Ambrisentan for Inoperable Chronic Thromboembolic Pulmonary Hypertension.

NCT01884675 | Terminated Phase 3 Results DMC

• 1 other identifier: 115811
• Study Type: interventional
• Target: 33
• Locations: 16 countries
• Sites: 51

Brief Summary

It is hypothesised that ambrisentan may provide benefit to subjects with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), where currently no proven or licensed treatment options exist. This Phase III, randomized, double-blind placebo controlled parallel group, 16 week study will compare the safety and efficacy of ambrisentan 5 milligrams (mg) versus placebo in subjects with inoperable CTEPH. The study will enrol 160 subjects, to assure at least 72 evaluable subjects per treatment arm, based on 10% drop-out rate.

Conditions

Hypertension

Keywords

Endothelin Receptor Antagonist; Inoperable Chronic Thromboembolic Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Six Minutes Walking Distance (6MWD) at Week 16

  The 6-minute walk test was conducted according to the American Thoracic Society guidelines in accordance with local standard operating procedures. 6MWD was measured by a 6-minute walk test. This test measures the distance that a participant can walk in a period of 6 minutes. Change from baseline was calculated at Weeks 4, 8, 12 and 16. Change from Baseline was calculated as value at the specified visit minus the Baseline value. Data at Baseline is based on average of two consecutive test results during Screening/Baseline period that differ by \<10%. If only one measurement was available, that measurement was used. In any cases where the protocol-defined criteria for Baseline 6MWD was not met, the Baseline value was based on the last two consecutive measurements for a participant.

  Baseline (Week 0); Weeks 4, 8, 12 and 16/Early Withdrawal

Secondary Outcomes (17)

• Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 16

  Baseline (Week 0) and Week 16

• Change From Baseline in WHO Functional Class (FC) at Weeks 4, 8, 12 and 16/Early Withdrawal

  Baseline (Week 0); Weeks 4, 8, 12 and 16/Early Withdrawal

• Change From Baseline in Borg CR10 Scale (BCR10S) Immediately Following Exercise at Weeks 4, 8, 12 and 16/Early Withdrawal

  Baseline (Week 0); Weeks 4, 8, 12 and 16/Early Withdrawal

• Number of Participants With Clinical Worsening of Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

  From randomization to Week 16/Follow up visit (21 weeks)

• Change From Baseline in Mean Right Atrial Pressure (mRAP) and Mean Pulmonary Artery Pressure (mPAP) at Week 16

  Baseline (Week 0) and Week 16

Study Arms (2)

Ambrisentan

EXPERIMENTAL

Subjects in this arm will receive ambrisentan 5 mg tablet once daily during the treatment period.

Drug: Ambrisentan 5 mg

Placebo

PLACEBO COMPARATOR

Subjects in this arm will receive ambrisentan-matching placebo tablet once daily during the treatment period.

Drug: Placebo

Interventions

Ambrisentan 5 mg DRUG

White, film-coated, immediate-release tablets, containing 5 mg ambrisentan for single dose oral.

Ambrisentan

Placebo DRUG

White, film-coated, ambrisentan-matching placebo tablet for single oral dose

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent prior to beginning study-related procedures.
• Subject must be between 18-80 years of age, inclusive, at the Screening Visit.
• Subjects must have a diagnosis of CTEPH at an expert centre with a positive V/Q and CT angiogram and a pulmonary angiogram if available within 6 months prior to screening.
• Subject must meet all of the following haemodynamic criteria by means of a RHC within 3 months prior to screening: Mean pulmonary artery pressure (mPAP) of \>25 millimeters of mercury (mmHg), Pulmonary vascular resistance (PVR) \>400 dynes.sec/centimetre (cm)\^5, Pulmonary capillary wedge pressure (PCWP) or Left ventricle end diastolic pressure (LVEDP) of \<15 mmHg.
• Subjects must have previously been judged inoperable due to the obstruction being surgically inaccessible (i.e. distal disease) by an expert multidisciplinary team which must include at least one cardiology or respiratory consultant, and one consultant PEA surgeon. For countries with CTEPH expert centers \[including at least a surgeon with sound experience performing Pulmonary Endarterectomy (PEAs)\] the expert team will be the local expert centre. For countries without a CTEPH surgical expert center a central adjudication committee will assess the operability of the subjects during the screening period.
• Subject must walk a distance of \>150 Meters (m) and \< 475 m at the screening visit.
• Subject must have a current diagnosis of being in WHO Functional Class II or III.
• Subject, with or without supplemental oxygen, must have a resting arterial oxygen saturation (SaO2) \> 92% as measured by pulse oximetry at the Screening Visit.
• Subjects must have received anticoagulation for a minimum of 3 months prior to Screening
• Female subject of childbearing potential must agree to use 2 reliable methods of contraception from the Screening Visit until study completion and for at least 30 days following the last dose of Investigational Product
• Subject must agree not to participate in a clinical study involving another investigational drug or device throughout this study.
• Subject must be competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent form (ICF) and must sign the form prior to the initiation of any study procedures.

You may not qualify if:

• Subject received previous Pulmonary arterial hypertension (PAH) therapy (Phosphodiesterase type 5 \[PDE5i\], Endothelin receptor antagonist \[ERA\], chronic prostanoid use)
• Subject has previously discontinued other ERA in either another clinical study or commercial product for safety or tolerability reasons other than for liver function abnormalities.
• Subject has a known hypersensitivity to the Investigational Products, the metabolites, or formulation excipients
• Subject has previously undergone a pulmonary endarterectomy or a balloon pulmonary angioplasty
• Subject receiving intravenous inotropes within 2 weeks prior to the Screening Visit (e.g. dopamine, dobutamine)
• Subjects receiving Calcium Channel Blockers or 5-hydroxy-3-methylglutaryl-coenzyme A 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) on an unstable dose 4 weeks prior to the Screening Visit (to be eligible subjects must not have changed their dose \<4 weeks prior to the screening visit)
• Subject has not enrolled in an exercise training program for cardiopulmonary rehabilitation within 12 weeks prior to the Screening Visit and must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 16 weeks of the study. Subjects enrolled in an exercise program for pulmonary rehabilitation 12 weeks prior to screening may enter the study if they agree to maintain their current level of rehabilitation for the first 16 weeks of the study.
• Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) \> 3x Upper limit of normal (ULN)
• Bilirubin \> 1.5xULN (\>35% direct bilirubin)
• Subject has severe renal impairment \[estimated creatinine clearance \<30 millilitre/minute (mL/min)\] at the Screening Visit
• Subject has moderate - severe hepatic impairment (Child-Pugh class B-C with or without cirrhosis) at the Screening Visit
• Subject has clinically significant anaemia: Hemoglobin (Hb) \< 10 grams/decilitre (g/dL)
• Subjects with bleeding disorders or significant active peptic ulceration in the opinion of the investigator
• Subject has uncontrolled hypertension (\>180/110 mmHg) at screening
• Subject has severe hypotension (\<90/50 mmHg) at screening

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (51)

GSK Investigational Site

Boston, Massachusetts, 02118, United States

Location

GSK Investigational Site

Dallas, Texas, 75390-8550, United States

Location

GSK Investigational Site

Corrientes, Corrientes Province, W3400AMZ, Argentina

Location

GSK Investigational Site

Rosario, Santa Fe Province, S2000ODA, Argentina

Location

GSK Investigational Site

Santa Fe, Santa Fe Province, Argentina

Location

GSK Investigational Site

Buenos Aires, C1181ACH, Argentina

Location

GSK Investigational Site

Graz, A-8036, Austria

Location

GSK Investigational Site

Innsbruck, A-6020, Austria

Location

GSK Investigational Site

Vienna, 1090, Austria

Location

GSK Investigational Site

Edmonton, Alberta, T6G 2G3, Canada

Location

GSK Investigational Site

London, Ontario, N6A 5W9, Canada

Location

GSK Investigational Site

Wuhan, Hubei, 430022, China

Location

GSK Investigational Site

Xi'an, Shaanxi, 710061, China

Location

GSK Investigational Site

Beijing, 100020, China

Location

GSK Investigational Site

Beijing, 100037, China

Location

GSK Investigational Site

Beijing, 100038, China

Location

GSK Investigational Site

Shanghai, 200433, China

Location

GSK Investigational Site

Prague, 128 08, Czechia

Location

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

GSK Investigational Site

Regensburg, Bavaria, 93053, Germany

Location

GSK Investigational Site

Würzburg, Bavaria, 97074, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Homburg, Saarland, 66421, Germany

Location

GSK Investigational Site

Dresden, Saxony, 01307, Germany

Location

GSK Investigational Site

Leipzig, Saxony, 04103, Germany

Location

GSK Investigational Site

Ashkelon, 78360, Israel

Location

GSK Investigational Site

Zrifin, 70300, Israel

Location

GSK Investigational Site

Aichi, 466-8560, Japan

Location

GSK Investigational Site

Fukuoka, 812-8582, Japan

Location

GSK Investigational Site

Hokkaido, 060-8648, Japan

Location

GSK Investigational Site

Hyōgo, 650-0017, Japan

Location

GSK Investigational Site

Miyagi, 980-8574, Japan

Location

GSK Investigational Site

Tochigi, 329-0498, Japan

Location

GSK Investigational Site

Tokyo, 113-8655, Japan

Location

GSK Investigational Site

Tokyo, 181-8611, Japan

Location

GSK Investigational Site

Monterrey NL, Nuevo León, 64718, Mexico

Location

GSK Investigational Site

Amsterdam, 1081 HV, Netherlands

Location

GSK Investigational Site

Kemerovo, 650002, Russia

Location

GSK Investigational Site

Novosibirsk, 630055, Russia

Location

GSK Investigational Site

Tomsk, 634012, Russia

Location

GSK Investigational Site

Riyadh, Saudi Arabia

Location

GSK Investigational Site

Seoul, 110-744, South Korea

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Seoul, 135-710, South Korea

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Majadahonda (Madrid), 28222, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

GSK Investigational Site

Cambridge, CB23 3RE, United Kingdom

Location

GSK Investigational Site

Clydebank, G81 4DY, United Kingdom

Location

GSK Investigational Site

London, NW3 2QH, United Kingdom

Location

MeSH Terms

Conditions

Hypertension

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2013
• First Posted: June 24, 2013
• Study Start: September 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: March 6, 2017
• Results First Posted: December 16, 2015

Record last verified: 2016-11

Locations

DE (7); AR (4); US (2); ES (4); GB (3); AU (3); CA (2); CN (6); JP (8); KR (3); RU (3); CZ (1); ME (1); SA (1); IL (2); NL (1)