Efficacy Study of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension (PAH)

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01808313
• Date of registration: 28/02/2013
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: Efficacy Study of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension (PAH)
• Scientific title: An Open Label Phase IIIb Study to Evaluate Efficacy and Safety of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension (PAH)
• Date of first enrolment: December 1, 2012
• Target sample size: 134
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01808313
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

China

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Signed written informed consent prior to beginning study-related procedures.

- Subject must be between 18-75 years of age, inclusive, at the Screening Visit.

- Subjects must weight =40 kg at the Screening Visit.

- Subjects must have symptomatic or severe PAH (WHO functional class II or III) and be
categorised as class 1 PAH (defined by the Updated Clinical Classification of
Pulmonary Hypertension 2009), due to iPAH, congenital heart disease-congenital heart
defects repaired greater than 1 year prior to screening (i.e., atrial septal defects,
ventricular septal defects or patent ductus arteriosus) or CTD-related PAH (e.g.,
limited scleroderma, diffuse scleroderma, mixed CTD, systemic lupus erythematosus or
overlap syndrome).

NOTE: subjects with portopulmonary hypertension and pulmonary venoocclusive disease are NOT
eligible for the study.

- Subjects must have had a right heart catheterisation within 6 months prior to
screening and meet all of the following haemodynamic criteria:

1. Mean PAP = 25 mmHg.

2. A PVR = 240 dyn/sec/cm5.

3. A PCWP or left ventricular (LV) end-diastolic pressure of = 15 mmHg.

- Subjects must be able to walk a distance of at least 150 m but no more than 450 m. In
addition, the screening and baseline 6MWT test values must not vary by greater than
10% (calculated using (baseline - screening)/screening with the result to be between
-0.1 and 0.1).

- Subjects must meet both of the following pulmonary function criteria. The tests should
have been completed no more than 24 weeks prior to the Screening Visit, if not
performed within the previous 24 weeks, the test must be completed at Day 0:

1. Total lung capacity (TLC) = 60% of predicted normal.

2. Forced expiratory volume in one second (FEV1) = 55% of predicted normal.

- Subjects receiving CCBs must be on stable therapy (i.e., the dose level does not need
to change to maintain disease control) for at least 1 month prior to the Screening
Visit.

- Subjects receiving 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
inhibitors (i.e., statins) must be on stable therapy (i.e., the dose level does not
need to change to maintain disease control) for at least 12 weeks prior to the
Screening Visit.

- Female subjects of childbearing potential must have a negative pregnancy test at the
Screening Visit and Day 0.

- Female subjects of childbearing potential who are sexually active must agree to use
two reliable methods of contraception (as described in Appendix 3 ) from the Screening
Visit until study completion and for at least 30 days following the last dose of IP.
Subjects who have had a Copper T 380A intrauterine device (IUD) or LNg 20 IUD inserted
are not required to use an additional method of contraception.

- Subject must agree not to participate in a clinical study involving another IP or
device throughout this study.

Exclusion Criteria:

- The subject has received PAH therapy (PDE-5 inhibitors, ERA, chronic prostanoid*)
within 4 weeks prior to the Screening Visit.

*Prostanoid use is classed as chronic when treatment continues for more than 7 days.

- The subject has received intravenous inotropes (e.g., dopamine, dobutamine) within 2
weeks prior to the Screening Visit.

- The subject has previously been discontinued from ERA treatment (e.g., bosentan) due
to safety or tolerance issues other than those associated with liver function
abnormalities.

- The subject has a serum alanine aminotransferase (ALT) or aspartate aminotransferase
(AST) value that is >2 x the upper limit of normal (ULN) at the Screening Visit.

- The subject has serum bilirubin value that is >1.5 x ULN at the Screening Visit.

- The subject has severe hepatic impairment (Child-Pugh class C with or without
cirrhosis) at the Screening Visit.

- The subject has severe renal impairment (creatinine clearance <30 mL/min) at the
Screening Visit.

- The subject has clinically significant anaemia, defined as haemoglobin concentration
<10 g/dL or haematocrit <30% at the Screening Visit.

- The subject has a laboratory result, physical examination finding, medical history
incident or other finding, which is a contraindication for treatment with an ERA.
Contraindications for treatment include, but are not limited to, evidence of elevated
liver functions test or previously experiencing an event that would be defined as a
serious AE (SAE) in a clinical trial (see Section 6.3.3.2), which was attributed to
treatment with an ERA.

- The subject has severe hypotension (either diastolic blood pressure <50 mmHg or
systolic blood pressure <90 mmHg).

- The subject has, in the opinion of the Investigator, clinically significant aortic or
mitral valve disease, pericardial constriction, restrictive or congestive
cardiomyopathy, life-threatening cardiac arrhythmias, significant LV dysfunction
(defined as LV ejection fraction <45%), LV outflow obstruction, symptomatic coronary
artery disease, autonomic hypotension or fluid depletion.

- The subject has a history of malignancies within the past 5 years, with the exception
of basal cell carcinoma of the skin or in situ carcinoma of the cervix.

- The subject has cardiovascular, liver, renal, haematological, gastrointestinal,
immunological, endocrine, metabolic or central nervous system disease that, in the
opinion of the Investigator, may adversely affect the safety of the subject and/or
efficacy of the study drug or severely limit the lifespan of the subject.

- A female subject who is pregnant or breastfeeding.

- The subject has demonstrated non-compliance with previous medical regimens or is
unable to comply with the procedures described in this protocol.

- The subject has a history of abusing alcohol or drugs of abuse (including
amphetamines, methamphetamines, opiates, cannabinoids, cocaine, benzodiazepines or
barbiturates) within 12 months prior to the Screening Visit. Use of such drugs if
prescribed by a Doctor and used according to the prescription would not exclude a
subject.

- The subject has participated in a clinical study involving another IP or device within
4 weeks or five half-lives of an IP, whichever is longer, before the Screening Visit.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Vascular Disease

Intervention(s)

Drug: ambrisentan

Primary Outcome(s)

Change From Baseline in 6-minutes Walk Test (6MWT) at Week 12 [Time Frame: Baseline and Week 12]

Secondary Outcome(s)

Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24 [Time Frame: Baseline, Week 12 and Week 24]

Change From Baseline in Systolic and Diastolic Blood Pressure at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Mean Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Change From Baseline in Albumin, Globulin and Total Protein at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Number of Participants With Physical Examination Findings [Time Frame: Baseline, Week 12 and Week 24]

Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event [Time Frame: Baseline up to Week 24]

Change From Baseline in 6MWT at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Electrocardiogram (ECG) Heart Rate Values at Weeks 12 and 24 [Time Frame: Baseline, Week 12 and Week 24]

Change From Baseline in Heart Rate at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Number of Participants With Shift From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) and Total Bilirubin (BILT) up to Week 24 [Time Frame: Baseline up to Week 24]

Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Weeks 12 and 24 [Time Frame: Baseline, Week 12 and Week 24]

Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 [Time Frame: Baseline, Week 12 and Week 24]

Oral Temperature [Time Frame: Baseline]

Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, Potassium, Magnesium, Sodium, Inorganic Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Change From Baseline in Hematocrit at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Interval Corrected Bazett's Formula (QTcB) Values at Weeks 12 and 24 [Time Frame: Baseline, Week 12 and Week 24]

Number of Participants With Urinalysis Data at Baseline and Week 24 [Time Frame: Baseline and Week 24]

Number of Participants With Any Adverse Events, Any Serious Adverse Events and Adverse Events Leading to Discontinuation [Time Frame: From the start of study treatment up to Week 24]

Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at the Indicated Time Points up to Week 24 [Time Frame: Baseline up to Week 24]

Secondary ID(s)

115812

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 12/05/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01808313