Study the Safety and Effectiveness of Tadalafil on High Blood Pressure in the Blood Vessel Going From the Heart to the Lungs

Study Overview
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Brief Summary
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Study to determine the long term safety of tadalafil in patients with increased blood pressure in the blood vessel that carries blood from the right heart to the lungs and to see if it will keep the disease from getting worse.

Official Title
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An Extension Study to Evaluate the Long-Term Safety and Efficacy of the Phosphodiesterase Type 5 (PDE5) Inhibitor Tadalafil in the Treatment of Patients With Pulmonary Arterial Hypertension

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Drug: tadalafil
* Drug: tadalafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have participated and discontinued in the previous PAH placebo controlled study due to clinical worsening on placebo or tadalafil 2.5 mg, 10mg, or 20 mg Must have completed Week 16 of the previous PAH study and had either no clinical worsening or became clinically worse at the Week 16 visit on placebo or tadalafil 2.5 mg, 10mg, or 20 mg Females who have a negative urine pregnancy test and are willing to use 2 types of birth control Be 12 years or older (country specific regulations apply) with parental approval Exclusion Criteria: Participated in the placebo controlled study and had clinical worsening on 40 mg tadalafil Have left-sided heart disease Have a musculoskeletal disorder that limits being able to get around Nitrate use Certain current systemic treatments

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 20 mg tadalafil<br>20 milligram (mg) tadalafil taken once a day | Drug: tadalafil<br>* 20 milligram (mg) tablet, taken by mouth once a day for 52 weeks for the phase 1 portion. Open label phase includes 40 mg tablet taken by mouth once a day until the sponsor concludes the study or tadalafil becomes commercially available for the treatment of Pulmonary Arterial Hypertension (PAH).<br>* Other names: IC351;|
| Active Comparator: 40 mg tadalafil<br>40 mg tadalafil tablet taken once a day | Drug: tadalafil<br>* 40 mg tablet taken by mouth once a day for 52 weeks in phase 1. Open label phase includes 40 mg tablet taken by mouth once a day until the sponsor concludes the study or tadalafil becomes commercially available for the treatment of PAH.<br>* Other names: IC351;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | A summary of serious and all other non-serious AEs, which include adverse events reported for laboratory tests and vital signs, is located in the Reported Adverse Event module. | Baseline (Double-Blind Period) up to Week 243 (End of Open-Label Period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-Minute Walk Distance (6MWD) at Baseline and Weeks 16, 28, 40 and 52 | 6MWD measured the distance a participant was able to walk unassisted in 6 minutes. | Baseline and Weeks 16, 28, 40 and 52 | 
| Borg Dyspnea Assessment at Baseline and Weeks 16, 28, 40 and 52 | Borg dyspnea score is a participant rated measure of their greatest degree of shortness of breath during exertion (6-minute walk test). Score ranged from 0 (nothing at all) to 10 (very, very severe [maximal]). | Baseline and Weeks 16, 28, 40 and 52 | 
| Probability of No Pulmonary Arterial Hypertension (PAH) Deterioration at Weeks 16, 28, 40 and up to 52 | World Health Organization Functional Classification Assessment (WHO FC) is a method of classifying disease severity in PAH. The classes are: Class I: pulmonary hypertension (PH) but without resulting limitation of physical activity, Class II: PH resulting in slight limitation of physical activity, Class III: PH resulting in marked limitation of physical activity, Class IV: PH with inability to carry out any physical activity without symptoms. Deterioration of WHO FC is defined as moving to a higher WHO FC within one visit. Results are presented as Kaplan-Meier estimates (% probability) of remaining free from WHO FC deterioration after a given time. | Baseline and Weeks 16, 28, 40 and 52 |