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

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ClinicalTrials.gov Identifier: NCT01824290

Recruitment Status : Completed

First Posted : April 4, 2013

Results First Posted : March 23, 2020

Last Update Posted : November 5, 2021

Sponsor:

Information provided by (Responsible Party):

Eli Lilly and Company

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Hypertension, Pulmonary
Interventions	Drug: Tadalafil Drug: Placebo Drug: ERA as specific PAH treatment
Enrollment	35

Participant Flow

Recruitment Details
Pre-assignment Details	Per protocol and statistical analysis plan (SAP), the primary and secondary analysis from period 1 were performed to compare all tadalafil participants together versus all placebo participants together.


Arm/Group Title	Placebo	Tadalafil	Placebo/Tadalafil	Tadalafil/Tadalafil
Arm/Group Description	Period 1: Participants received pla...	Period 1: 20 mg middle weight cohor...	Period 2: 20 mg middle weight cohor...	Period 2: 20 mg middle weight cohor...
Arm/Group Description	Period 1: Participants received placebo orally by tablets once a day.	Period 1: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered tadalafil orally by tablets once a day.	Period 2: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered tadalafil orally by tablets once a day. Participants had received placebo during period 1.	Period 2: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered tadalafil orally by tablets once a day. Participants had received tadalafil during period 1.
Period Title: Period 1: Double Blind
Started	18	17	0	0
Received at Least One Dose of Study Drug	18	17	0	0
Received 20 mg	0	4	0	0
Received 40 mg	0	13	0	0
Completed	15	15	0	0
Not Completed	3	2	0	0
Reason Not Completed
Entry Criteria Not Met	1	0	0	0
Parent/Caregiver Decision	1	1	0	0
Investigator Reported Clinical Worsening	1	1	0	0
Period Title: Period 2: Open-Label Treatment
Started	0	0	16 ^[1]	16 ^[1]
Received 20 mg	0	0	3	3
Received 40 mg	0	0	13	13
Completed	0	0	13	13
Not Completed	0	0	3	3
Reason Not Completed
Adverse Event	0	0	0	1
Parent/caregiver Decision	0	0	1	1
Withdrawal by Subject	0	0	2	1
[1] As per the protocol, period 2 eligibility were participants who completed period 1 or experienced clinical worsening (CW) in period 1. 1 participant that had CW in period 1 continued to period 2.

Baseline Characteristics

Arm/Group Title		Placebo	Tadalafil	Total
Arm/Group Description		Period 1: Participants received pla...	Period 1: 20 mg middle weight cohor...	Total of all reporting groups
Arm/Group Description		Period 1: Participants received placebo orally by tablets once a day.	Period 1: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered orally by tablets once a day.	Total of all reporting groups
Overall Number of Baseline Participants		18	17	35
Baseline Analysis Population Description		...
Baseline Analysis Population Description		All participants who received at least one dose of study drug. Per protocol and statistical analysis plan (SAP), the primary and secondary analysis were performed to compare all tadalafil participants together versus all placebo participants together.
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	18 participants	17 participants	35 participants
		12.8 (3.39)	14.1 (3.49)	13.5 (3.45)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	18 participants	17 participants	35 participants
	Female	9	10	19
	Male	9	7	16
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	18 participants	17 participants	35 participants
	Hispanic or Latino	7	8	15
	Not Hispanic or Latino	6	4	10
	Unknown or Not Reported	5	5	10
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	18 participants	17 participants	35 participants
	American Indian or Alaska Native	1	3	4
	Asian	1	1	2
	Native Hawaiian or Other Pacific Islander	0	0	0
	Black or African American	2	1	3
	White	14	12	26
	More than one race	0	0	0
	Unknown or Not Reported	0	0	0
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	18 participants	17 participants	35 participants
Japan		1	1	2
Turkey		2	1	3
Brazil		9	6	15
Mexico		1	4	5
Israel		2	4	6
France		1	1	2
Germany		1	0	1
Poland		1	0	1
6 Minute Walk Distance Mean (Standard Deviation) Unit of measure: Meters
	Number Analyzed	18 participants	17 participants	35 participants
		476.7 (105.11)	485.8 (160.231)	481.1 (132.77)

Outcome Measures

1.Primary Outcome


Title	Period 1: Change From Baseline to Week 24 in a 6 Minute Walk (MW) Distance in Meters
Description	6MWD in meters assessed in a subset of participants who are ≥6 t...
Description	6MWD in meters assessed in a subset of participants who are ≥6 to <18 years of age who are developmentally capable of performing a 6MW test. Change from baseline was derived using mixed model repeated measures (MMRM) with terms for treatment group, visit, baseline 6MWD, and treatment-by-visit interaction.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug who were > = 6 to < 18 years of age and were capable of performing a 6MW test.


Arm/Group Title	Placebo	Tadalafil
Arm/Group Description:	Period 1: Participants received pla...	Period 1: 20 mg middle weight cohor...
Arm/Group Description:	Period 1: Participants received placebo orally by tablets once a day.	Period 1: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered orally by tablets once a day.
Overall Number of Participants Analyzed	15	15
Least Squares Mean (Standard Error) Unit of Measure: Meters
	36.60 (20.776)	60.48 (20.410)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tadalafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	23.88
	Confidence Interval	(2-Sided) 80% -14.25 to 62.00
	Parameter Dispersion	Type: Standard Error of the Mean Value: 29.114
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Period 1: Time to Adjudicated Clinical Worsening (CW)
Description	Clinical worsening was defined as any of the following: death,lung or ...
Description	Clinical worsening was defined as any of the following: death,lung or heart transplantation,atrial septostomy or Potts' shunt,hospitalization for Pulmonary Arterial Hypertension(PAH) progression,new onset syncope,initiation of new PAH therapy(including increase in the dose of existing PAH specific concomitant therapy,such as endothelin receptor agonist or beraprost medication), or increase of 1 or more in World Health Organization(WHO) Functional Class(except for participants already in Class IV;only for participants unable to perform the 6 minute walk(6MW) test;worsening of WHO functional class by 1 or more for participants who can perform a 6 minute walk(6MW) test and who have a decrease of ≥ 20% in the 6 minute walk distance(for those participants who are ≥6 years of age). Criteria for CW(from Period 1) were adjudicated by an independent,blinded study-specific Clinical Endpoint Committee(CEC).This adjudication was used for data analysis, and was not used to guide subject treatment.
Time Frame	Baseline through Week 24

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.


Arm/Group Title	Placebo	Tadalafil
Arm/Group Description:	Period 1: Participants received pla...	Period 1: 20 mg middle weight cohor...
Arm/Group Description:	Period 1: Participants received placebo orally by tablets once a day.	Period 1: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered orally by tablets once a day.
Overall Number of Participants Analyzed	18	17
Median (95% Confidence Interval) Unit of Measure: Weeks
	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)

[1]

There was no confirmed adjudicated CW case to report.

3.Secondary Outcome


Title	Period 1: Percentage of Participants Who Experience CW
Description	Clinical worsening was defined as any of the following: death,lung or ...
Description	Clinical worsening was defined as any of the following: death,lung or heart transplantation,atrial septostomy or Potts' shunt,hospitalization for Pulmonary Arterial Hypertension(PAH) progression,new onset syncope, initiation of new PAH therapy(including increase in the dose of existing PAH specific concomitant therapy,such as endothelin receptor agonist or beraprost medication),or increase of 1 or more in World Health Organization(WHO) Functional Class(except for participants already in Class IV; only for participants unable to perform the 6 minute walk(6MW) test;worsening of WHO functional class by 1 or more for participants who can perform a 6 minute walk(6MW) test and who have a decrease of ≥ 20% in the 6 minute walk distance(for those participants who are ≥6 years of age).Criteria for CW(from Period 1) were adjudicated by an independent,blinded study-specific Clinical Endpoint Committee(CEC).This adjudication was used for data analysis, and was not used to guide subject treatment.
Time Frame	Baseline through Week 24

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.


Arm/Group Title	Placebo	Tadalafil
Arm/Group Description:	Period 1: Participants received pla...	Period 1: 20 mg middle weight cohor...
Arm/Group Description:	Period 1: Participants received placebo orally by tablets once a day.	Period 1: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered orally by tablets once a day.
Overall Number of Participants Analyzed	18	17
Measure Type: Number Unit of Measure: percentage of participants
	0	0

4.Secondary Outcome


Title	Period 1: Pharmacokinetics (PK): Apparent Clearance (CL/F) of Tadalafil at Steady-state
Description	Period 1: Pharmacokinetics (PK): Apparent Clearance (CL/F) of Tadalafi...
Description	Period 1: Pharmacokinetics (PK): Apparent Clearance (CL/F) of Tadalafil at steady-state
Time Frame	Week 2, Week 4, Week 16 and Week 24

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.


Arm/Group Title		20 mg Tadalafil	40 mg Tadalafil
Arm/Group Description:		Period 1: 20 mg tadalafil administe...	Period 1: 40 mg tadalafil administe...
Arm/Group Description:		Period 1: 20 mg tadalafil administered orally by tablets once a day with concomitant endothelin receptor antagonist (ERA).	Period 1: 40 mg tadalafil administered orally by tablets once a day with concomitant ERA.
Overall Number of Participants Analyzed		4	13
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: Liter Per Hour (L/hr)
With concomitant bosentan	Number Analyzed	3 participants	13 participants
With concomitant bosentan		3.63 (38.1%)	4.49 (28.2%)
No bosentan (ERA: Macitentan)	Number Analyzed	1 participants	0 participants
No bosentan (ERA: Macitentan)		NA ^[1] (NA%)

[1]

For n = 1, geometric mean and geometric coefficient of variation could not be calculated. Individual value is 2.68.

5.Secondary Outcome


Title	Period 2: Percentage of Participants Who Experience CW
Description	Clinical worsening was defined as any of the following: death, lung or...
Description	Clinical worsening was defined as any of the following: death, lung or heart transplantation, atrial septostomy or Potts' shunt, hospitalization for Pulmonary Arterial Hypertension (PAH) progression, new onset syncope, initiation of new PAH therapy (including increase in the dose of existing PAH specific concomitant therapy, such as endothelin receptor agonist or beraprost medication), or increase of 1 or more in World Health Organization(WHO) Functional Class (except for participants already in Class IV; only for participants unable to perform the 6 minute walk (6MW) test; worsening of WHO functional class by 1 or more for participants who can perform a 6 minute walk (6MW) test and who have a decrease of ≥ 20% in the 6 minute walk distance (for those participants who are ≥6 years of age).
Time Frame	Period 2 Baseline through Study Completion (Up to 24 Months)

Outcome Measure Data

Analysis Population Description

Period 2: All participants who received at least one dose of study drug.


Arm/Group Title	Placebo/Tadalafil - Open-Label Treatment	Tadalafil/Tadalafil - Open-Label Treatment
Arm/Group Description:	Period 2: 20 mg middle weight cohor...	Period 2: 20 mg middle weight cohor...
Arm/Group Description:	Period 2: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered tadalafil orally by tablets once a day. Participants had received placebo during period 1.	Period 2: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered tadalafil orally by tablets once a day. Participants had received tadalafil during period 1.
Overall Number of Participants Analyzed	16	16
Measure Type: Number Unit of Measure: percentage of participants
	12.5	18.8

6.Secondary Outcome


Title	Period 2: Time to First Occurrence of CW
Description	Clinical worsening was defined as any of the following: death, lung or...
Description	Clinical worsening was defined as any of the following: death, lung or heart transplantation, atrial septostomy or Potts' shunt, hospitalization for Pulmonary Arterial Hypertension (PAH) progression, new onset syncope, initiation of new PAH therapy (including increase in the dose of existing PAH specific concomitant therapy, such as endothelin receptor agonist or beraprost medication), or increase of 1 or more in World Health Organization(WHO) Functional Class (except for participants already in Class IV; only for participants unable to perform the 6 minute walk (6MW) test; worsening of WHO functional class by 1 or more for participants who can perform a 6 minute walk (6MW) test and who have a decrease of ≥ 20% in the 6 minute walk distance (for those participants who are ≥6 years of age).
Time Frame	Period 2 Baseline through Study Completion (Up to 24 Months)

Outcome Measure Data

Analysis Population Description

Period 2: All participants who received at least one dose of study drug, who entered the open-label treatment Period


Arm/Group Title	Placebo/Tadalafil - Open-Label Treatment	Tadalafil/Tadalafil - Open-Label Treatment
Arm/Group Description:	Period 2: 20 mg middle weight cohor...	Period 2: 20 mg middle weight cohor...
Arm/Group Description:	Period 2: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered tadalafil orally by tablets once a day. Participants had received placebo during period 1.	Period 2: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered tadalafil orally by tablets once a day. Participants had received tadalafil during period 1.
Overall Number of Participants Analyzed	16	16
Median (95% Confidence Interval) Unit of Measure: Months
	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)

[1]

Median and CI are not estimable due to inadequate events of Clinical Worsening (CW) using Kaplan-Meier survival Estimates.

Adverse Events

Time Frame	Baseline Up To 24 Months
Adverse Event Reporting Description	All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.

Arm/Group Title	Placebo - Double Blind		Tadalafil - Double Blind		Placebo/Tadalafil - Open-Label Treatment		Tadalafil/Tadalafil - Open-Label Treatment
Arm/Group Description	Period 1: Participants received pla...		Period 1: 20 mg middle weight cohor...		Period 2: 20 mg middle weight cohor...		Period 2: 20 mg middle weight cohor...
Arm/Group Description	Period 1: Participants received placebo orally by tablets once a day.		Period 1: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered tadalafil orally by tablets once a day.		Period 2: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered tadalafil orally by tablets once a day. Participants had received placebo during period 1.		Period 2: 20 mg middle weight cohort or 40 mg for heavy weight cohort administered tadalafil orally by tablets once a day. Participants had received tadalafil during period 1.
All-Cause Mortality
	Placebo - Double Blind		Tadalafil - Double Blind		Placebo/Tadalafil - Open-Label Treatment		Tadalafil/Tadalafil - Open-Label Treatment
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/18 (0.00%)		0/17 (0.00%)		0/16 (0.00%)		0/16 (0.00%)
Serious Adverse Events Serious Adverse Events
	Placebo - Double Blind		Tadalafil - Double Blind		Placebo/Tadalafil - Open-Label Treatment		Tadalafil/Tadalafil - Open-Label Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0.00%)		0/17 (0.00%)		4/16 (25.00%)		1/16 (6.25%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Cardiac disorders
Acute right ventricular failure ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Infections and infestations
Gastroenteritis ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Pneumonia ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Haemoptysis ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
1 Term from vocabulary, MedDRA 24.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo - Double Blind		Tadalafil - Double Blind		Placebo/Tadalafil - Open-Label Treatment		Tadalafil/Tadalafil - Open-Label Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/18 (44.44%)		15/17 (88.24%)		11/16 (68.75%)		12/16 (75.00%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	2/16 (12.50%)	2	0/16 (0.00%)	0
Eosinophilia ^† 1	1/18 (5.56%)	1	0/17 (0.00%)	0	0/16 (0.00%)	0	0/16 (0.00%)	0
Cardiac disorders
Palpitations ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
Supraventricular tachycardia ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Tachycardia ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
Ventricular extrasystoles ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Ear and labyrinth disorders
Ear pain ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Eye disorders
Asthenopia ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Photopsia ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Gastrointestinal disorders
Abdominal pain upper ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	2/16 (12.50%)	2
Dental caries ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Enterocolitis ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Gastrooesophageal reflux disease ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Irritable bowel syndrome ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Nausea ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Plicated tongue ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Vomiting ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	3/16 (18.75%)	3
General disorders
Asthenia ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Exercise tolerance decreased ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Pyrexia ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
Immune system disorders
Hypersensitivity ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Seasonal allergy ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	2
Infections and infestations
Acute sinusitis ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	2/16 (12.50%)	2	0/16 (0.00%)	0
Ascariasis ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Body tinea ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Bronchitis ^† 1	1/18 (5.56%)	1	0/17 (0.00%)	0	0/16 (0.00%)	0	0/16 (0.00%)	0
Ear infection ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	2
Gastroenteritis ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Impetigo ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Influenza ^† 1	0/18 (0.00%)	0	3/17 (17.65%)	3	0/16 (0.00%)	0	1/16 (6.25%)	1
Nasopharyngitis ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	2	3/16 (18.75%)	4
Otitis media acute ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Paronychia ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Pharyngitis ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	2/16 (12.50%)	4
Rhinitis ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	2/16 (12.50%)	2	0/16 (0.00%)	0
Sinusitis ^† 1	1/18 (5.56%)	1	1/17 (5.88%)	1	0/16 (0.00%)	0	1/16 (6.25%)	2
Tonsillitis ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Tracheobronchitis ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Upper respiratory tract infection ^† 1	1/18 (5.56%)	1	3/17 (17.65%)	3	0/16 (0.00%)	0	2/16 (12.50%)	2
Urinary tract infection ^† 1	1/18 (5.56%)	1	1/17 (5.88%)	1	0/16 (0.00%)	0	1/16 (6.25%)	1
Vaginal infection ^† 1	0/9 (0.00%)	0	1/10 (10.00%)	1	0/8 (0.00%)	0	0/10 (0.00%)	0
Viral infection ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Viral tonsillitis ^† 1	1/18 (5.56%)	1	0/17 (0.00%)	0	0/16 (0.00%)	0	0/16 (0.00%)	0
Viral upper respiratory tract infection ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
Injury, poisoning and procedural complications
Bone contusion ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
Penis injury ^† 1	0/9 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0
Investigations
Blood creatine phosphokinase increased ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Hepatic enzyme increased ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Dyslipidaemia ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Vitamin b12 deficiency ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Vitamin d deficiency ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/18 (5.56%)	1	2/17 (11.76%)	2	0/16 (0.00%)	0	2/16 (12.50%)	2
Back pain ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
Musculoskeletal chest pain ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Pain in extremity ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Patellofemoral pain syndrome ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pharyngeal neoplasm ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Nervous system disorders
Dizziness ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	3/16 (18.75%)	3
Headache ^† 1	2/18 (11.11%)	6	5/17 (29.41%)	5	2/16 (12.50%)	2	3/16 (18.75%)	3
Presyncope ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	1/16 (6.25%)	1
Somnolence ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
Syncope ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Psychiatric disorders
Anxiety ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Excessive masturbation ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Insomnia ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Reproductive system and breast disorders
Menorrhagia ^† 1	0/9 (0.00%)	0	1/10 (10.00%)	1	1/8 (12.50%)	1	1/10 (10.00%)	2
Metrorrhagia ^† 1	0/9 (0.00%)	0	0/10 (0.00%)	0	0/8 (0.00%)	0	1/10 (10.00%)	1
Penis disorder ^† 1	0/9 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0	0/6 (0.00%)	0
Polymenorrhoea ^† 1	0/9 (0.00%)	0	0/10 (0.00%)	0	0/8 (0.00%)	0	1/10 (10.00%)	1
Spontaneous penile erection ^† 1	0/9 (0.00%)	0	1/7 (14.29%)	2	1/8 (12.50%)	1	0/6 (0.00%)	0
Uterine haemorrhage ^† 1	0/9 (0.00%)	0	0/10 (0.00%)	0	1/8 (12.50%)	1	0/10 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Dyspnoea ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Epistaxis ^† 1	1/18 (5.56%)	1	2/17 (11.76%)	2	1/16 (6.25%)	1	1/16 (6.25%)	1
Oropharyngeal pain ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	1/16 (6.25%)	1
Pulmonary arterial hypertension ^† 1	1/18 (5.56%)	1	0/17 (0.00%)	0	0/16 (0.00%)	0	0/16 (0.00%)	0
Respiratory distress ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Skin and subcutaneous tissue disorders
Dermatitis allergic ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	2
Haemorrhage subcutaneous ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	3	0/16 (0.00%)	0	0/16 (0.00%)	0
Livedo reticularis ^† 1	1/18 (5.56%)	1	0/17 (0.00%)	0	0/16 (0.00%)	0	0/16 (0.00%)	0
Photosensitivity reaction ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Pruritus ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	1/16 (6.25%)	1	0/16 (0.00%)	0
Rash ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
Swelling face ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
Social circumstances
Menarche ^† 1	1/9 (11.11%)	1	0/10 (0.00%)	0	0/8 (0.00%)	0	0/10 (0.00%)	0
Vascular disorders
Deep vein thrombosis ^† 1	0/18 (0.00%)	0	0/17 (0.00%)	0	0/16 (0.00%)	0	1/16 (6.25%)	1
Flushing ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
Hypotension ^† 1	0/18 (0.00%)	0	1/17 (5.88%)	1	0/16 (0.00%)	0	0/16 (0.00%)	0
1 Term from vocabulary, MedDRA 24.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

The study is mainly descriptive in a small number of children with PAH and there were no participants enrolled in the light weight cohort.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Chief Medical Officer
Organization:	Eli Lilly and Company
Phone:	800-545-5979
EMail:	ClinicalTrials.gov@lilly.com

Layout table for additonal information

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT01824290
Other Study ID Numbers:	10609 H6D-MC-LVHV ( Other Identifier: Eli Lilly and Company ) 2012-002354-23 ( EudraCT Number )
First Submitted:	April 1, 2013
First Posted:	April 4, 2013
Results First Submitted:	March 6, 2020
Results First Posted:	March 23, 2020
Last Update Posted:	November 5, 2021

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