ABSTRACT
Objectives@#Vitex negundo is an endemic shrub in the Philippines which has been clinically tested for the symptomatic treatment of cough in syrup and tablet formats. However, the effectiveness and safety of the capsule have not been formally documented in a clinical trial setting. Therefore, in compliance with the Philippine FDA directive, this study compared the efficacy and safety of the capsule and tablet formats after three days of treatment among Filipinos with acute uncomplicated cough. @*Methods@#This is a Phase 3b randomized, open-label, parallel-group non-inferiority study with 335 subjects using improvement based on Global Rating of Change Scale scores as primary efficacy endpoint and several secondary endpoints. Descriptive and inferential analyses were performed. The Farrington-Manning Method of Z-test with -10% non-inferiority margin was used for the primary outcome. Appropriate inferential tests were used for the secondary outcomes. @*Results@#Of 335 enrolled subjects, 170 were randomized to the capsule group and 165 to the tablet group with comparable baseline characteristics. The proportion of success based on the Global Rating of Change Scale rated by patients was 95.71% and 91.19% for the capsule and tablet groups, respectively. Based on doctors’ ratings, they were 96.93% and 94.34%, respectively. In addition, the Farrington-Manning Method of Z-test revealed the capsule was not inferior to the tablet based on patients’ and doctors’ ratings (90% Confidence Intervals: -0.0086 to 0.0988 and -0.0228 to 0.0747, respectively). The intention-to-treat analysis also showed non-inferiority, indicating robust results. Significant and similar improvements in cough severity and quality of life were observed in both groups based on Cough Severity Diary scores and Leicester Cough Questionnaire for acute cough, respectively. There were also improvements in the Forced Expiratory Volume at 1 second [FEV1] (capsule group) and Peak Expiratory Flow Rate [PEFR] (both groups), but these were not clinically significant. The safety profiles were also comparable (p= 0.4437) with 1.23% and 2.52% incidence of adverse events, respectively, all of which were mild and assessed as not related to the drug. @*Conclusion@#In terms of efficacy, Ascof® Forte capsule was non-inferior to Ascof® Forte tablet in treating acute uncomplicated cough among Filipinos based on Global Rating of Change Scale scores as rated by patients and doctors. Both treatments showed significant and similar improvements in cough severity and quality of life. They were also comparable in safety with few adverse events in both groups, all mild and assessed unrelated to drug intake.
Subject(s)
CapsulesABSTRACT
@#<p style="text-align: justify;"><strong>Objective.</strong> Proof of bioequivalence is important for the interchangeability of pharmaceutically equivalent drug products. This study aimed to compare the rate and extent of absorption of meloxicam 15 mg tablet of Pascual Laboratories, Inc. (Test) with meloxicam 15 mg tablet (Mobic) of Boehringer Ingelheim (Reference) in healthy Filipino men. In addition, the study also determined the safety and tolerability of single doses of the said medications, under the same conditions.</p><p style="text-align: justify;"><strong>Methods.</strong> This was a randomized, open label, blind-endpoint analysis, truncated, crossover study with single drug doses administered in the fasting condition in each of the two treatment periods, separated by a two-week washout period. Pharmacokinetic blood sampling was performed up to 72 h post-dose. Plasma samples were analyzed using a validated liquid chromatography with tandem mass spectrometry technology. The primary endpoints were: area under plasma-concentration-time curve from time zero to the last observed concentration at time 72 h (AUC0-72) and maximum plasma concentration (Cmax) for meloxicam.</p><p style="text-align: justify;"><strong>Results.</strong> Eighteen men (mean age 21.5 years; mean body mass index 22.9 kg/m2) completed the study. When administered one meloxicam 15 mg tablet, the ratios of the geometric means of the primary endpoints AUC0-72 and Cmax, were within the established bioequivalence limits of 80% to 125% compared with Mobic 15 mg tablet: 104.07% (90% Confidence Interval [CI]: 100.26, 108.03), and 103.34% (90% CI: 96.22, 110.97), respectively. No adverse event was reported.</p><p style="text-align: justify;"><strong>Conclusion.</strong> Meloxicam 15 mg tablet of Pascual Laboratories, Inc. and the innovator Mobic 15 mg tablet are bioequivalent. Single doses of both products were safe and well tolerated.</p>