Riociguat in Children With Pulmonary Arterial Hypertension (PAH)

ID: NCT02562235
Status: Recruiting
Phase: Phase 3
Start Date: October 29, 2015
First Submitted: September 28, 2015
Last Updated: February 22, 2018
Results: N/A
Organization: Bayer
Sponsors & Collaborators: Bayer, Merck Sharp & Dohme Corp.
Location: Belgium, Colombia, France, Germany, Hungary, Italy, Japan, Mexico, Netherlands, Poland, Romania, Spain, Taiwan, Turkey, United Kingdom, United States
Conditions: Hypertension, Pulmonary
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Study Description

Brief Summary

This study is designed to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of riociguat at age-, sex- and body-weight-adjusted doses of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID in children from ≥6 to less than 18 years with pulmonary arterial hypertension (PAH) group 1. The study consists of two phases: titration phase up to 8 weeks and a maintenance phase up to 16 weeks.

Detailed Description

Condition or disease Intervention/treatment Phase

Hypertension, Pulmonary

Drug: Riociguat (Adempas, BAY63-2521)
Other Names
Phase 3

Tracking Information

First Submitted DateSeptember 28, 2015
Last Update Posted DateFebruary 22, 2018
Actual Start DateOctober 29, 2015
Anticipated Completion DateNovember 25, 2031
Actual Primary Completion DateJune 12, 2020
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Change in incidence of treatment-emergent adverse events [Time Frame: Baseline to week 24]

  • Change in incidence of treatment-emergent serious adverse events [Time Frame: Baseline to week 24]

  • Change in heart rate [Time Frame: Baseline to week 24]

  • Change in blood pressure [Time Frame: Baseline to week 24]

  • Change in bone age x-ray of left hand [Time Frame: Baseline to week 24]

  • Plasma concentration of riociguat [Time Frame: Day 0, Day 1 (0.5, 1.5 and 2.5h), Day 28, Day 56]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Change in 6-Minute Walking Distance (6MWD) [Time Frame: Baseline to week 24]

  • Change in WHO functional class [Time Frame: Baseline to week 24]

  • Change in NT-proBNP or BNP (N-terminal pro-brain natriuretic peptide) [Time Frame: Baseline to week 24]

  • Changes in echocardiograph from baseline [Time Frame: Baseline to week 24]

  • Time to clinical worsening [Time Frame: Baseline to week 24]

  • Change in Quality of Life scores as assessed by patient questionnaire and PedsQL generic score [Time Frame: Baseline to week 24]

    Parent questionnaire and in children able to understand questions

  • Questionnaire to assess both taste and texture of pediatric formulation(s) [Time Frame: Baseline to week 24]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleRiociguat in Children With Pulmonary Arterial Hypertension (PAH)
Official TitleOpen-label, Individual Dose Titration Study to Evaluate Safety, Tolerability and Pharmacokinetics of Riociguat in Children From 6 to Less Than 18 Years of Age With Pulmonary Arterial Hypertension (PAH)
Brief Summary

This study is designed to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of riociguat at age-, sex- and body-weight-adjusted doses of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID in children from ≥6 to less than 18 years with pulmonary arterial hypertension (PAH) group 1. The study consists of two phases: titration phase up to 8 weeks and a maintenance phase up to 16 weeks.

Detailed Description

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
23
Allocation
Not Available
Interventional Model
Single Group Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Hypertension, Pulmonary
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Riociguat (Adempas, BAY63-2521)

The individual optimal (maintenance) dose is to be determined based on patients' monitoring of systolic blood pressure, well-being and clinical status.

Other Names
Study Groups/Cohorts
Riociguat
Body-weight adjusted dose equivalent to the exposure of (0.5mg) 1.0 - 2.5 mg three times a day (TID), individual dose titration (IDT) in adults treated for PAH.

Study Arms
Experimental Riociguat
Body-weight adjusted dose equivalent to the exposure of (0.5mg) 1.0 - 2.5 mg three times a day (TID), individual dose titration (IDT) in adults treated for PAH.
Drug : Riociguat (Adempas, BAY63-2521)
The individual optimal (maintenance) dose is to be determined based on patients' monitoring of systolic blood pressure, well-being and clinical status.

Arm Intervention/Treatment
Experimental Riociguat
Body-weight adjusted dose equivalent to the exposure of (0.5mg) 1.0 - 2.5 mg three times a day (TID), individual dose titration (IDT) in adults treated for PAH.
Drug : Riociguat (Adempas, BAY63-2521)

Recruitment Information

Recruitment Status:Recruiting
Enrollment23
Completion DateNovember 25, 2031
Eligibility Criteria: Inclusion Criteria:
- Children aged ≥6 to <18 years
- Diagnosed with PAH :
- Idiopathic (IPAH)
- Hereditable (HPAH)
- PAH associated with (APAH)
- Connective tissue disease
- Congenital heart disease with shunt closure more than 6 months ago (no open shunts, confirmed by RHC no less than 4 months after surgery)
- Diagnosis of PAH confirmed by right heart catheterization (RHC) at any time prior to enrolment (for patients with closed shunts - RHC no less than 4 months after surgery)
- Pulmonary arterial hypertension confirmed by a RHC at any time prior to start of study, with mean pulmonary artery pressure (PAPmean) ≥25 mmHg at rest, pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) ≤15 mmHg, and pulmonary vascular resistance (PVR) >240 dyn•sec•cm-5 (i.e., ≥3.0 wood units•m2)
- Patients must be on standard of care PAH medications, allowing Endothelin Receptor Antagonists (ERA) and/or Prostacyclin Analogues (PCA), for at least 12 weeks prior to baseline visit.
- Two groups of patients will be included:
- Prevalent: Patients currently on monotherapy who need additional treatment (discretion of the investigator)
- Incident: Treatment naïve patients initiated on PAH medication (allowing ERA and /or PCA) and then riociguat added once patinets are stable on standard of care
- WHO functional class I-III
- Adolescent females of childbearing potential can only be included in the study if a pregnancy test is negative. Adolescent females of childbearing potential must agree to use adequate contraception when sexually active. 'Adequate contraception' is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Adequate contraception is required from the signing of the informed consent form up until 6 weeks after the last study drug administration.
- Young men must agree to use adequate contraception when sexually active.
- Written inform consent provided and if applicable child assent provided

Exclusion Criteria:
- Concomitant use of the following medications: phosphodiesterase (PDE) 5 inhibitors (such as sildenafil, tadalafil, vardenafil) and non-specific phosphodiesterase (PDE) inhibitors (theophylline, dipyridamole), nitrates or NO donors (such as amyl nitrite) in any form
- Pretreatment with NO donors (e.g. nitrates) within the last 2-weeks before visit 1
- Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization or any history of bronchial artery embolization or massive hemoptysis within 3 months prior to screening
- Systolic blood pressure (SBP) more than 5 mmHg lower than the age-, sex- and height-adapted level of the 50th SBP percentile (NHBPEP, 2004)
- History of left-sided heart disease, including valvular disease or heart failure
- Pulmonary hypertension related to conditions other than specified in the inclusion criteria
- Pulmonary veno-occlusive disease
- Screening aspartate transaminase (AST) and/ or alanine transaminase (ALT) more than 3 times the upper limit of normal (ULN)
- Severe restrictive lung disease
- Severe congenital abnormalities of the lung, thorax, and diaphragm
- Clinically relevant hepatic dysfunction (especially Child Pugh C)
- Renal insufficiency (estimated glomerular filtration rate <30 mL/min/1.73m2 e.g. calculated based on Schwartz formula, for detailed calculation instructions
- PH associated with idiopathic interstitial pneumonia (PH-IIP)
GenderAll
Age6 Years to 17 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Belgium
Colombia
France
Germany
Hungary
Italy
Japan
Mexico
Netherlands
Poland
Romania
Spain
Taiwan
Turkey
United Kingdom
United States

Administrative Information

NCT Number:NCT02562235
Other Study ID Numbers
15681
2014-003952-29
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Bayer
Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director
Bayer Study Director
Bayer