A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension

Study Purpose

Selexipag is available for the treatment of pulmonary arterial hypertension (PAH) in adults in various countries. The efficacy of selexipag to delay disease progression was shown in a previous pivotal study conducted in 1156 adult patients with PAH. Given the similarities in the functional changes of PAH in children and adults, it is expected that children suffering from PAH could benefit from treatment with selexipag. The aim of the present study is to confirm the doses of selexipag to be used in pediatric patients with PAH older than 2 years. To fulfill this aim, blood levels of selexipag (pharmacokinetic assessments) as well as the safety, and tolerability of selexipag in children with PAH will be assessed.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 2 Years - 18 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Signed and dated informed consent by the parent(s) or Legally authorized representative(s) AND assent from developmentally capable children.
  • - Males or females between ≥ 2 and < 18 years of age with weight ≥ 9 kg.
  • - PAH diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before subject's enrollment - PAH with one of the following etiologies: - idiopathic (iPAH), - heritable (hPAH), - associated with congenital heart disease (CHD): PAH with co-incidental CHD; post-operative PAH (persisting/ recurring/ developing ≥ 6 months after repair of CHD) - Drug or toxin-induced - PAH associated with HIV - PAH associated with connective tissue disease - Word Health Organization functional class (WHO FC) II to III.
  • - Subjects treated with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor provided that the treatment dose(s) has been stable for at least 3 months prior to enrollment, or patients who are not candidates for these therapies.
  • - Females of childbearing potential must have a negative pregnancy test at Screening and at Enrollment, and must agree to undertake monthly pregnancy tests, and to use a reliable method of contraception (if sexually active) from screening up to study drug discontinuation plus 30 days (EOS).
Key

Exclusion Criteria:

  • - Subjects with PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis.
  • - Subjects with PAH associated with Eisenmenger syndrome.
  • - Subjects with moderate to large left-to-right shunts.
  • - Subjects with cyanotic congenital cardiac lesions such as transposition of the great arteries, truncus arteriosus, univentricular heart or pulmonary atresia with ventricular septal defect, as well as subjects with Fontan-palliation.
  • - Subjects with pulmonary hypertension due to lung disease.
  • - Previous treatment with Uptravi (selexipag) within 2 weeks prior to enrollment.
  • - Subjects having received prostacyclin (epoprostenol) or prostacyclin analogs (i.e., treprostinil, iloprost, beraprost) within 2 months prior to enrollment or are scheduled to receive any of these compounds during the trial.
  • - Treatment with another investigational drug within 4 weeks prior to enrollment.
  • - History, or current suspicion of intussusception or ileus or gastrointestinal obstruction as per investigator's judgment.
  • - Uncontrolled thyroid disease as per investigator judgment.
  • - Hemoglobin or hematocrit < 75% of the lower limit of normal range.
  • - Known severe or moderate hepatic impairment.
  • - Clinical signs of hypotension that in the investigator's judgment would preclude initiation of a PAH-specific therapy.
  • - Subjects with severe renal insufficiency.
  • - Known hypersensitivity to the investigational treatment or to any of the excipients of the drug formulations.
  • - History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study treatment(s) (e.g., cholecystectomy).
  • - Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03492177
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Actelion
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Sofija Cerovic
Principal Investigator Affiliation Actelion
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Belarus, Canada, China, France, Germany, Hungary, Israel, Malaysia, Poland, Russian Federation, Serbia, Taiwan, Ukraine, United Kingdom, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Pulmonary Arterial Hypertension
Study Website: View Trial Website
Additional Details

The selection of the starting dose for pediatric patients is based on the pharmacokinetic (PK) extrapolation from adults, taking into account the children body weight category, in order to lead to an exposure similar to that in adult PAH patients at a starting dose of 200 microgram (μg). As in adults, selexipag will be up-titrated to the individual maximum tolerated dose (iMTD) during the first 12 weeks. Approximately 55 subjects will be enrolled in 3 different age cohorts to obtain at least 40 subjects with evaluable PK profiles: Cohort 1: ≥ 12 to < 18 years of age, Cohort 2: ≥ 6 to < 12 years of age, Cohort 3: ≥ 2 to < 6 years of age. In each age cohort the starting dose will depend on the body weight. Enrollment will start with both Cohort 1 and Cohort 2. After completion of PK assessments in at least 15 subjects from Cohort 1 at Week 12, a first interim analysis will be conducted to establish the dose-exposure relationship using a population PK model. Results of this model-based analysis will be used to confirm or adjust the selexipag doses initially selected. Enrollment of Cohort 3 (children ≥ 2 to < 6 years of age) will start once the appropriate doses have been confirmed in a second interim analysis of PK data from Cohorts 1 and 2, and if there is no safety concern based on review by an Independent Data Monitoring Committee (IDMC).

Arms & Interventions

Arms

Experimental: open label selexipag

The first dose of selexipag (Uptravi) will be administered in the evening of Day 1 and will be based on the body weight. Thereafter selexipag will be administered twice daily (morning and evening). Selexipag will be up-titrated during the first 12 weeks, with weekly increments equal to the starting dose until the subjects reach their individual maximum tolerated dose (iMTD) or until a maximum dose corresponding to their baseline weight category is achieved (which will be 8-fold of the corresponding starting dose). Up-titration is followed by a stable maintenance treatment period from Week 12 to Week 16, at the maximum tolerated dose. Thereafter, subjects will be treated with selexipag as long as the treatment is beneficial to the subject, as per investigator's decision

Interventions

Drug: - selexipag (Uptravi)

Film-coated tablets for oral administration

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Aurora, Colorado

Status

Recruiting

Address

Children'S Hospital Cardiac Care Center University Of Colorado

Aurora, Colorado, 80045

University of Iowa Hospital, Iowa City, Iowa

Status

Completed

Address

University of Iowa Hospital

Iowa City, Iowa, 52242

Mayo Clinic, Rochester, Minnesota

Status

Withdrawn

Address

Mayo Clinic

Rochester, Minnesota, 55905

Columbia University Medical Center, New York, New York

Status

Withdrawn

Address

Columbia University Medical Center

New York, New York, 10032

Vanderbilt University Medical Center, Nashville, Tennessee

Status

Not yet recruiting

Address

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-2386

Seattle Children's Hospital, Seattle, Washington

Status

Recruiting

Address

Seattle Children's Hospital

Seattle, Washington, 98105

International Sites

Minsk, Belarus

Status

Recruiting

Address

State Institution Republican Scientific And Practical Center For Pediatric Surgery

Minsk, , 220013

Minsk, Belarus

Status

Recruiting

Address

Health Institution 4Th City Children'S Clinical Hospital

Minsk, , 220118

Centre Hospitalier Sainte Justine, Montreal, Quebec, Canada

Status

Not yet recruiting

Address

Centre Hospitalier Sainte Justine

Montreal, Quebec, H3T 1C4

Stollery Children's Hospital, Edmonton, Canada

Status

Withdrawn

Address

Stollery Children's Hospital

Edmonton, , AB T6G 2C8

Beijing Anzhen Hospital, Beijing, China

Status

Not yet recruiting

Address

Beijing Anzhen Hospital

Beijing, , 100029

Beijing, China

Status

Not yet recruiting

Address

Cardiovascular institute & Fuwai Hospital- Thrombus Center

Beijing, , 100037

Guangdong Provincial People's Hospital, Guangzhou, China

Status

Not yet recruiting

Address

Guangdong Provincial People's Hospital

Guangzhou, , 510080

Shanghai Children's Medical Center, Shanghai, China

Status

Recruiting

Address

Shanghai Children's Medical Center

Shanghai, , 200127

Wuhan Asia Heart Hospital, Wuhan, China

Status

Not yet recruiting

Address

Wuhan Asia Heart Hospital

Wuhan, , 430022

CHU Arnaud de Villeneuve, Montpellier Cedex 5, France

Status

Recruiting

Address

CHU Arnaud de Villeneuve

Montpellier Cedex 5, , 34295

Hôpital Necker - Enfants Malades, Paris, France

Status

Recruiting

Address

Hôpital Necker - Enfants Malades

Paris, , 75015

Chu Hopital Des Enfants, Toulouse Cedex 9, France

Status

Recruiting

Address

Chu Hopital Des Enfants

Toulouse Cedex 9, , 31059

Universitätsklinikum Freiburg Zentrum, Freiburg, Germany

Status

Recruiting

Address

Universitätsklinikum Freiburg Zentrum

Freiburg, , 70106

Giessen, Germany

Status

Not yet recruiting

Address

Justus-Liebig-Universität Gießen, Kinderherzzentrum

Giessen, , 35392

Universitäres Herzzentrum Hamburg, Hamburg, Germany

Status

Withdrawn

Address

Universitäres Herzzentrum Hamburg

Hamburg, , 20246

Universitätsklinikum Münster, Münster, Germany

Status

Withdrawn

Address

Universitätsklinikum Münster

Münster, , 48149

Budapest, Hungary

Status

Recruiting

Address

Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály

Budapest, , 1096

Schneider Children's Medical Center, Petach Tikvah, Israel

Status

Recruiting

Address

Schneider Children's Medical Center

Petach Tikvah, ,

Sheba Medical Center, Ramat Gan, Israel

Status

Recruiting

Address

Sheba Medical Center

Ramat Gan, , 52621

Sarawak General Hospital, Kota Samarahan, Malaysia

Status

Recruiting

Address

Sarawak General Hospital

Kota Samarahan, , 94300

Kuala Lumpur, Malaysia

Status

Recruiting

Address

Institut Jantung Negara (National Heart Institute)

Kuala Lumpur, , 50400

Uniwersyteckie Centrum Kliniczne, Gdańsk, Poland

Status

Withdrawn

Address

Uniwersyteckie Centrum Kliniczne

Gdańsk, , 80-952

Kraków, Poland

Status

Withdrawn

Address

Uniwersytecki Szpital Dzieciecy w Krakowie

Kraków, , 30-663

Szpital Kliniczny im. Karola Jonschera, Poznan, Poland

Status

Withdrawn

Address

Szpital Kliniczny im. Karola Jonschera

Poznan, , 60-572

Wrocław, Poland

Status

Completed

Address

Wojewódzki Szpital Specjalistyczny We Wrocławiu

Wrocław, , 51-124

Kazan State Medical University, Kazan, Russian Federation

Status

Recruiting

Address

Kazan State Medical University

Kazan, , 420059

Kemerovo, Russian Federation

Status

Recruiting

Address

Federal State Budget Scientific Institution

Kemerovo, , 650002

Moscow, Russian Federation

Status

Recruiting

Address

Moscow Scientific Research Institute For Pediatrics And Childrens Surgery Of Rosmedtechnologies

Moscow, , 125412

Samara, Russian Federation

Status

Recruiting

Address

Samara Regional Clinical Cardiological Dispensary

Samara, , 443070

Federal State Budgetary Institution, St Petersburg, Russian Federation

Status

Recruiting

Address

Federal State Budgetary Institution

St Petersburg, , 197341

Univerzitetska Dečja Klinika, Belgrade, Serbia

Status

Recruiting

Address

Univerzitetska Dečja Klinika

Belgrade, , 11000

Belgrade, Serbia

Status

Recruiting

Address

Institut Za Zdravstvenu Zaštitu Majke I Deteta Srbije ''Dr Vukan Čupić''

Belgrade, , 11070

National Cheng Kung University Hospital, Tainan, Taiwan

Status

Recruiting

Address

National Cheng Kung University Hospital

Tainan, , 704

National Taiwan University Hospital, Taipei, Taiwan

Status

Recruiting

Address

National Taiwan University Hospital

Taipei, , 100

Dnipro, Ukraine

Status

Recruiting

Address

Municipal Enterprise Of The Dnipropetrovsk Regional Council

Dnipro, , 49070

Kiev, Ukraine

Status

Recruiting

Address

State Institution Of The Ministry Of Health Of Ukraine

Kiev, , 04050

Lviv Regional Clinical Hospital, Lviv, Ukraine

Status

Recruiting

Address

Lviv Regional Clinical Hospital

Lviv, , 79010

Zaporizhzhya, Ukraine

Status

Recruiting

Address

Municipal Institution Of The Zaporizhzhya Regional Council

Zaporizhzhya, , 69063

Great Ormond Street Hospital, London, United Kingdom

Status

Recruiting

Address

Great Ormond Street Hospital

London, , WC1N 3JH

For more information, please contact PHA at Research@PHAssociation.org and refer to the terms of service below.

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