- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT01223352
Effects of Two Dosing Regimens of Bosentan in Children With Pulmonary Arterial Hypertension (FUTURE 3)
An Open-label, Prospective Multicenter Study to Assess the Pharmacokinetics, Tolerability, Safety and Efficacy of the Pediatric Formulation of Bosentan Two Versus Three Times a Day in Children With Pulmonary Arterial Hypertension
Tutkimuksen yleiskatsaus
Opintotyyppi
Ilmoittautuminen (Todellinen)
Vaihe
- Vaihe 3
Yhteystiedot ja paikat
Opiskelupaikat
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Groningen, Alankomaat, 9713 GZ
- Universitair Medish Centrum Groningen, Kindercardiologie - Site 1601
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Parkville, Australia, 3052
- Royal Children's Hospital Melbourne, Cardiology - Site 5001
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Barcelona, Espanja, 08035
- Hospital Universitatario Vall d'Hebron, Neumologia - Site 1907
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Madrid, Espanja, 28046
- Hospital Universitario La Paz - Paediatric Cardiology Department - Site 1906
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Bloemfontein, Etelä-Afrikka, 9300
- Department of Paediatric Cardiology University of the Free State - Site 6001
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Durban, Etelä-Afrikka, 4001
- Paediatric Cardiology Albert Luthuli Central Hospital - Site 6003
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Pretoria, Etelä-Afrikka, 0001
- Division of Paediatric Cardiology, Steve Biko Academic Hospital - Site 6002
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Hyderabad, Intia, 500001
- CARE Hospitals, Cardiology Dep. Hyderabad - Site 5302
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New Delhi, Intia, 110076
- Indraprashta Apollo Hospitals, Pediatric Cardiology - Site 5303
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Petach Tikvah, Israel, 49202
- Schneider Children's Medical Center- Institute of pediatric cardiology - Site 7101
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Padova, Italia, 35128
- Università Degli Studi di Padova - Dipartimento di Pediatria - Servizio di Cardiologia Pediatrica - Site 1501
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Rome, Italia, 00193
- Ospedale Pediatrico "Bambino Gesù" - Dipartimento Medico Chirurgico di Cardiologia Pediatrica - Site 1502
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Beijing, Kiina, 100029
- Beijing Anzhen Hospital, Capital Medical University- Department of Pediatric Cardiology - Site 5103
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Beijing, Kiina, 100037
- Cardiovascular Institute and Fuwai Hospital
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Chengdu, Kiina, 610041
- West China 2nd university Hospital-Center of interventional diagnosis and therapy for Children's cardiovascular disease - Site 5104
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Guangdong, Kiina, 510080
- Guangdong General Hospital - Site 5105
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Shanghai, Kiina, 200127
- Shanghai Children's Medical Center - Site 5102
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Shanghai, Kiina, 200433
- Shanghai Pulmonary Hospital, Department of Pulmonary Circulation - Site 5101
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Mexico City, Meksiko, 14080
- Instituto Nacional de Cardiologia (INC) Ignacio Chavez - Site 8401
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Monterrey, Meksiko, 64710
- Unidad de Investigacion Clinica en Medicina, SC (UDICEM) - Site 8402
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Gdansk, Puola, 80-952
- Uniwersyteckie Centrum Kliniczne Klinika Kardiologii Dziecięcej i Wad Wrodzonych Serca - Site 3604
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Lodz, Puola, 93-336
- Instytut Centrum Zdrowia Matki Polki Klinika Kardiologii ICMP w Lodz - Site 3602
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Warszawa, Puola, 04-730
- Instytut Pomnik - Centrum Zdrowia Dziecka Klinika Kardiologii Dziecięcej - Site 3601
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Wroclaw, Puola, 51-124
- Wojewódzki Szpital Specjalistyczny we Wrocławiu Oddział Kardiologii Dziecięcej z pododdziałem Intensywnego Nadzoru Kardiologicznego - Site 3605
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Paris, Ranska, 75743
- Hopital Necker-Enfants Malades, Service de Cardiologie Pédiatrique - Site 2201
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Toulouse, Ranska, 31059
- CHU de Toulouse - Hôpital des Enfants, Service de Cardiologie Pédiatrique - Site 2202
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Berlin, Saksa, 13353
- Deutsches Herzzentrum Kinderkardiologie - Site 1401
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Bonn, Saksa, 53113
- Universitätsklinikum Bonn Abteilung für Kinderkardiologie - Site 1404
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Giessen, Saksa, 35392
- Justus-Liebig-Universität Giessen, Kinderherzzentrum - Site 1403
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Belgrade, Serbia, 11000
- Univerzitetska dečja klinika, Služba za kardiologiju - Site 3901
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Belgrade, Serbia, 11070
- Institut za zdravstvenu zaštitu majke i deteta Srbije "Dr Vukan Čupić", Služba za ispitivanje i lečenje bolesti srca i krvnih sudova - Site 3902
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Prague, Tšekki, 150 06
- Fakultní nemocnice v Motole, dětské kardiocentrum - Site 3301
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Dnepropetrovsk, Ukraina, 49060
- Clinical Diagnostic Center - Pediatric Cardiovascular and ANES and Intensive Care Department - Site 4103
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Donetsk, Ukraina, 83045
- Gusak Ins Urgent and Recovery SUR AMS - Cardiovascular Rehabilitation Pediatric Department - Site 4101
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Kiev, Ukraina, 01135
- Gover INS - Scientific Practical Cardiovascular Pediatric Center - MOH Ukraine - Site 4102
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Budapest, Unkari, 1096
- Gottsegen György Országos Kardiológiai Intézet, Gyermekszív Központ, Gyermek Kardiológiai osztály - Site 3401
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Szeged, Unkari, 6720
- Szegedi Tudományegyetem ÁOK Szent-Györgyi Albert Klinikai Központ, Gyermekgyógyászati Klinika és Gyermekegészségügyi Központ - Site 3402
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Minsk, Valko-Venäjä, 220036
- The Republican Scientific-Practical Center "Cardiology" - Site 3001
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Kemerovo, Venäjän federaatio, 650002
- RAMS Institution, Research Institute for complex issues of cardiovascular diseases, Siberian branch of the Russian Academy of Medical Sciences - Site 3805
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Moscow, Venäjän federaatio, 121552
- Scientific Center of Cardiovascular Surgery named after A.N.Bakulev of the RAMS - Site 3803
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Moscow, Venäjän federaatio, 125412
- Moscow Scientific Research Institute for Pediatrics and Childrens Surgery of Rosmedtechnologies - Site 3804
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St. Petersberg, Venäjän federaatio, 197341
- Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies" - Site 3802
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St. Petersburg, Venäjän federaatio, 194100
- State Educational Institution of Higher Professional Education "Saint Petersburg State Pediatric Medical Academy of Roszdrav" - Site 3801
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Colorado
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Aurora, Colorado, Yhdysvallat, 80045
- The Children's Hospital - Site 9102
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District of Columbia
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Washington, District of Columbia, Yhdysvallat, 20010
- Children's National Medical Center - Site 9104
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New York
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New York, New York, Yhdysvallat, 10032
- Columbia University Medical Center Children's Hospital of New York Presbyterian - Site 9101
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Texas
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Houston, Texas, Yhdysvallat, 77030
- Texas Children's Hospital - Department of Cardiology - Site 9107
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Washington
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Seattle, Washington, Yhdysvallat, 98105
- Seattle Children's Hospital - Site 9106
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
Inclusion Criteria:
PAH diagnosis confirmed with right heart catheterization (RHC):
- Idiopathic or heritable PAH, or
- Associated PAH persisting after complete repair of a congenital heart defect (PAH has to be persistent for at least 6 months after surgery) or
- PAH-Congenital Heart Disease (PAH-CHD) associated with systemic-to-pulmonary shunts (after global amendment dated 09 May 2012)
- World Health Organization functional Class (WHO FC) I, II or III
- Male or female ≥ 3 months and < 12 years of age (maximum age at randomization is 11.5 years)
- Body weight ≥ 3.5 kg
- Peripheral oxygen saturation (SpO2) ≥ 88% (at rest, on room air)
- Baseline PAH-therapy (Calcium channel blocker, bosentan, prostanoid, phosphodiesterase type-5 inhibitor) if present, has to be stable for at least 3 months prior to screening. During the study, all background treatments should remain stable
- Signed informed consent by the parents or legal representatives
Exclusion Criteria:
- PAH etiologies other than listed above
- Non-stable disease status
- Need or plan to wean patient from intravenous epoprostenol or intravenous or inhaled iloprost
- Systolic blood pressure < 80% of the lower limit of normal range
- Aspartate aminotransferase and/or alanine aminotransferase values > 1.5 times the upper limit of normal range.
- Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
- Hemoglobin and/or hematocrit levels < 75% of the lower limit of normal range.
- Known intolerance or hypersensitivity to bosentan or any of the excipients of the dispersible Tracleer tablet
Treatment with forbidden medication within 2 weeks or at least 5 times the half-life prior to randomization, whichever is the longest:
- Glibenclamide (glyburide)
- Cyclosporin A
- Sirolimus
- Tacrolimus
- Fluconazole
- Rifampicin (rifampin)
- Ritonavir
- Co-administration of CYP2C9 inhibitors (e.g., amiodarone, voriconazole) and moderate/strong CYP3A4 inhibitors (e.g., amprenavir, erythromycin, ketoconazole, diltiazem, itraconazole)
- Endothelin receptor antagonists (ERAs) other than bosentan
- Treatment with another investigational drug within 1 month prior to randomization or planned treatment
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: Bosentan 2 mg/Kg t.i.d.
2 mg/kg bosentan administered three times a day (morning, afternoon, evening) for a planned duration of 24 weeks
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32 mg quadrisected dispersible tablet.
The dosage of bosentan (2 mg/Kg) was adjusted according to the patient's body weight at initiation of the study treatment.
Dosage readjustment was permitted after 12 weeks of treatment.
Muut nimet:
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Kokeellinen: Bosentan 2 mg/Kg b.i.d.
2 mg/kg bosentan administered twice daily (morning and evening) for a planned duration of 24 weeks
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32 mg quadrisected dispersible tablet.
The dosage of bosentan (2 mg/Kg) was adjusted according to the patient's body weight at initiation of the study treatment.
Dosage readjustment was permitted after 12 weeks of treatment.
Muut nimet:
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan
Aikaikkuna: 0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment
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Daily exposure was measured by the area under the plasma concentration-time curve over a period of 24 hours [AUC(0-24)]. Concentrations of bosentan were measured directly in blood samples collected prior to study drug administration and up to 8 hours or up to 12 hours post-dose for the t.i.d and b.i.d. dosing regimen, respectively. AUC(0-24) was calculated as a multiple of AUCtau, which is the AUC over a dosing interval (AUCtau x 2 for the b.i.d. dosing regimen and AUCtau x 3 for the t.i.d. regimen). As the smallest dose unit was 8 mg (1/4 tablet), it was not possible to achieve the exact target dose of 2 mg/kg. Therefore, AUC(0-24) was corrected to 2 mg/kg (target dose) [AUC(0-24c)]. |
0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment
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Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Dose-corrected Maximum Plasma Concentration [Cmaxc] of Bosentan
Aikaikkuna: 0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment
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Concentrations of bosentan were measured directly in blood samples collected prior to study drug administration and up to 8 hours or up to 12 hours post-dose for the t.i.d and b.i.d. dosing regimen, respectively. The peak plasma concentration (Cmax) of bosentan was directly obtained from the measured plasma concentrations and was dose-corrected to the target dose of 2 mg/kg (Cmaxc). |
0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment
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Time to Reach Cmax [Tmax] of Bosentan
Aikaikkuna: 0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment
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Concentrations of bosentan were measured directly in blood samples collected prior to study drug administration and up to 8 hours or up to 12 hours post-dose for the t.i.d and b.i.d. dosing regimen, respectively. tmax was obtained directly from the measured plasma concentrations. |
0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment
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Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan Metabolites (Ro 478634, Ro 485033, Ro 641056)
Aikaikkuna: 0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment
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Concentrations of the metabolites were measured directly in blood samples collected prior to study drug administration and up to 8 hours or up to 12 hours post-dose for the t.i.d and b.i.d.
dosing regimen, respectively.
Daily exposure to the metabolites corresponds to the area under the concentration-time curve [AUC(0-24)] of the corresponding metabolite over a period of 24 hours, and was calculated in the same manner as the primary endpoint.
AUC(0-24c) was corrected to 2 mg/kg (target dose) [AUC(0-24c)].
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0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment
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Change From Baseline in WHO Functional Class at End of Study
Aikaikkuna: Baseline, up to Week 24 on average
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The World Health Organization (WHO) defines 4 classes to classify the functional status of patients with pulmonary hypertension (PH): Class I (FC I): No limitation of physical activity. Class II (FC II): Slight limitation of physical activity. Class IIII (FC III): Marked limitation of physical activity. Class IV (FC IV): Inability to carry out any physical activity without symptoms. Number of patients with improvement (shift from a higher to a lower class), worsening (shift from a lower to a higher class) or no change in WHO functional class at end of study compared to baseline are determined. |
Baseline, up to Week 24 on average
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Change From Baseline in Global Clincial Impression Scale (GCIS) at End of Study
Aikaikkuna: Baseline, up to Week 24 on average
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The GCIS is an assessment tool providing a single global assessment of the patient's current overall clinical condition: Very Good, Good, Neither Good or Bad, Bad and Very Bad.
The assessment was performed both by the physician and the parents / legal representatives independently.
Global clinical impression (GCI) at end of study was compared to GCI at baseline and the number of patients with clinical condition considered as worsened, improved or unchanged are determined.
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Baseline, up to Week 24 on average
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Number of Patients With Treatment-emergent Liver Function Abnormalities
Aikaikkuna: Baseline, up to Week 24
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Number of patients with increase in alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) above 3 times upper limit of normal (ULN).
The worst post-baseline value was considered.
The treatment-emergent period was defined as study treatment start date up to 7 calendar days after study treatment end date.
|
Baseline, up to Week 24
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Number of Patients With Treatment-emergent Hemoglobin Abnormalities
Aikaikkuna: Baseline, up to Week 24
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Number of patients with marked hemoglobin decreases (absolute values below 10 g/dL). The worst post-baseline value was considered. The treatment-emergent period was defined as study treatment start date up to 7 calendar days after study treatment end date. |
Baseline, up to Week 24
|
Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Opintojohtaja: Andjela Kusic-Pajic, MD, Actelion
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Arvio)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Sydän-ja verisuonitaudit
- Verisuonisairaudet
- Hengityselinten sairaudet
- Keuhkosairaudet
- Hypertensio, keuhko
- Hypertensio
- Keuhkovaltimon hypertensio
- Perinteinen primaarinen keuhkoverenpainetauti
- Farmakologisen vaikutuksen molekyylimekanismit
- Verenpainetta alentavat aineet
- Endoteliinireseptorin antagonistit
- Bosentaani
Muut tutkimustunnusnumerot
- AC-052-373
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
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Cytos Biotechnology AGValmisLievä essentiaalinen hypertensio | Kohtalainen essentiaalinen hypertensioSveitsi
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Istituto Auxologico ItalianoRekrytointiHypertensio, välttämätön | Hypertensio, hallitsematonArgentiina, Kiina