Recruitment

Recruitment Status
Completed
Estimated Enrollment
18

Inclusion Criterias

On a stable regimen of background therapy for at least 3 months prior to starting study drug
Have history of right heart catheterization within two years demonstrating pulmonary arterial hypertension
Body mass index (BMI) ≤34 kg/m^2 and a total body weight >40 kg (>88 lbs)
...
On a stable regimen of background therapy for at least 3 months prior to starting study drug
Have history of right heart catheterization within two years demonstrating pulmonary arterial hypertension
Body mass index (BMI) ≤34 kg/m^2 and a total body weight >40 kg (>88 lbs)
If female, cannot be pregnant or breastfeeding. Females of reproductive potential must agree to agree to use (and/or have their partner use) two (2) acceptable methods of birth control throughout the study and until 2 weeks after the last dose of study drug is administered
Has Group 1 pulmonary hypertension (PAH) as defined by the Dana Point 2008 Clinical Classification including: idiopathic PAH (IPAH), Heritable PAH, Drug and toxin-induced PAH, PAH associated with connective tissue disease or congenital heart disease (repaired simple cardiac defects at least 1 year status post corrective surgery, with no residual intracardiac or extracardiac shunt)
Have hemoglobin >75% of the lower limit of the normal range
Had pulmonary function testing within one year of starting study medication demonstrating total lung capacity (TLC) >70% predicted, forced expiratory volume in 1 second (FEV1) >70% predicted

Exclusion Criterias

Consume excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
Unable to refrain from or anticipates the use of prostanoid therapies beginning approximately 2 weeks before start of study and throughout the study
History of significant multiple and/or severe allergies
...
Consume excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
Unable to refrain from or anticipates the use of prostanoid therapies beginning approximately 2 weeks before start of study and throughout the study
History of significant multiple and/or severe allergies
Major surgery or donated blood within previous 8 weeks
Have secondary forms of pulmonary hypertension due to pulmonary veno-occlusive disease (PVOD), or pulmonary capillary hemangiomatosis (PCH)
Interstitial lung disease
Uncorrected hypokalemia or hypomagnesemia
Unable to refrain from or anticipates the use of organic nitrates (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol) beginning approximately 2 weeks before start of study and throughout the study
Participated in another investigational study within 4 weeks
Regular user of illicit drugs, or has a history of drug (including alcohol) abuse, within approximately 6 months
Taking medications that are potent inhibitors or inducers of Cytochrome P450 3A4 (CYP3A4) including but not limited to cyclosporine, systemic itraconazole or ketoconazole, glyburide, erythromycin, clarithromycin, or telithromycin, nefazodone, protease inhibitors, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifampicin, St John's wort, diltiazem and verapamil) or has discontinued treatment <3 weeks prior to the start of the study. Concomitant medications, including anticoagulants, angiotensin converting enzyme (ACE) -inhibitors, diuretics, bosentan, ambrisentan and selected calcium channel blockers (e.g., amlodipine) may be allowed at the discretion of the investigator with the concurrence of the Sponsor.
Pulmonary hypertension subtypes including the following according to Dana Point 2008 Clinical Classification: human immunodeficiency virus (HIV) infection, portal hypertension, schistosomiasis, chronic hemolytic anemia, persistent pulmonary hypertension of the newborn (PPHN), pulmonary hypertension due to left heart diseases such as systolic dysfunction, diastolic dysfunction or valvular disease, pulmonary hypertension due to lung diseases and/or hypoxia (e.g. chronic obstructive pulmonary disease, interstitial lung disease, other pulmonary diseases with mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, and developmental abnormalities), chronic thromboembolic pulmonary hypertension (CTEPH), hematologic disorder (myeloproliferative disorders, splenectomy), systemic disorders (sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis), metabolic disorders (glycogen storage disease, Gaucher disease, thyroid disorders) or other disorder (tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis)
Resting systolic blood pressure <105 mmHg, or resting heart rate ≥110/min
Family history of Long QT Syndrome
Pregnant or breast-feeding, or expecting to conceive

Summary

Conditions
Pulmonary Arterial Hypertension
Type
Interventional
Phase
Phase 1
Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: Double (Participant, Investigator)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 70 years
Gender
Both males and females

Inclusion Criterias

On a stable regimen of background therapy for at least 3 months prior to starting study drug
Have history of right heart catheterization within two years demonstrating pulmonary arterial hypertension
Body mass index (BMI) ≤34 kg/m^2 and a total body weight >40 kg (>88 lbs)
...
On a stable regimen of background therapy for at least 3 months prior to starting study drug
Have history of right heart catheterization within two years demonstrating pulmonary arterial hypertension
Body mass index (BMI) ≤34 kg/m^2 and a total body weight >40 kg (>88 lbs)
If female, cannot be pregnant or breastfeeding. Females of reproductive potential must agree to agree to use (and/or have their partner use) two (2) acceptable methods of birth control throughout the study and until 2 weeks after the last dose of study drug is administered
Has Group 1 pulmonary hypertension (PAH) as defined by the Dana Point 2008 Clinical Classification including: idiopathic PAH (IPAH), Heritable PAH, Drug and toxin-induced PAH, PAH associated with connective tissue disease or congenital heart disease (repaired simple cardiac defects at least 1 year status post corrective surgery, with no residual intracardiac or extracardiac shunt)
Have hemoglobin >75% of the lower limit of the normal range
Had pulmonary function testing within one year of starting study medication demonstrating total lung capacity (TLC) >70% predicted, forced expiratory volume in 1 second (FEV1) >70% predicted

Exclusion Criterias

Consume excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
Unable to refrain from or anticipates the use of prostanoid therapies beginning approximately 2 weeks before start of study and throughout the study
History of significant multiple and/or severe allergies
...
Consume excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
Unable to refrain from or anticipates the use of prostanoid therapies beginning approximately 2 weeks before start of study and throughout the study
History of significant multiple and/or severe allergies
Major surgery or donated blood within previous 8 weeks
Have secondary forms of pulmonary hypertension due to pulmonary veno-occlusive disease (PVOD), or pulmonary capillary hemangiomatosis (PCH)
Interstitial lung disease
Uncorrected hypokalemia or hypomagnesemia
Unable to refrain from or anticipates the use of organic nitrates (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol) beginning approximately 2 weeks before start of study and throughout the study
Participated in another investigational study within 4 weeks
Regular user of illicit drugs, or has a history of drug (including alcohol) abuse, within approximately 6 months
Taking medications that are potent inhibitors or inducers of Cytochrome P450 3A4 (CYP3A4) including but not limited to cyclosporine, systemic itraconazole or ketoconazole, glyburide, erythromycin, clarithromycin, or telithromycin, nefazodone, protease inhibitors, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifampicin, St John's wort, diltiazem and verapamil) or has discontinued treatment <3 weeks prior to the start of the study. Concomitant medications, including anticoagulants, angiotensin converting enzyme (ACE) -inhibitors, diuretics, bosentan, ambrisentan and selected calcium channel blockers (e.g., amlodipine) may be allowed at the discretion of the investigator with the concurrence of the Sponsor.
Pulmonary hypertension subtypes including the following according to Dana Point 2008 Clinical Classification: human immunodeficiency virus (HIV) infection, portal hypertension, schistosomiasis, chronic hemolytic anemia, persistent pulmonary hypertension of the newborn (PPHN), pulmonary hypertension due to left heart diseases such as systolic dysfunction, diastolic dysfunction or valvular disease, pulmonary hypertension due to lung diseases and/or hypoxia (e.g. chronic obstructive pulmonary disease, interstitial lung disease, other pulmonary diseases with mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, and developmental abnormalities), chronic thromboembolic pulmonary hypertension (CTEPH), hematologic disorder (myeloproliferative disorders, splenectomy), systemic disorders (sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis), metabolic disorders (glycogen storage disease, Gaucher disease, thyroid disorders) or other disorder (tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis)
Resting systolic blood pressure <105 mmHg, or resting heart rate ≥110/min
Family history of Long QT Syndrome
Pregnant or breast-feeding, or expecting to conceive

Tracking Information

NCT #
NCT01926509
Collaborators
Not Provided
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.