A Study of Fixed Dose Combination of Macitentan/Tadalafil (10 mg/20 mg) Compared to the Reference Free Combination of Macitentan and Tadalafil in Healthy Adult Participants

Actelion Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Tadalafil 20 mg; Drug: Macitentan 10 mg; Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Study type: Interventional

Funder types: Industry

Identifiers

NCT05236231

CR109140

67896062PAH1002 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to demonstrate bioequivalence on the primary pharmacokinetic (PK) parameters between macitentan and tadalafil administered as a fixed dose combination (FDC) (test) of macitentan/tadalafil and the co- administered free combination (reference) of macitentan (Opsumit) and tadalafil (Adcirca) in fasted conditions in healthy adult participants; and to evaluate the effect of food on the primary PK parameters of macitentan and tadalafil administered as an FDC of macitentan/tadalafil in fed versus fasted conditions in healthy adult participants.

Enrollment: 40 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy on the basis of physical examination and medical history, performed at screening. If there are any abnormalities, they must be considered not clinically relevant and this determination must be recorded in the participant's source documents and initialed by the investigator
• Systolic blood pressure (SBP) between 100 and 145 millimeters of mercury (mm Hg) (inclusive), diastolic blood pressure (DBP) between 50 and 90 mm Hg (inclusive), and pulse rate between 45 and 90 beats per minute (inclusive) at screening, supine for at least 5 minutes and after 3 minutes of standing
• Twelve-lead electrocardiogram (ECG) without clinically relevant abnormalities, at the discretion of the investigator, measured after the participant is supine for at least 5 minutes, at screening
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 30 days after the last study intervention intake
• Willing and able to adhere to the lifestyle restrictions specified in this protocol

Exclusion criteria

• Known allergies, hypersensitivity, or intolerance to macitentan, tadalafil, or drug of the same class, or its excipients
• History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the study intervention(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed)
• Veins unsuitable for intravenous puncture on either arm (example, veins that are difficult to locate, access, or puncture, and veins with a tendency to rupture during or after puncture)
• Known hereditary degenerative retinal disorders, including retinitis pigmentosa

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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40 participants in 6 patient groups

Treatment Sequence ABC

Experimental group

Description:

Participants will receive single oral dose of fixed dose combination (FDC) of macitentan/tadalafil under fasting conditions in (test) (Treatment A) Treatment Period 1 followed by single oral dose of FDC of macitentan/tadalafil under fed conditions (test) (Treatment B) in Treatment Period 2 and then single oral dose of macitentan/tadalafil under fasting conditions (reference) (Treatment C) in Treatment Period 3 on Day 1 of each Treatment Period. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Treatment:

Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Drug: Macitentan 10 mg

Drug: Tadalafil 20 mg

Treatment Sequence BCA

Experimental group

Description:

Participants will receive Treatment B in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Treatment:

Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Drug: Macitentan 10 mg

Drug: Tadalafil 20 mg

Treatment Sequence CAB

Experimental group

Description:

Participants will receive Treatment C in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Treatment:

Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Drug: Macitentan 10 mg

Drug: Tadalafil 20 mg

Treatment Sequence ACB

Experimental group

Description:

Participants will receive Treatment A in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Treatment:

Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Drug: Macitentan 10 mg

Drug: Tadalafil 20 mg

Treatment Sequence CBA

Experimental group

Description:

Participants will receive Treatment C in Treatment Period 1 followed by Treatment B in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Treatment:

Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Drug: Macitentan 10 mg

Drug: Tadalafil 20 mg

Treatment Sequence BAC

Experimental group

Description:

Participants will receive Treatment B in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment C in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Treatment:

Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Drug: Macitentan 10 mg

Drug: Tadalafil 20 mg