Safety evaluation of Mikania glomerata and Mikania laevigata in healthy volunteers: A randomized, open label and multiple dose phase I clinical trial

Ethnopharmacological relevance: Mikania glomerata (MG) and Mikania laevigata (ML) leaves are used inter-changeably in Brazilian ethno-medicine, mainly for the treatment of respiratory diseases, but there is no clinical trial for the safety evaluation of these species at different doses.Aim of the study: To evaluate the safety of two oral solutions from each species, across two weeks of use and two doses.Materials and methods: A randomized, open-label, multiple dose, two-arm trial. Participants (n = 19) were randomly allocated to one of the arms of the trial. Group 1 received 15 mL of MG oral solution twice daily for 7 days and then 30 mL twice daily for 7 days. Group 2 received ML oral solution in the same manner. After 14 days, the participants went through a washout period of 7 days before cross-over to the other group. Adverse events (AEs), clinical parameters and blood markers were monitored at the beginning (T0) and at the end of each week of the study, which was concluded after six weeks. AEs were classified as mild, moderate or severe, and according to their correlation with the medicine intake, the measured parameters were compared to T0 by generalized estimating equations (GEE) to determine those affected by the use of the oral solutions (p < 0.05).Results: MG was not correlated to any of the reported AEs; its use affected three of the evaluated parameters: total protein, diastolic blood pressure and urea, although all the changes were within the normal range for healthy individuals. ML was correlated to one moderate AE of pyrosis and the alteration of 12 parameters: erythrocytes, hemoglobin, hematocrit, monocytes, time of prothrombin, time of thromboplastin, albumin, alkaline phospha-tase, total protein, urea, potassium and sodium. All changes were within the normal range for healthy individuals.Conclusion: ML and MG are considered safe for humans under the dose regimen tested.