Clinical Study to Assess the Long-term Safety, Tolerability, and Efficacy of Macitentan in Subjects With Eisenmenger Syndrome - Clinical Trial for Pulmonary Arterial Hypertension | NCT01739400

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Primary Purpose

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Macitentan 10 mg tablet, once daily.

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Eisenmenger Syndrome, exercise capacity

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects with ES (including those with Down Syndrome) having completed the double-blind AC-055-305 / MAESTRO study as scheduled, i.e., who remained in the double-blind study up to Week 16 (whether or not they were still taking study drug at the end of this period).

Exclusion Criteria:

Subjects who prematurely discontinue double-blind study drug during the AC-055-305 / MAESTRO study due to:

an AE assessed as related to the use of study drug,
or elevated liver tests (related or unrelated to study drug).

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Macitentan

Arm Description

Macitentan 10 mg tablet, once daily.

Outcomes

Primary Outcome Measures

Change in Exercise Capacity as Measured by 6-minute Walking Distance (6MWD) Month 6 and 12

NOTE: The MAESTRO-OL study was exploratory in nature and no primary efficacy and safety endpoint were defined in the clinical protocol. This and the other exploratory efficacy outcome measures posted were selected to be reported as a primary endpoints. All efficacy analyses were considered exploratory. The analyses of the exploratory efficacy endpoints focused on the absolute values and on the change from DB baseline to Week 16 in the DB study and to Month 6 and Month 12 in the OL study. For missing 6MWD values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a distance of zero (0) meters was imputed for all 6MWD visits from the date of death. For any other reasons, the last available value was carried forward.

Change in WHO Functional Class (FC) at Month 6 and 12

Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing stairs). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure. For missing WHO FC values in the OL study, the following imputation rules were applied: If the reason for missing data was death, class IV was imputed for all WHO visits from the date of death. For any other reasons, the last available value was carried forward.

Change in Borg Dyspnea Score at Month 6 and 12

The Borg dyspnea score rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). For missing Borg dyspnea index values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a value of 10 was imputed for all Borg visits from the date of death. For any other reasons, the last available value was carried forward.

Change in Peripheral Oxygen Saturation (SpO2) at Rest at Month 6 and 12

No imputation of missing data for SpO2 was applied. Oxygen saturation assessed by pulse oximetry: peripheral oxygen saturation (SpO2) at rest before the 6-minute walk test (6MWT)

Secondary Outcome Measures

Full Information

NCT ID

NCT01739400

First Posted

November 29, 2012

Last Updated

March 26, 2019

Sponsor

Actelion

1. Study Identification

Unique Protocol Identification Number

NCT01739400

Brief Title

Clinical Study to Assess the Long-term Safety, Tolerability, and Efficacy of Macitentan in Subjects With Eisenmenger Syndrome

Acronym

MAESTRO-OL

Official Title

Long Term, Single-arm, Open-label Extension Study of Protocol AC-055-305 to Assess the Safety, Tolerability and Efficacy of Macitentan in Subjects With Eisenmenger Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Terminated

Why Stopped

Primary endpoint of parent study AC-055-305/MAESTRO (NCT01743001) not met.

Study Start Date

September 10, 2013 (Actual)

Primary Completion Date

January 12, 2018 (Actual)

Study Completion Date

January 12, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Actelion

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Long-term study to evaluate if macitentan is safe, tolerable and efficient enough to be used for treatment of Eisenmenger syndrome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Arterial Hypertension

Keywords

Eisenmenger Syndrome, exercise capacity

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

217 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Macitentan

Arm Type

Experimental

Arm Description

Macitentan 10 mg tablet, once daily.

Intervention Type

Drug

Intervention Name(s)

Macitentan 10 mg tablet, once daily.

Other Intervention Name(s)

Macitentan, ACT-064992

Intervention Description

Macitentan 10 mg tablet, once daily.

Primary Outcome Measure Information:

Title

Change in Exercise Capacity as Measured by 6-minute Walking Distance (6MWD) Month 6 and 12

Description

NOTE: The MAESTRO-OL study was exploratory in nature and no primary efficacy and safety endpoint were defined in the clinical protocol. This and the other exploratory efficacy outcome measures posted were selected to be reported as a primary endpoints. All efficacy analyses were considered exploratory. The analyses of the exploratory efficacy endpoints focused on the absolute values and on the change from DB baseline to Week 16 in the DB study and to Month 6 and Month 12 in the OL study. For missing 6MWD values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a distance of zero (0) meters was imputed for all 6MWD visits from the date of death. For any other reasons, the last available value was carried forward.

Time Frame

From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.

Title

Change in WHO Functional Class (FC) at Month 6 and 12

Description

Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing stairs). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure. For missing WHO FC values in the OL study, the following imputation rules were applied: If the reason for missing data was death, class IV was imputed for all WHO visits from the date of death. For any other reasons, the last available value was carried forward.

Time Frame

From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.

Title

Change in Borg Dyspnea Score at Month 6 and 12

Description

The Borg dyspnea score rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). For missing Borg dyspnea index values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a value of 10 was imputed for all Borg visits from the date of death. For any other reasons, the last available value was carried forward.

Time Frame

From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.

Title

Change in Peripheral Oxygen Saturation (SpO2) at Rest at Month 6 and 12

Description

No imputation of missing data for SpO2 was applied. Oxygen saturation assessed by pulse oximetry: peripheral oxygen saturation (SpO2) at rest before the 6-minute walk test (6MWT)

Time Frame

From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Subjects with ES (including those with Down Syndrome) having completed the double-blind AC-055-305 / MAESTRO study as scheduled, i.e., who remained in the double-blind study up to Week 16 (whether or not they were still taking study drug at the end of this period). Exclusion Criteria: Subjects who prematurely discontinue double-blind study drug during the AC-055-305 / MAESTRO study due to: an AE assessed as related to the use of study drug, or elevated liver tests (related or unrelated to study drug).

Facility Information:

Facility Name

Emory University Hospital/the Emory Clinic

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Barnes-Jewish Hosp/Wash Univ School of Med

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Children'S Heart Center Nevada

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89109

Country

United States

Facility Name

Nationwide Children's Hospital

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Facility Name

Texas Children'S Hosp - Dept of Cardiology

City

Houston

State/Province

Texas

ZIP/Postal Code

77030-2303

Country

United States

Facility Name

Gen Hosp Univ Vienna Dept Cardiology

City

Vienna

ZIP/Postal Code

A-1090

Country

Austria

Facility Name

Mhat Nat Card Hosp - Cardiology Clinic

City

Sofia

ZIP/Postal Code

1309

Country

Bulgaria

Facility Name

Mhat Nat Card Hosp - Pediatric Clin / Ped Card Dept

City

Sofia

ZIP/Postal Code

1309

Country

Bulgaria

Facility Name

Mhat Sveta Anna Clin Card

City

Sofia

ZIP/Postal Code

1750

Country

Bulgaria

Facility Name

Instituto Nacional del Torax

City

Providencia

State/Province

Santiago RCH

ZIP/Postal Code

7500691

Country

Chile

Facility Name

Clinica Tabancura - Cardio Unit

City

Santiago

ZIP/Postal Code

7650018

Country

Chile

Facility Name

Guangdong General Hospital, Cardiology Dpt

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

Facility Name

Wu Han Asia Heart Hosp

City

Wuhan

State/Province

Hubei

ZIP/Postal Code

430022

Country

China

Facility Name

The General Hosp of Shenyang Military Region

City

Shenyang

State/Province

Liaoning

ZIP/Postal Code

110016

Country

China

Facility Name

Beijing Anzhen Hospital, Cardiology Dpt

City

Beijing

ZIP/Postal Code

100029

Country

China

Facility Name

Cardiovascular Institute&Fuwai Hospital

City

Beijing

ZIP/Postal Code

100037

Country

China

Facility Name

Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation

City

Shanghai

ZIP/Postal Code

200433

Country

China

Facility Name

Hosp La Timone - Dept Pediatric Cardiology

City

Marseille Cedex 5

ZIP/Postal Code

13385

Country

France

Facility Name

Hosp Laennec - Dept Cardiology

City

Nantes Cedex 1

ZIP/Postal Code

44093

Country

France

Facility Name

Hosp Pompidou - Dept Congenital Cardiac Diseases

City

Paris cedex 15

ZIP/Postal Code

75908

Country

France

Facility Name

Hosp Cardiology Haut Leveque - Dept Congenital Diseases

City

Pessac

ZIP/Postal Code

33604

Country

France

Facility Name

Herzzentrum Berlin, Ped Cardiology

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Universitätsklinikum Giessen - Pediatric Heart Center

City

Giessen

ZIP/Postal Code

35392

Country

Germany

Facility Name

Uni Heidelberg - Kinderkardiologie

City

Heidelberg

ZIP/Postal Code

D-69120

Country

Germany

Facility Name

Ahepa University General Hospital

City

Thessaloniki

ZIP/Postal Code

54636

Country

Greece

Facility Name

Institut Jantung Negara

City

Kuala Lumpur

ZIP/Postal Code

50400

Country

Malaysia

Facility Name

Unidad de Investigacion Clin En Med, Sc (Udicem)

City

Monterrey

State/Province

Nuevo Leon

ZIP/Postal Code

64718

Country

Mexico

Facility Name

Instituto Nacional de Cardiologia (Inc) Ignacio Chavez

City

Mexico City

ZIP/Postal Code

14080

Country

Mexico

Facility Name

Instituto de Corazon de Querètaro

City

Querétaro

Country

Mexico

Facility Name

PHC, MAB

City

Manila

Country

Philippines

Facility Name

Cardiology Gdańsk Univ

City

Gdańsk

ZIP/Postal Code

80-952

Country

Poland

Facility Name

Cardiology Kraków Univ

City

Krakow

ZIP/Postal Code

31-202

Country

Poland

Facility Name

Cardiology Wrocław

City

Wrocław

ZIP/Postal Code

51-124

Country

Poland

Facility Name

Hosp Univ Coimbra - Dpt Cardiology

City

Coimbra

ZIP/Postal Code

3000-075

Country

Portugal

Facility Name

Hosp Sta Marta - Dept Cardiology

City

Lisboa

ZIP/Postal Code

1169-024

Country

Portugal

Facility Name

Er Inst For Cardvasc Dis "Prof Dr Cc Iliescu" - Card Ii

City

Bucaresti

ZIP/Postal Code

022328

Country

Romania

Facility Name

Cardio Med Srl

City

Targu-Mures

ZIP/Postal Code

540136

Country

Romania

Facility Name

Clin Hosp For Inf and Pulm Dis Victor Babes - Ii Pulm

City

Timisoara

ZIP/Postal Code

300312

Country

Romania

Facility Name

Sci Institute Systemic Poriblems Cardio Diseases Kemerovo

City

Kemerovo

ZIP/Postal Code

650002

Country

Russian Federation

Facility Name

Russian Cardiology Scientific and Production Complex

City

Moscow

ZIP/Postal Code

121552

Country

Russian Federation

Facility Name

V. A. Almazov Institute of Cardiology

City

St Petersburg

ZIP/Postal Code

194156

Country

Russian Federation

Facility Name

Dedinje Cardiovasc Inst - Cardiovasc Research Ctr

City

Belgrade

ZIP/Postal Code

11040

Country

Serbia

Facility Name

Mother and Child Health Care Institute Dr. Vukan Cupic

City

Belgrade

ZIP/Postal Code

11070

Country

Serbia

Facility Name

Clin Hosp Ctr Zemun - Cardiology Dept

City

Belgrade

ZIP/Postal Code

11080

Country

Serbia

Facility Name

Hosp Univ Vall D'Hebron - Dpt Congenital Heart Disease Adult

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Hosp Univ Virgen Macarena - Dpt Cardiology

City

Sevilla

ZIP/Postal Code

41007

Country

Spain

Facility Name

Hosp Universitario La Fe Dpt Cardiology

City

Valencia

ZIP/Postal Code

46009

Country

Spain

Facility Name

Bristol Univ Hosp Congenital Heart Centre

City

Bristol

ZIP/Postal Code

BS2 8BJ

Country

United Kingdom

Facility Name

Hanoi Medical University Hospital

City

Hanoi

Country

Vietnam

Facility Name

Children'S Hospital, Ho Chi Minh

City

Ho Chi Minh

Country

Vietnam

Facility Name

Tam Duc Hospital

City

Ho Chi Minh

Country

Vietnam

Clinical Study to Assess the Long-term Safety, Tolerability, and Efficacy of Macitentan in Subjects With Eisenmenger Syndrome (MAESTRO-OL)

Pulmonary Arterial Hypertension

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial