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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Treatment A (adult formulation); Drug: Treatment B (pediatric formulation)

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czech Republic
  • Pilsen, Czech Republic, 323 00
    • CEPHA s.r.o.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence AB; Subjects receive treatment A in Period 1 followed by treatment B in Period 2 with a washout phase of 10 to 14 days between the two treatment periods	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.; Other Names: Opsumit; Drug: 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.
Experimental: Sequence BA; Subjects receive treatment B in Period 1 followed by treatment A in Period 2 with a washout phase of 10 to 14 days between the two treatment periods	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.; Other Names: Opsumit; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Number of adverse events and serious adverse events, including abnormal laboratory findings	from baseline to Day 10-13 post-dose
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

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Patricia Sidharta, PharmD, PhD, Actelion

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 11, 2015
• First Submitted That Met QC Criteria: June 17, 2015
• First Posted (Estimate): June 22, 2015

Study Record Updates

• Last Update Posted (Estimate): April 22, 2016
• Last Update Submitted That Met QC Criteria: April 21, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: safety; macitentan; biocomparison
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Endothelin Receptor Antagonists; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Macitentan
• Other Study ID Numbers: AC-055-121; 2015-001623-23 (EudraCT Number)