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ERA as specific PAH treatment

Phase 3

Hypertension, Pulmonary | Small molecule | Cardiovascular |Eli Lilly and Company|Last Updated: Nov 5, 2021

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment35
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01824290A Study of Tadalafil in Pediatric Participants With Pulmonary Arterial Hypertension (PAH)PHASE3 COMPLETED 35Feb 5, 2014Mar 10, 2021Nov 5, 202143 United States, Austria +12
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Study Endpoints
Primary Endpoints
Period 1: Change From Baseline to Week 24 in a 6 Minute Walk (MW) Distance in Meters
Baseline, Week 24

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.

Secondary Endpoints
Period 1: Time to Adjudicated Clinical Worsening (CW)
Baseline through Week 24
Period 1: Percentage of Participants Who Experience CW
Baseline through Week 24
Period 1: Pharmacokinetics (PK): Apparent Clearance (CL/F) of Tadalafil at Steady-state
Week 2, Week 4, Week 16 and Week 24
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
TadalafilEXPERIMENTALPeriod 1: 20 mg or 40 mg administered orally by tablets once a day. Period 2: 20 mg for middle weight and 40 mg for heavy weight administered orally by tablets once a day. Final tadalafil doses for Period 1 (6-month double-blind) were assigned after the weight cohort completion from H6D-MC-LVIG (NCT01484431).Tadalafil doses would range from 5 milligram (mg) to 40 mg depending on body weight cohorts. Heavy weight cohort ≥40 kilogram (kg), Middle weight cohort ≥25 kg to \<40 kg: administered orally by tablets once a day. Light weight cohort \<25 kg: administered orally by suspension once a day. Participants receiving tadalafil in Period 1 continued to receive tadalafil during Period 2 (2-year open-label extension).
PlaceboPLACEBO_COMPARATORPeriod 1: Participants received placebo orally by tablets once a day. Period 2: 20 mg for middle weight and 40 mg for heavy weight administered orally by tablets once a day. Final placebo dose for Period 1 (6-month double-blind) was be assigned after the weight cohort completion from H6D-MC-LVIG (NCT01484431) to maintain blinding depending on body weight cohort. Participants receiving placebo in Period 1 Period 2 (2-year open-label extension) would receive tadalafil in Period 2 at the corresponding tadalafil dose in that participant's weight group.
Interventions
NameTypeDescription
TadalafilDRUGAdministered orally by tablet form for heavy and middle weight participants. Administered orally by suspension for light weight participants.
PlaceboDRUGAdministered orally by tablet for heavy and middle weight participants. Administered orally by suspension for light weight participants.
ERA as specific PAH treatmentDRUGAll participants were taking endothelin receptor antagonist (ERA) (such as bosentan, ambrisentan and macitentan).
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Eligibility Criteria
Age Range6 Months — 17 Years
SexALL
Healthy VolunteersNo
Study Sites43

Inclusion Criteria: * ≥6 months to \<18 years of age at screening * Currently have a diagnosis of PAH that is either: * idiopathic, including hereditary * related to connective tissue disease * related to anorexigen use * associated with surgical repair of at least 6-month duration of cong...

Countries:United StatesAustriaBelgiumBrazilFranceGermanyIsraelItalyJapanMexicoNetherlandsPolandSpainTurkey (Türkiye)
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