A Pharmacokinetics Study for Pediatric Participants With Pulmonary Arterial Hypertension

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01484431
First received: November 30, 2011
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Pulmonary Arterial Hypertension
Drug: Tadalafil- Tablet
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Pharmacokinetics: Area under the concentration time curve for tadalafil [ Time Frame: Period 1: pre dose up to 24 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum plasma concentration for tadalafil [ Time Frame: Period 1: pre dose up to 24 hours post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline to endpoint in World Health Organization (WHO) functional class [ Time Frame: Period 1: baseline, 10 weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Percent increase from baseline to endpoint in N Terminal-Pro Brain Natriuretic Peptide (NT-Pro-BNP) [ Time Frame: Period 1: baseline and 10 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of participants with clinical worsening [ Time Frame: Period 2: baseline up to 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: July 2012
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


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.

  Eligibility

Ages Eligible for Study:   6 Months to 17 Years
Genders Eligible for Study:   Both
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
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: NCT01484431

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

Locations
United States, Colorado
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. Recruiting
Denver, Colorado, United States, 80218
Contact: Eli Lilly         
United States, Georgia
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. Recruiting
Atlanta, Georgia, United States, 30322
Contact: Eli Lilly         
United States, Ohio
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. Recruiting
Columbus, Ohio, United States, 43205
Contact: Eli Lilly         
United States, Pennsylvania
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. Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Eli Lilly         
United States, Tennessee
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. Recruiting
Memphis, Tennessee, United States, 38103
Contact: Eli Lilly         
United States, Texas
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. Recruiting
Houston, Texas, United States, 77030
Contact: Eli Lilly         
United States, Utah
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. Recruiting
Salt Lake City, Utah, United States, 84102
Contact: Eli Lilly         
Canada, Ontario
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. Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Eli Lilly         
Canada, Quebec
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. Recruiting
Montreal, Quebec, Canada, H3T 1C5
Contact: Eli Lilly         
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. Recruiting
Marseille, France, 13385
Contact: Eli Lilly         
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. Not yet recruiting
Paris, France, 75743
Contact: Eli Lilly         
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. Recruiting
Toulouse, France, 31026
Contact: Eli Lilly         
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. Recruiting
Gdansk, Poland, 80-952
Contact: Eli Lilly         
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. Recruiting
Warsaw, Poland, 04-730
Contact: Eli Lilly         
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. Recruiting
Barcelona, Spain, 08035
Contact: Eli Lilly         
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. Recruiting
Madrid, Spain, 28041
Contact: Eli Lilly         
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. Recruiting
Bloomsbury, London, United Kingdom, WC1N 3JH
Contact: Eli Lilly         
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

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01484431     History of Changes
Other Study ID Numbers: 12917, H6D-MC-LVIG
Study First Received: November 30, 2011
Last Updated: June 2, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Research Ethics Committee
Spain: Ethics Committee
Poland: Ethics Committee
France: Institutional Ethical Committee
Canada: Ethics Review Committee

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

ClinicalTrials.gov processed this record on July 29, 2014