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Effects of Two Dosing Regimens of Bosentan in Children With Pulmonary Arterial Hypertension (FUTURE 3)

2017년 11월 7일 업데이트: Actelion

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

The primary objective of AC-052-373 was to assess the pharmacokinetic (PK) profile of two dosing regimens of the pediatric formulation of bosentan in children with pulmonary arterial hypertension (PAH) <12 years of age.

연구 개요

상태

완전한

정황

개입 / 치료

연구 유형

중재적

등록 (실제)

64

단계

  • 3단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 남아프리카
      • Bloemfontein, 남아프리카, 9300
        • Department of Paediatric Cardiology University of the Free State - Site 6001
      • Durban, 남아프리카, 4001
        • Paediatric Cardiology Albert Luthuli Central Hospital - Site 6003
      • Pretoria, 남아프리카, 0001
        • Division of Paediatric Cardiology, Steve Biko Academic Hospital - Site 6002
  • 네덜란드
      • Groningen, 네덜란드, 9713 GZ
        • Universitair Medish Centrum Groningen, Kindercardiologie - Site 1601
  • 독일
      • Berlin, 독일, 13353
        • Deutsches Herzzentrum Kinderkardiologie - Site 1401
      • Bonn, 독일, 53113
        • Universitätsklinikum Bonn Abteilung für Kinderkardiologie - Site 1404
      • Giessen, 독일, 35392
        • Justus-Liebig-Universität Giessen, Kinderherzzentrum - Site 1403
  • 러시아 연방
      • Kemerovo, 러시아 연방, 650002
        • RAMS Institution, Research Institute for complex issues of cardiovascular diseases, Siberian branch of the Russian Academy of Medical Sciences - Site 3805
      • Moscow, 러시아 연방, 121552
        • Scientific Center of Cardiovascular Surgery named after A.N.Bakulev of the RAMS - Site 3803
      • Moscow, 러시아 연방, 125412
        • Moscow Scientific Research Institute for Pediatrics and Childrens Surgery of Rosmedtechnologies - Site 3804
      • St. Petersberg, 러시아 연방, 197341
        • Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies" - Site 3802
      • St. Petersburg, 러시아 연방, 194100
        • State Educational Institution of Higher Professional Education "Saint Petersburg State Pediatric Medical Academy of Roszdrav" - Site 3801
  • 멕시코
      • Mexico City, 멕시코, 14080
        • Instituto Nacional de Cardiologia (INC) Ignacio Chavez - Site 8401
      • Monterrey, 멕시코, 64710
        • Unidad de Investigacion Clinica en Medicina, SC (UDICEM) - Site 8402
  • 미국
    • Colorado
      • Aurora, Colorado, 미국, 80045
        • The Children's Hospital - Site 9102
    • District of Columbia
      • Washington, District of Columbia, 미국, 20010
        • Children's National Medical Center - Site 9104
    • New York
      • New York, New York, 미국, 10032
        • Columbia University Medical Center Children's Hospital of New York Presbyterian - Site 9101
    • Texas
      • Houston, Texas, 미국, 77030
        • Texas Children's Hospital - Department of Cardiology - Site 9107
    • Washington
      • Seattle, Washington, 미국, 98105
        • Seattle Children's Hospital - Site 9106
  • 벨라루스
      • Minsk, 벨라루스, 220036
        • The Republican Scientific-Practical Center "Cardiology" - Site 3001
  • 세르비아
      • Belgrade, 세르비아, 11000
        • Univerzitetska dečja klinika, Služba za kardiologiju - Site 3901
      • Belgrade, 세르비아, 11070
        • Institut za zdravstvenu zaštitu majke i deteta Srbije "Dr Vukan Čupić", Služba za ispitivanje i lečenje bolesti srca i krvnih sudova - Site 3902
  • 스페인
      • Barcelona, 스페인, 08035
        • Hospital Universitatario Vall d'Hebron, Neumologia - Site 1907
      • Madrid, 스페인, 28046
        • Hospital Universitario La Paz - Paediatric Cardiology Department - Site 1906
  • 우크라이나
      • Dnepropetrovsk, 우크라이나, 49060
        • Clinical Diagnostic Center - Pediatric Cardiovascular and ANES and Intensive Care Department - Site 4103
      • Donetsk, 우크라이나, 83045
        • Gusak Ins Urgent and Recovery SUR AMS - Cardiovascular Rehabilitation Pediatric Department - Site 4101
      • Kiev, 우크라이나, 01135
        • Gover INS - Scientific Practical Cardiovascular Pediatric Center - MOH Ukraine - Site 4102
  • 이스라엘
      • Petach Tikvah, 이스라엘, 49202
        • Schneider Children's Medical Center- Institute of pediatric cardiology - Site 7101
  • 이탈리아
      • Padova, 이탈리아, 35128
        • Università Degli Studi di Padova - Dipartimento di Pediatria - Servizio di Cardiologia Pediatrica - Site 1501
      • Rome, 이탈리아, 00193
        • Ospedale Pediatrico "Bambino Gesù" - Dipartimento Medico Chirurgico di Cardiologia Pediatrica - Site 1502
  • 인도
      • Hyderabad, 인도, 500001
        • CARE Hospitals, Cardiology Dep. Hyderabad - Site 5302
      • New Delhi, 인도, 110076
        • Indraprashta Apollo Hospitals, Pediatric Cardiology - Site 5303
  • 중국
      • Beijing, 중국, 100029
        • Beijing Anzhen Hospital, Capital Medical University- Department of Pediatric Cardiology - Site 5103
      • Beijing, 중국, 100037
        • Cardiovascular Institute and Fuwai Hospital
      • Chengdu, 중국, 610041
        • West China 2nd university Hospital-Center of interventional diagnosis and therapy for Children's cardiovascular disease - Site 5104
      • Guangdong, 중국, 510080
        • Guangdong General Hospital - Site 5105
      • Shanghai, 중국, 200127
        • Shanghai Children's Medical Center - Site 5102
      • Shanghai, 중국, 200433
        • Shanghai Pulmonary Hospital, Department of Pulmonary Circulation - Site 5101
  • 체코
      • Prague, 체코, 150 06
        • Fakultní nemocnice v Motole, dětské kardiocentrum - Site 3301
  • 폴란드
      • Gdansk, 폴란드, 80-952
        • Uniwersyteckie Centrum Kliniczne Klinika Kardiologii Dziecięcej i Wad Wrodzonych Serca - Site 3604
      • Lodz, 폴란드, 93-336
        • Instytut Centrum Zdrowia Matki Polki Klinika Kardiologii ICMP w Lodz - Site 3602
      • Warszawa, 폴란드, 04-730
        • Instytut Pomnik - Centrum Zdrowia Dziecka Klinika Kardiologii Dziecięcej - Site 3601
      • Wroclaw, 폴란드, 51-124
        • Wojewódzki Szpital Specjalistyczny we Wrocławiu Oddział Kardiologii Dziecięcej z pododdziałem Intensywnego Nadzoru Kardiologicznego - Site 3605
  • 프랑스
      • Paris, 프랑스, 75743
        • Hopital Necker-Enfants Malades, Service de Cardiologie Pédiatrique - Site 2201
      • Toulouse, 프랑스, 31059
        • CHU de Toulouse - Hôpital des Enfants, Service de Cardiologie Pédiatrique - Site 2202
  • 헝가리
      • Budapest, 헝가리, 1096
        • Gottsegen György Országos Kardiológiai Intézet, Gyermekszív Központ, Gyermek Kardiológiai osztály - Site 3401
      • Szeged, 헝가리, 6720
        • Szegedi Tudományegyetem ÁOK Szent-Györgyi Albert Klinikai Központ, Gyermekgyógyászati Klinika és Gyermekegészségügyi Központ - Site 3402
  • 호주
      • Parkville, 호주, 3052
        • Royal Children's Hospital Melbourne, Cardiology - Site 5001

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

3개월 (어린이)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  1. 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)
  2. World Health Organization functional Class (WHO FC) I, II or III
  3. Male or female ≥ 3 months and < 12 years of age (maximum age at randomization is 11.5 years)
  4. Body weight ≥ 3.5 kg
  5. Peripheral oxygen saturation (SpO2) ≥ 88% (at rest, on room air)
  6. 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
  7. Signed informed consent by the parents or legal representatives

Exclusion Criteria:

  1. PAH etiologies other than listed above
  2. Non-stable disease status
  3. Need or plan to wean patient from intravenous epoprostenol or intravenous or inhaled iloprost
  4. Systolic blood pressure < 80% of the lower limit of normal range
  5. Aspartate aminotransferase and/or alanine aminotransferase values > 1.5 times the upper limit of normal range.
  6. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
  7. Hemoglobin and/or hematocrit levels < 75% of the lower limit of normal range.
  8. Known intolerance or hypersensitivity to bosentan or any of the excipients of the dispersible Tracleer tablet

  9. 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
  10. Treatment with another investigational drug within 1 month prior to randomization or planned treatment

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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
의약품: bosentan
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.
다른 이름들:
  • 추적자
  • 행위-050088
실험적: Bosentan 2 mg/Kg b.i.d.
2 mg/kg bosentan administered twice daily (morning and evening) for a planned duration of 24 weeks
의약품: bosentan
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.
다른 이름들:
  • 추적자
  • 행위-050088

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan
기간: 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

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

기타 결과 측정

결과 측정
측정값 설명
기간
Dose-corrected Maximum Plasma Concentration [Cmaxc] of Bosentan
기간: 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

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
Time to Reach Cmax [Tmax] of Bosentan
기간: 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

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
Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan Metabolites (Ro 478634, Ro 485033, Ro 641056)
기간: 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
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)].
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
Change From Baseline in WHO Functional Class at End of Study
기간: Baseline, up to Week 24 on average

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
Change From Baseline in Global Clincial Impression Scale (GCIS) at End of Study
기간: Baseline, up to Week 24 on average
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.
Baseline, up to Week 24 on average
Number of Patients With Treatment-emergent Liver Function Abnormalities
기간: Baseline, up to Week 24
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
Number of Patients With Treatment-emergent Hemoglobin Abnormalities
기간: Baseline, up to Week 24

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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Actelion

수사관

  • 연구 책임자: Andjela Kusic-Pajic, MD, Actelion

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2011년 3월 8일

기본 완료 (실제)

2013년 4월 3일

연구 완료 (실제)

2013년 8월 19일

연구 등록 날짜

최초 제출

2010년 10월 12일

QC 기준을 충족하는 최초 제출

2010년 10월 15일

처음 게시됨 (추정)

2010년 10월 19일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2017년 12월 11일

QC 기준을 충족하는 마지막 업데이트 제출

2017년 11월 7일

마지막으로 확인됨

2017년 11월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • AC-052-373

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

폐동맥 고혈압에 대한 임상 시험

bosentan에 대한 임상 시험

유사한 임상시험 검색

스폰서 및 공동 작업자

건강 상태

약물 개입

CROs by country

CROs in Brazil

정황

희귀 질병

약물 개입

식이 보충제

스폰서 / 협력자

위치

3
구독하다