NCT01484431

Brief Summary

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

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jul 2012

Longer than P75 for phase_1

Geographic Reach
6 countries

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 30, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 2, 2011

Completed
8 months until next milestone

Study Start

First participant enrolled

July 17, 2012

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 21, 2017

Completed
1.8 years until next milestone

Results Posted

Study results publicly available

February 5, 2019

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 3, 2019

Completed
Last Updated

October 9, 2019

Status Verified

April 1, 2019

Enrollment Period

4.8 years

First QC Date

November 30, 2011

Results QC Date

September 17, 2018

Last Update Submit

September 27, 2019

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (2)

  • Population Pharmacokinetics: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau) for Tadalafil

    Population Pharmacokinetics: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau) for Tadalafil. The measure of dispersion reported is 90% Prediction Intervals and not Confidence Intervals.

    Period 1: Pre Dose and 2, 4, 8, 12, and 24 Hours Post Dose on Days 1, 14 and 49; with single dose measures on Day 1 and steady-state measurements on Days 14 and 49

  • Population Pharmacokinetics: Average Concentration (Cmean,ss) of for Tadalafil at Steady-State.

    Population Pharmacokinetics: Average Concentration (Cmean,ss) of for tadalafil at steady-state. The measure of dispersion reported is 90% Prediction Intervals and not Confidence Intervals.

    Period 1: Pre Dose and 2, 4, 8, 12, and 24 Hours Post Dose on Days 1, 14 and 49; with single dose measures on Day 1 and steady-state measurements on Days 14 and 49

Secondary Outcomes (2)

  • Percentage of Participants With Clinical Worsening

    Baseline Up to 27 Months

  • Number of Participants With Palatability of the Tadalafil Suspension

    Day 35 (high dose)

Study Arms (1)

Tadalafil

EXPERIMENTAL

Light Weight \<25 kg Period 1: 2 milligram (mg) or 4 mg tadalafil administered once daily (QD) in oral suspension formulation for 5 weeks then 8 mg,10 mg,15 mg or 20 mg tadalafil was administered QD in oral suspension formulation for 5 weeks. Middle Weight: 25 kg to \<40 kg Period 1: 5 mg tadalafil tablet administered QD for 5 weeks then 10 mg, 15 mg or 20 mg tablet tadalafil administered QD for 5 weeks. Heavy: ≥40 kg Period 1: 10 mg tadalafil tablet administered QD for 5 weeks then 20 mg or 40 mg tablet tadalafil administered QD for 5 weeks.

Drug: Tadalafil- Tablet or Oral suspension

Interventions

Tadalafil- Tablet or Oral suspensionDRUG

Tadalafil Tablets administered orally. Tadalafil Oral suspension: An aqueous, ready-to-use suspension for oral administration.

Also known as: LY450190
Tadalafil

Eligibility Criteria

Age6 Months - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Children's Heathcare of Atlanta, Inc. at Egleston

Atlanta, Georgia, 30322, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202-5225, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205-2664, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

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, H3T 1C5, Canada

Location

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, M5G 1X8, Canada

Location

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, 13385, France

Location

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, 75743, France

Location

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, 31026, France

Location

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, 80-952, Poland

Location

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.

Warsaw, 00-576, Poland

Location

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.

Warsaw, 04-730, Poland

Location

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, 08035, Spain

Location

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, 28041, Spain

Location

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, WC1N 3JH, United Kingdom

Location

Related Publications (1)

  • Ferguson-Sells L, Velez de Mendizabal N, Li B, Small D. Population Pharmacokinetics of Tadalafil in Pediatric Patients with Pulmonary Arterial Hypertension: A Combined Adult/Pediatric Model. Clin Pharmacokinet. 2022 Feb;61(2):249-262. doi: 10.1007/s40262-021-01052-8. Epub 2021 Aug 11.

    PMID: 34379314DERIVED

Related Links

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

TadalafilSuspensions

Condition Hierarchy (Ancestors)

Hypertension, PulmonaryLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

CarbolinesPyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIndole AlkaloidsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds, 3-RingColloidsComplex MixturesDosage FormsPharmaceutical Preparations

Results Point of Contact

Title
Chief Medical Officer
Organization
Eli Lilly and Company
ClinicalTrials.gov@lilly.com
800-545-5979

Study Officials

  • 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

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 30, 2011

First Posted

December 2, 2011

Study Start

July 17, 2012

Primary Completion

April 21, 2017

Study Completion

April 3, 2019

Last Updated

October 9, 2019

Results First Posted

February 5, 2019

Record last verified: 2019-04

Data Sharing

IPD Sharing
Will share

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
• Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
More information

Locations

ES(2)PL(3)FR(3)US(5)CA(2)GB(1)