) and six G6PD-normal subjects per treatment group received single-dose tafenoquine (100, 200, or 300 mg) or primaquine (15 mg × 14 days).

Pharmacokinetic Interactions between Tafenoquine and Dihydroartemisinin-Piperaquine or Artemether-Lumefantrine in Healthy Adult Subjects.

Tafenoquine is in development as a single-dose treatment for relapse prevention in individuals with Plasmodium vivax malaria. Tafenoquine must be coadministered with a blood schizonticide, either chloroquine or artemisinin-based combination therapy (ACT). This open-label, randomized, parallel-group study evaluated potential drug interactions between tafenoquine and two ACTs: dihydroartemisinin-piperaquine and artemether-lumefantrine.

An early pregnancy HbA1c ≥5.9% (41 mmol/mol) is optimal for detecting diabetes and identifies women at increased risk of adverse pregnancy outcomes.

Objective: Pregnant women with undiagnosed diabetes are a high-risk group that may benefit from early intervention. Extrapolating from nonpregnancy data, HbA1c ≥6.5% (48 mmol/mol) is recommended to define diabetes in pregnancy.

Tafenoquine at therapeutic concentrations does not prolong Fridericia-corrected QT interval in healthy subjects.

Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subjects aged 18-65 years were randomized to one of five treatment groups (n = 52 per group) to receive placebo, tafenoquine 300, 600, or 1200 mg, or moxifloxacin 400 mg (positive control).

Adjusting for covariates in non-inferiority studies with margins defined as risk differences.

Adjusting for covariates makes efficient use of data and can improve the precision of study results or even reduce sample sizes. There is no easy way to adjust for covariates in a non-inferiority study for which the margin is defined as a risk difference. Adjustment is straightforward on the logit scale, but reviews of clinical studies suggest that the analysis is more often conducted on the more interpretable risk-difference scale.

Pharmacokinetics of oral sitamaquine taken with or without food and safety and efficacy for treatment of visceral leishmaniais: a randomized study in Bihar, India.

This randomized, open-label study of patients in India with visceral leishmaniasis (VL) investigated the effect of food on sitamaquine and desethyl-sitamaquine pharmacokinetics. Patients were randomized to receive oral sitamaquine, 2 mg/kg/day, once a day for 21 days across four cohorts (n = 41) (fasted/fed, fed/fasted, fed/fed, and fasted/fasted) over two periods (days 1-10 and 11-21), or intravenous amphotericin B (AmB), 1 mg/kg every other day for 30 days (n = 20). Mean day 21 pharmacokinetics across the four cohorts were sitamaquine, area under curve (AUC)((0-τ)) = 6,627-8,903 ng.

Functional outcome after total knee arthroplasty revision: a meta-analysis.

The objective of this study was to perform a systematic literature review to describe patient outcome after total knee arthroplasty revision procedures using various global knee score ratings. English language articles published from 1966 through 2000 were identified through a computerized literature search and bibliography review. A multistage assessment was used to determine the articles containing data that could meet our objective.