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The success of any randomized clinical trial relies on the willingness of people to be recruited in the trial. However, 90% of all clinical trials worldwide have been reported to have failed to recruit the required number of trial participants within the scheduled time. This study aimed to qualitatively explore the motivations and barriers for healthy participants to participate in herbal remedy clinical trials in Tanzania. This study used a qualitative descriptive research design based on the theory of planned behaviour. A total of five Focus Group Discussions (FGD) were conducted at Bagamoyo Clinical Trial Facility from 29 to 30 May 2021. Each group consisted of 5 to 10 participants. The participants of the study were 30 healthy males aged 18 to 45 male who participated in the clinical trial that evaluated the safety, tolerability, and efficacy of Maytenus Senegalensis. The focus group discussions were recorded audio-recorded. Verbatim transcription and thematic analysis were performed on the data. The prominent motivations mentioned were the opportunity for self-development, altruism, flexible study visit schedule, and financial compensation. Furthermore, the Participants' mothers and friends were reported as those most likely to approve of participation in an herbal remedy. The most mentioned barriers were inconvenience related to time commitment requirements, possible side effects, inflexible study visit schedule, and having other commitments. Moreover, the participants' father was reported to be more likely to disapprove of participation in a clinical trial of herbal remedy clinical trial. The results of this study showed that the motivations and barriers of healthy participants to participate in clinical trials of herbal remedies are varied and that participants are motivated by more than financial gains. The identified motivations and barriers can be used as a guideline to improve the design of recruitment and retention strategies for herbal remedy clinical trials.

Global efforts to eliminate onchocerciasis are hampered by the lack of a macrofilaricidal drug capable of killing adult parasites. Oxfendazole, a veterinary anthelminthic, exhibits macrofilaricidal activity and holds promise to shorten treatment durations. Phase 1 studies in healthy Caucasian adults demonstrated favorable pharmacokinetics and safety using a veterinary oral liquid formulation. More recently, a Phase 1 bioavailability trial (NCT04920292) evaluated a field‐applicable tablet formulation in healthy African adults. This study presents a secondary analysis to (i) characterize the population pharmacokinetics of oxfendazole and its major metabolites in healthy African adults receiving the tablet formulation and (ii) propose a dosing regimen for Phase 2 evaluation in patients with onchocerciasis. Thirty healthy African adults were enrolled, and plasma concentration–time profiles of oxfendazole, fenbendazole, and oxfendazole sulfone were obtained from 24 participants who received oxfendazole (8 per dose group: 100 mg single dose, 400 mg single dose, 400 mg once daily for 5 days). All cohorts were pooled and analyzed using nonlinear mixed effects modeling. Oxfendazole absorption was best described by first‐order kinetics with first‐pass metabolism. Dose‐limited bioavailability was evident. Disposition was best described by one‐compartment models with linear elimination. Simulations suggested that 400 mg once daily (or 50 mg twice daily) for 5 days is required to achieve putative exposure targets (> 200 ng/mL for 5 days), with low risk of safety concerns. The population pharmacokinetic model adequately described oxfendazole pharmacokinetics in healthy African adults and supports dosing selection for future clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04920292 Study Highlights What is the current knowledge on the topic? ○Oxfendazole is a veterinary anthelminthic with macrofilaricidal activity against a broad range of parasitic worms. Following a repurposing strategy, it is currently under clinical development for the treatment of human helminth infections, including onchocerciasis. Earlier Phase 1 studies in healthy Caucasian volunteers receiving a liquid formulation showed favorable pharmacokinetics and safety. To support broader use in endemic settings, a field‐adapted tablet formulation was developed. What question did this study address? ○This study characterized the population pharmacokinetic properties of the oxfendazole tablet in healthy African adults and identified suitable dosing regimens for Phase 2 trials in onchocerciasis patients. What does this study add to our knowledge? ○This is the first population pharmacokinetic analysis of oxfendazole in African adults using the tablet formulation. The model incorporated first‐pass metabolism and dose‐limited bioavailability and revealed substantial variability in drug exposure. Simulations suggested that a 400 mg once‐daily or 50 mg twice daily dose of oxfendazole over 5 days is likely to achieve proposed target exposures, with low risk of safety concerns. How might this change drug discovery, development, and/or therapeutics? ○The developed model provides a quantitative basis to guide dose selection of oxfendazole in future clinical trials. Despite variability in exposure and the need for formulation optimization, the findings support continued development of oxfendazole as a macrofilaricidal drug for onchocerciasis.

Piperaquine tetraphosphate (PQP), a long‐acting antimalarial, is being considered in a combination for chemoprevention. Dihydroartemisinin‐piperaquine tablets (hard and dispersible) approved for the treatment of acute uncomplicated malaria should be administered in a fasted state, as PQP bioavailability increases with food. A new taste‐masked dispersible granules PQP formulation aims to minimize the impact of food on drug exposure. This randomized, open label, parallel group, Phase I pilot study was conducted between 24th July 2023, and 3rd January 2024, at the Ifakara Health Institute, Bagamoyo, Tanzania in 60 healthy African adults (five cohorts of 12). Single‐dose pharmacokinetics and relative systemic exposure of the oral PQP dispersible granules formulation prototype (320 mg) was compared to the hard tablet when fasted and PQP granules in three different fed conditions. In the fasted state, the relative exposure of PQP granules versus the tablet was 73.9% (90% CI 48.3, 113.0) for Cmax and 86.5% (68.2, 109.6) for AUC0‐t. Following a typical East African low‐fat meal, a standard high‐fat meal, or 250 mL whole milk, the relative exposure of PQP granules versus the fasted state was 202% (90% CI 132, 311), 275% (193, 391), and 294% (203, 425) for Cmax and 164% (124, 217), 184% (148, 228), and 195% (147, 259) for AUC0‐t, respectively. Both formulations were well tolerated with one drug‐related adverse event (moderate migraine). No severe or serious adverse events or clinically relevant laboratory or electrocardiograph changes were observed. PQP dispersible granules had lower systemic exposures versus the tablet when fasted, whereas various meals increased drug exposure.

Background: Though 'Maytenus senegalensis' is one of the medicinal plants widely used in traditional medicine to treat infectious and inflammatory diseases in Africa, there is a lack of safety data regarding its use. Therefore, the study aimed to asselss the safety and tolerability of the antimalarial herbal remedy 'M. senegalensis'. Material and Methods: The study design was an open-label, single-arm, dose-escalation. Twelve eligible male healthy Tanzanians aged 18 to 45 years were enrolled in four study dose groups. Volunteers' safety and tolerability post-investigational product administration were monitored on days 0 to 7,14, and 56. Results: There were no deaths or serious adverse events in any of the study groups, nor any adverse events that resulted in premature discontinuation. The significant mean changes observed in WBC ('p' = 0.003), Neutrophils ('p' = 0.02), Lymphocytes ('p' = 0.001), Eosinophils ('p' = 0.009), Alanine aminotransferase ('p' = 0.002), Creatinine ('p' = 0.03) and Total bilirubin ('p' = 0.004) laboratory parameters were not associated with any signs of toxicity or clinical symptoms. Conclusions: 'M. senegalensis' was demonstrated to be safe and tolerable when administered at a dose of 800 mg every eight hours a day for four days. This study design may be adapted to evaluate other herbal remedies.