AIMS: To demonstrate the bioequivalence of macitentan/tadalafil fixed-dose combination (FDC) tablets with single-component tablets of macitentan and tadalafil in healthy subjects. METHODS: Studies AC-077-101 and AC-077-103 were single-centre, open-label, single-dose, 2-period, randomized, crossover Phase 1 studies conducted in healthy subjects. Two FDCs were investigated: FDC-1 and FDC-2 in Study AC-077-101 and FDC-2 in Study AC-077-103. Both FDCs contained 10 mg/40 mg of macitentan/tadalafil and differed in excipients and coating materials used. In both studies, pharmacokinetic sampling over 216 hours was conducted, and pharmacokinetic parameters were derived using noncompartmental methods. RESULTS: Bioequivalence of macitentan, its active metabolite ACT-132577, and tadalafil was established for FDC-2 in both studies AC-077-101 and AC-077-103 in which tadalafil as a single component was sourced from the USA and EU, respectively, to fulfil regional regulatory requirements. The area under the plasma concentration-time curve and maximum plasma concentration with 90% confidence intervals of all components were entirely within the bioequivalence limits (0.8000-1.2500). No subject died and no serious adverse events were reported in either studies. CONCLUSION: The FDC-2 tablet containing 10 mg/40 mg of macitentan/tadalafil was bioequivalent to the free combination of 10 mg macitentan and 40 mg tadalafil (both US and EU sourced). Macitentan and tadalafil were well tolerated when administered as FDC or as a free combination.
- Klíčová slova
- bioequivalence, fixed-dose combination, macitentan, pulmonary arterial hypertension, tadalafil,
- MeSH
- dospělí MeSH
- fixní kombinace léků MeSH
- hypoglykemika * farmakologie MeSH
- klinické křížové studie MeSH
- léky s prodlouženým účinkem MeSH
- lidé středního věku MeSH
- lidé MeSH
- metformin * MeSH
- mladiství MeSH
- mladý dospělý MeSH
- plocha pod křivkou MeSH
- pyrimidiny * farmakologie MeSH
- sulfonamidy * farmakologie MeSH
- tablety MeSH
- tadalafil * farmakologie MeSH
- terapeutická ekvivalence MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fixní kombinace léků MeSH
- hypoglykemika * MeSH
- léky s prodlouženým účinkem MeSH
- macitentan MeSH Prohlížeč
- metformin * MeSH
- pyrimidiny * MeSH
- sulfonamidy * MeSH
- tablety MeSH
- tadalafil * MeSH
