A Study of Macitentan/Tadalafil Combination Administered... | NCT04540744

ID	Type	Description	Link
2020-000566-42	EudraCT Number
67896062PAH1001	Other Identifier	Janssen Research & Development, LLC

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment Sequence AB	Experimental	Participants will receive a single oral dose of fixed dose combination (FDC) of macitentan/tadalafil (10 milligram [mg]/20 mg) in fasted conditions (test) (Treatment A) in treatment period 1 followed by a single oral dose of a free combination of 10 mg macitentan and 20 mg tadalafil in fasted conditions (reference) (Treatment B) in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days.	Drug: FDC of macitentan/tadalafil (10 mg/20 mg) Drug: Macitentan 10 mg Drug: Tadalafil 20 mg
Treatment Sequence BA	Experimental	Participants will receive Treatment B in treatment period 1 followed by Treatment A in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days.	Drug: FDC of macitentan/tadalafil (10 mg/20 mg) Drug: Macitentan 10 mg Drug: Tadalafil 20 mg

Interventions

Name	Type	Description	Arm Group Labels	Other Names
FDC of macitentan/tadalafil (10 mg/20 mg)	Drug	FDC of macitentan/tadalafil (10 mg/20 mg) tablet will be administered orally as per assigned treatment sequence.	Treatment Sequence AB

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan, its Metabolite ACT-132577, and Tadalafil	Cmax is defined as maximum observed plasma analyte concentration.	Predose and up to 216 hours post dose (Up to Day 10)
Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUC [0-last]) of Macitentan, its Metabolite ACT-132577, and Tadalafil	AUC(0-last) is the area under the plasma analyte concentration-time curve from time zero to time of the last quantifiable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.	Predose and up to 216 hours post dose (Up to Day 10)
Area Under the Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of Macitentan, its Metabolite ACT-132577, and Tadalafil	AUC (0-infinity) is the area under the analyte concentration-time curve (AUC) from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable (non-BQL) analyte concentration; and lambda(z) is apparent terminal elimination rate constant.	Predose and up to 216 hours post dose (Up to Day 10)

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 8 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Must sign an informed consent form (ICF) indicating they understand the purpose of, and procedures required for, the study and are willing to participate in the study, before starting any screening activities
Body mass index (BMI; weight [kg]/height^2 [m]^2) between 18.5 and 30.0 kilogram per meter square (kg/m^2) inclusive, and body weight not less than 50.0 kg at screening
Healthy on the basis of physical examination, medical and surgical history, performed at screening. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
Systolic blood pressure (SBP) between 100 and 145 millimeter of Mercury (mmHg) (inclusive) and diastolic blood pressure (DBP) between 50 and 90 mmHg (inclusive) at screening, preferably measured on the right arm, supine after 5 minutes of rest and standing after 3 minutes
Twelve-lead electrocardiogram (ECG) with heart rate between 45 and 90 beats per minute (bpm) and without clinically relevant abnormalities, at the discretion of the investigator, measured after the participant is supine for at least 5 minutes, at screening
During the study (from the day of first study drug intake onwards) and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after the last study drug intake, a male participant must agree: (a) to wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male participant should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak); (b) not to donate sperm for the purpose of reproduction.

Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies

Exclusion Criteria:

Female participant who is breastfeeding at screening and/or plans to breastfeed throughout the study until 30 days after last study drug intake
Known allergies, hypersensitivity, or intolerance to any active substance or drugs of the same class, or any excipient of the drug formulation(s)
Values of hepatic aminotransferase (alanine aminotransferase and/or aspartate aminotransferase) greater than (>)1.5 * upper limit of normal at screening
Any loss of vision (permanent or transient blindness in 1 or both eyes, including ophthalmic migraine, transient ischemic attack, retinal artery/vein thrombosis)
Known hereditary degenerative retinal disorders, including retinitis pigmentosa

Name	Affiliation	Role
Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Pharmacology Unit		Merksem		2170	Belgium

IPD Sharing Statement Module

ID	Term
D002243	Carbolines
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D026121	Indole Alkaloids
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006575	Heterocyclic Compounds, 3-Ring