Comparison of the Pharmacokinetic Properties of Two Tablet Formulations of Macitentan in Healthy Adults

Healthy Subjects Clinical Trial

Official title:

Single-center, Open-label, Randomized, Two-treatment, Single-dose, Crossover Study in Healthy Subjects to Investigate the Biocomparison of the Adult and Pediatric Formulation of Macitentan

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02476864
• Other study ID #: AC-055-121
• Secondary ID: 2015-001623-23
• Status: Completed
• Phase: Phase 1
• First received: June 11, 2015
• Last updated: January 7, 2016
• Start date: August 2015
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: State Institute for Drug Control
• Study type: Interventional

Clinical Trial Summary

A study conducted in healthy adults to investigate if a new macitentan tablet leads to the same fate of macitentan in the body (time of onset, time of presence, amount in the blood) as the marketed macitentan tablet.

Description:

The purpose of this study is to establish biocomparison of 2 types of tablets containing macitentan: a pediatric dispersible tablet and the adult film-coated tablet. A single oral dose of each tablet will be given to healthy subjects on 2 different periods separated by a washout phase of 10 to 14 days.

Biocomparison will be based on the comparison of the pharmacokinetic parameters of macitentan with the two types of tablets using specific statistical methods. The pharmacokinetic parameters will be considered equivalent if specific criteria defined in the study protocol are met.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Signed informed consent

• Healthy on the basis of the physical examination, vital signs (systolic and diastolic blood pressure, heart rate), 12-lead ECG, and laboratory tests performed at screening

Exclusion Criteria:

• History or clinical evidence of any disease and/or condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drug

• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions

• History or clinical evidence of alcoholism or drug abuse within the 3 -year period prior to screening

• Excessive caffeine consumption

• Smoking within 3 months prior to screening and inability to refrain from smoking during the course of the study

• Previous treatment with any prescribed medications (including vaccines) or over-the counter medications within 2 weeks prior to first study drug administration

• Loss of 250 mL or more of blood within 3 months prior to screening

• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Treatment A (adult formulation)
Single oral administration of one film-coated tablet containing 10 mg of macitentan as active substance and lactose, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate type A, polysorbate as inactive ingredients.The film coat contains titanium dioxide, talc, xanthan gum, polyvinyl alcohol, and soy lecithin.
• Treatment B (pediatric formulation)
Single oral administration of two dispersible tablets, each containing 5 mg of macitentan as active ingredient and Mannitol delta polymorphic crystals, mannitol, isomalt, isomalt agglomerated, croscarmellose sodium, and magnesium stearate as inactive ingredients.

Locations

Country	Name	City	State
Czech Republic	CEPHA s.r.o.	Pilsen

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

Czech Republic, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of adverse events	Number of adverse events and serious adverse events, including abnormal laboratory findings	from baseline to Day 10-13 post-dose	Yes
Other	ECG abnormalities	ECG evaluation will be based on the cardiac rhythms measured using a standard 12-lead ECG device	from baseline to to Day 10-13 post-dose	Yes
Primary	Plasma pharmacokinetic profile	Pharmacokinetic profile will be determined by the following parameters: Cmax (Maximum plasma concentration), tmax (Time to reach Cmax), t1/2 (Terminal half-life), AUC(0-t) (Area under the plasma concentration-time curve from zero to time t of the last measured concentration above the limit of quantification), AUC(0-inf) (Area under the plasma concentration-time curve from zero to infinity)	From pre-dose to 216 hours post-dose	No