A Study of Tadalafil in Pediatric Participants With Pulmonary Arterial Hypertension (PAH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01824290
First received: April 1, 2013
Last updated: September 19, 2014
Last verified: September 2014
  Purpose

The main purpose of this study is to evaluate the safety and efficacy of tadalafil in pediatric participants with pulmonary arterial hypertension. Participants will receive study treatment for 6 months in the double-blind period (Period 1), and then will be eligible to enroll into an open-label 2 year extension period (Period 2) during which participants will receive tadalafil.


Condition Intervention Phase
Hypertension, Pulmonary
Drug: Tadalafil
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind Efficacy and Safety Study of the Phosphodiesterase Type 5 Inhibitor Tadalafil in Pediatric Patients With Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Period 1: Change from Baseline to Week 24 in a 6 Minute Walk (MW) Distance in Meters [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Period 1: Time to First Occurence of Clinical Worsening (CW) [ Time Frame: Baseline through Week 24 ] [ Designated as safety issue: No ]
  • Period 2: Time to First Occurence of CW [ Time Frame: Baseline through Study Completion (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Period 2: Percentage of Participants Who Experience CW [ Time Frame: Baseline through Study Completion (Estimated up to 24 Months) ] [ Designated as safety issue: No ]
  • Period 1: Percentage of Participants Who Experience CW [ Time Frame: Baseline through Week 24 ] [ Designated as safety issue: No ]
  • Period 1: Pharmacokinetics (PK): Apparent Clearance (CL/F) of tadalafil [ Time Frame: Week 2, 4, 16 and 24 ] [ Designated as safety issue: No ]

Estimated Enrollment: 134
Study Start Date: February 2014
Estimated Study Completion Date: December 2022
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tadalafil

Period 1 (6-month double-blind): Final tadalafil doses will be assigned after the weight cohort completion from H6D-MC-LVIG (NCT01484431). Tadalafil doses may range from 5 milligram (mg) to 40 mg depending on body weight cohorts. Heavy weight cohort ≥40 kilogram (kg), Middle weight cohort ≥25 kg to <40 kg: administered orally by tablets once a day. Light weight cohort <25 kg: administered orally by suspension once a day.

Period 2 (2-year open-label extension): Participants receiving tadalafil in Period 1 will continue at same dose in Period 2.

Drug: Tadalafil
Administered orally by tablet form for heavy and middle weight participants. Administered orally by suspension for light weight participants.
Other Names:
  • LY450190
  • Cialis
  • Adcirca
  • IC351
Placebo Comparator: Placebo

Period 1 (6-month double-blind): Final placebo dose will be assigned after the weight cohort completion from H6D-MC-LVIG (NCT01484431) to maintain blinding depending on body weight cohort.

Period 2 (2-year open-label extension): Participants receiving placebo in Period 1 will receive tadalafil in Period 2 at the corresponding tadalafil dose in that participant's weight group.

Drug: Placebo
Administered orally by tablet for heavy and middle weight participants. Administered orally by suspension for light weight participants.

  Eligibility

Ages Eligible for Study:   6 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥6 months to <18 years of age at screening
  • Currently have a diagnosis of PAH that is either:

    • idiopathic, including hereditary
    • related to connective tissue disease
    • related to anorexigen use
    • associated with surgical repair of at least 6-month duration of congenital systemic to pulmonary shunt (eg, atrial septal defect, ventricular septal defect, patent ductus arteriosus)
  • Have a history of a diagnosis of PAH established by a resting mean pulmonary artery pressure (mPAP) ≥25 millimeter of mercury (mm Hg), pulmonary artery wedge pressure ≤15 mm Hg, and a pulmonary vascular resistance (PVR) ≥3 Wood units via right heart catheterization (RHC). In the event that a pulmonary artery wedge pressure cannot be obtained during RHC, participants with a left ventricular end diastolic pressure (LVEDP) <15 mm Hg, with normal left heart function, and absence of mitral stenosis on echocardiography can be eligible for enrollment
  • Have a World Health Organization (WHO) functional class value of II or III at the time of screening
  • All participants must be receiving an endothelin receptor antagonist (ERA) (such as bosentan or ambrisentan) and must be on a maintenance dose with no change in dose (other than weight-based adjustments) for at least 12 weeks prior to screening and have a screening aspartate transaminase (AST)/alanine transaminase (ALT) <3 times the upper limit of normal (ULN)
  • If on conventional PAH medication, including but not restricted to, anticoagulants, diuretics, digoxin, and oxygen therapy, the participant must be on stable doses with no changes (other than weight-based adjustments) for at least 4 weeks before screening
  • Female participants of childbearing potential must test negative for pregnancy during screening. Furthermore, female participants must agree to abstain from sexual activity or to use two different reliable methods of birth control as determined by the Investigator during the study. Examples of reliable birth control methods include true abstinence as a lifestyle choice (periodic sexual abstinence method is not acceptable); the use of oral contraceptives; a reliable barrier method of birth control (diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices)
  • Written informed consent from parents (and written assent from appropriately aged participants) will be obtained prior to any study procedure being performed

Exclusion Criteria:

  • Have pulmonary hypertension related to conditions other than specified above, including but not limited to chronic thromboembolic disease, portal pulmonary hypertension, left-sided heart disease or lung disease and hypoxia
  • History of left-sided heart disease, including any of the following:

    • clinically significant [pulmonary artery occlusion pressure (PAOP) 15-18 mm Hg] aortic or mitral valve disease (ie, aortic stenosis, aortic insufficiency, mitral stenosis, moderate or greater mitral regurgitation)
    • pericardial constriction
    • restrictive or congestive cardiomyopathy
    • left ventricular ejection fraction <40% by multigated radionucleotide angiogram (MUGA), angiography, or echocardiography
    • left ventricular shortening fraction <22% by echocardiography
    • life-threatening cardiac arrhythmias
    • symptomatic coronary artery disease within 5 years of study entry
  • Unrepaired congenital heart disease
  • Have a history of angina pectoris or other condition that was treated with long- or short-acting nitrates within 12 weeks before administration of study drug
  • Have severe hepatic impairment, Child-Pugh Grade C
  • Have severe renal insufficiency, defined as receiving renal dialysis or having a measured or estimated creatinine clearance (CC) <30 millimeter per minute (mL/min) (Schwartz Formula)
  • Diagnosed with a retinal disorder (eg, hereditary retinal disorders, retinopathy of the preterm participant and other retinal disorders)
  • Have severe hypotension or uncontrolled hypertension as determined by the Investigator
  • Have significant parenchymal lung disease
  • Have bronchopulmonary dysplasia
  • Concurrent phosphodiesterase type 5 (PDE5) inhibitor therapy (sildenafil or vardenafil) or has received PDE5 inhibitor therapy within 12 weeks prior to the first study drug dosing
  • Concurrent therapy with prostacyclin or its analogues within 12 weeks of screening
  • Commenced or discontinued a chronic conventional PAH medication including but not restricted to: diuretics, anti-coagulants, digoxin, and oxygen therapy within 4 weeks of screening
  • Currently receiving treatment with doxazosin, nitrates, or cancer therapy
  • Current treatment with potent Cytochrome P450 3A4 (CYP3A4) inhibitors, such as antiretroviral therapy (protease inhibitor), systemic ketoconazole, or systemic itraconazole, or chronic use of potent CYP3A4 inducers, such as rifampicin
  • Are nursing or pregnant
  • Have previously completed or withdrawn from this study (LVHV), or any other study investigating tadalafil
  • Have received tadalafil therapy within 12 weeks prior to the first study drug dosing or are hypersensitive to tadalafil
  • Have allergy to the excipients, notably lactose
  • Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study by the Sponsor
  • Unable to take orally administered tablets (without chewing, crushing or breaking) or suspension
  • Are Investigator site personnel directly affiliated with this study or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted
  • Diagnosis of Down syndrome
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01824290

Contacts
Contact: There may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) 1-317-615-4559

  Show 50 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01824290     History of Changes
Other Study ID Numbers: 10609, H6D-MC-LVHV, 2012-002354-23
Study First Received: April 1, 2013
Last Updated: September 19, 2014
Health Authority: United States: Food and Drug Administration
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: The Italian Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
Turkey: Ministry of Health

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Tadalafil
Phosphodiesterase 5 Inhibitors
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on October 01, 2014