A Pharmacokinetics Study for Pediatric Participants With Pulmonary Arterial Hypertension

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The purpose of this study to see how much study drug is in the blood after dosing children with pulmonary arterial hypertension (PAH) and to establish the correct dose for further clinical research.

Condition or disease	Intervention/treatment	Phase
Pulmonary Arterial Hypertension	Drug: Tadalafil- Tablet	Phase 1; Phase 2

Detailed Description:

During Period I, tadalafil will be administered orally, once daily, at a low dose for approximately 5 weeks followed by a high dose for approximately 5 weeks. Dose levels are calculated based on body weight cohorts. Heavy weight cohort >=40 kg, middle weight cohort >=25 kg to <40 kg. Light weight cohort<25 kg. Participants who complete Period 1 may continue taking tadalafil in Period 2 for at least 2 years. Starting dose will not exceed the maximum weight range dose established in Period 1 and may be adjusted based on available safety and efficacy information.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	24 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Multiple Ascending Dose Study of Tadalafil to Assess the Pharmacokinetics and Safety in a Pediatric Population With Pulmonary Arterial Hypertension
Study Start Date :	July 2012
Actual Primary Completion Date :	April 2017
Estimated Study Completion Date :	May 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: tadalafil; The dose of tadalafil will be escalated from low to high for each participant based on body weight for 5 weeks at low dose and 5 weeks at high dose.	Drug: Tadalafil- Tablet; Tadalafil tablets: 2.5 mg and 5 mg, 10 mg, 20 mg and 40 mg (two 20 mg) administered orally, once daily in the heavy weight cohort >=40 kg and middle weight cohort >=25 kg to <40 kg Drug: Tadalafil - Oral suspension Tadalafil Oral suspension: 1 mg, 5 mg administered orally, once daily in the light weight cohort <25 kg

Outcome Measures

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Primary Outcome Measures :

1. Pharmacokinetics: Area under the concentration time curve for tadalafil [ Time Frame: Period 1: pre dose up to 24 hours post dose ]
2. Pharmacokinetics: Maximum plasma concentration for tadalafil [ Time Frame: Period 1: pre dose up to 24 hours post dose ]

Secondary Outcome Measures :

1. Change from baseline to endpoint in World Health Organization (WHO) functional class [ Time Frame: Period 1: baseline, 10 weeks ]
2. Change from baseline to endpoint in 6 minute walk distance for participants greater than or equal to 7 years of age [ Time Frame: Period 1: baseline, 10 weeks ]
3. Percent increase from baseline to endpoint in N Terminal-Pro Brain Natriuretic Peptide (NT-Pro-BNP) [ Time Frame: Period 1: baseline and 10 weeks ]
4. Percentage of participants with clinical worsening [ Time Frame: Period 2: baseline up to 2 years ]

Eligibility Criteria

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Ages Eligible for Study:	6 Months to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Currently have a diagnosis of PAH that is either:

  • idiopathic (including hereditary), related to collagen vascular disease, related to anorexigen use, associated with surgical repair, of at least 6 month duration, of a congenital systemic to pulmonary shunt (for example, atrial septal defect, ventricular septal defect, patent ductus arteriosus).
• Have a history of the diagnosis of PAH established by a resting mean pulmonary artery pressure ≥25 mm Hg, pulmonary artery wedge pressure ≤15 mm Hg, and a pulmonary vascular resistance (PVR) ≥3 Wood units via right heart catheterization. In the event that a pulmonary artery wedge pressure is unable to be obtained during right heart catheterization, participants with a left ventricular end diastolic pressure <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 I, II or III at the time of enrollment

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 to 18 mm Hg) aortic or mitral valve disease (that is, 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 as determined by the physician
• History of atrial septostomy or Potts Shunt within 3 months before administration of study drug
• Unrepaired congenital heart disease

Contacts and Locations

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Locations

United States, Colorado
Children's Hospital of Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Children's Heathcare of Atlanta, Inc. at Egleston
Atlanta, Georgia, United States, 30322
United States, Indiana
Riley Hosptial for Children
Indianapolis, Indiana, United States, 46202-5225
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205-2664
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Canada, Quebec
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
Montreal, Quebec, Canada, H3T 1C5
Canada
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
Toronto, Canada, M5G 1X8
France
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Marseille, France, 13385
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Paris, France, 75743
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Toulouse, France, 31026
Poland
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Gdansk, Poland, 80-952
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Warszawa, Poland, 00-576
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Warszawa, Poland, 04-730
Spain
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Barcelona, Spain, 08035
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Madrid, Spain, 28041
United Kingdom
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Bloomsbury, London, United Kingdom, WC1N 3JH

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-5PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Click here for more information about this study: A Pharmacokinetics Study for Pediatric Participants With Pulmonary Arterial Hypertension (PAH) 

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT01484431 History of Changes
Other Study ID Numbers:	12917; H6D-MC-LVIG ( Other Identifier: Eli Lilly and Company )
First Posted:	December 2, 2011
Last Update Posted:	August 21, 2017
Last Verified:	August 2017

Additional relevant MeSH terms:

Hypertension; Familial Primary Pulmonary Hypertension; Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases	Tadalafil; Vasodilator Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Urological Agents