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Bioequivalence of macitentan and tadalafil given as fixed‐dose combination or single‐component tablets in healthy subjects
- Source :
- British Journal of Clinical Pharmacology
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- 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.
- Subjects :
- Adult
Male
macitentan
Adolescent
Fixed-dose combination
Bioequivalence
Pharmacology
030226 pharmacology & pharmacy
Tadalafil
Young Adult
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Pharmacokinetics
pulmonary arterial hypertension
medicine
Humans
Hypoglycemic Agents
Pharmacology (medical)
030212 general & internal medicine
Adverse effect
Active metabolite
Macitentan
bioequivalence
Sulfonamides
Cross-Over Studies
business.industry
Healthy subjects
Original Articles
Middle Aged
Healthy Volunteers
Metformin
fixed‐dose combination
Drug Combinations
Pyrimidines
Therapeutic Equivalency
chemistry
Area Under Curve
Delayed-Action Preparations
Original Article
Female
business
Tablets
medicine.drug
Subjects
Details
- ISSN :
- 13652125 and 03065251
- Volume :
- 86
- Database :
- OpenAIRE
- Journal :
- British Journal of Clinical Pharmacology
- Accession number :
- edsair.doi.dedup.....32de39e54ed0a875d03df166760e14c2