Last updated: 08/09/2019 12:10:37
Efficacy and Safety of Ambrisentan in children 8-18yrs
EudraCT ID
EU CT Number
Not applicable
Trial status
Terminated (halted prematurely)
Terminated (halted prematurely)
Trial overview
Official title: A randomized, open label study comparing safety and efficacy parameters for a high and a low dose of ambrisentan (adjusted for body weight) for the treatment of pulmonary arterial hypertension in paediatric patients aged 8 years up to 18 years
Trial description: A 6-month (24-week), randomized, open label evaluation of the safety, tolerability, and efficacy of a high and low dose ambrisentan (adjusted for body weight) treatment group in subjects aged 8 years up to 18 years with pulmonary arterial hypertension (PAH). An additional objective is to determine the ambrisentan population pharmacokinetics in the paediatric population. The study will include a screening/baseline period and a treatment period. The treatment period will be 24 weeks or until the subject’s clinical condition deteriorates to the point that alternative/additional treatment is necessary. Patients who participate in the study and in whom continued treatment with ambrisentan is desired will be eligible to enrol into a long term follow-up study. The primary comparison will be the safety and tolerability of the two ambrisentan dose groups (Low vs. High) in the paediatric PAH population The secondary comparison will be the change from baseline for the efficacy parameters between the two treatment groups.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Serious Adverse Events
Timeframe: 24 weeks
Adverse Events
Timeframe: 24 weeks
Clinical Laboratory Parameters
Timeframe: 24 weeks
Physical Examination
Timeframe: 24 weeks
Vital Signs
Timeframe: 24 weeks
Endocrinology assessments
Timeframe: 24 weeks
Hematology
Timeframe: 24 weeks
12 lead ECG
Timeframe: 24 weeks
Secondary outcomes:
Population pharmacokinetic assessment
Timeframe: 24 weeks
Pharmacokinetic/pharmacodynamic modelling
Timeframe: 24 weeks
6 minute walking distance
Timeframe: 24 weeks
Subject Global Assessment
Timeframe: 24 weeks
WHO functional class
Timeframe: 24 weeks
Plasma N-Terminal pro-B-type Natriuretic Peptide (NT-Pro BNP) concentration
Timeframe: 24 weeks
Echocardiogram parameters
Timeframe: 24 weeks
Time to Clinical Worsening
Timeframe: Up to 24 Weeks
Interventions:
Drug: Ambrisentan - low dose
Drug: Ambrisentan - high dose
Enrollment:
41
Observational study model:
Not applicable
Primary completion date:
2013-12-11
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Hypertension, Pulmonary
Product
ambrisentan
Collaborators
Not applicable
Study date(s)
January 2011 to November 2013
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
8 - 18 years
Accepts healthy volunteers
No
- Current diagnosis of PAH (WHO Group 1) with WHO class II or III symptoms in one of the following categories: Idiopathic, Heritable [familial], Secondary to connective tissue disease (e.g., limited scleroderma, diffuse scleroderma, mixed connective tissue disease (CTD), systemic lupus erythematosus, or overlap syndrome), or Persistent PAH despite surgical repair (at least 6 months prior to the screening visit) of atrial septal defects, ventricular septal defects, atrio-ventricular septal defects, and persistent patent ductus.
- Have met the following hemodynamic criteria for subjects with right heart catheterization (RHC) when performed as part of the diagnosis or routine care: mean pulmonary arterial pressure (mPAP) of >/=25 mmHg, pulmonary vascular resistance (PVR) of >/=240 dyne sec/cm5, left ventricular end diastolic pressure (LEVDP) or pulmonary capillary wedge pressure (PCWP) of ≤15 mmHg.
- currently taking an ERA.
- currently taking cyclosporine A.
Inclusion and exclusion criteria
Inclusion criteria:
- Current diagnosis of PAH (WHO Group 1) with WHO class II or III symptoms in one of the following categories: Idiopathic, Heritable [familial], Secondary to connective tissue disease (e.g., limited scleroderma, diffuse scleroderma, mixed connective tissue disease (CTD), systemic lupus erythematosus, or overlap syndrome), or Persistent PAH despite surgical repair (at least 6 months prior to the screening visit) of atrial septal defects, ventricular septal defects, atrio-ventricular septal defects, and persistent patent ductus.
- Have met the following hemodynamic criteria for subjects with right heart catheterization (RHC) when performed as part of the diagnosis or routine care: mean pulmonary arterial pressure (mPAP) of >/=25 mmHg, pulmonary vascular resistance (PVR) of >/=240 dyne sec/cm5, left ventricular end diastolic pressure (LEVDP) or pulmonary capillary wedge pressure (PCWP) of ≤15 mmHg.
- be treatment naïve, have discontinued treatment with another ERA (e.g., bosentan) at least 1 month previously because of elevated liver function tests (LFTs), or have been on a stable dose of drug therapy for PAH (e.g., sildenafil or prostacyclin) for at least one month prior to the Screening Visit.
- Subjects who discontinued ERA treatment due to elevated LFTs, must have LFTs of <3 x Upper Limit of Normal (ULN).
- A female is eligible to participate in this study, as assessed by the investigator, if she is of: a. non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or, b. Child-bearing potential
- has a negative pregnancy test and is not lactating at the Screening and Baseline/Randomisation Visits and, if sexually active, agrees 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 study drug.
- Subject or subject’s legal guardian is able and willing to give written informed consent. As part of the consent, female subjects of childbearing potential will be informed of the risk of teratogenicity and will need to be counselled in a developmentally appropriate manner on the importance of pregnancy prevention; and male subjects will need to be informed of potential risk of testicular tubular atrophy and aspermia.
Exclusion criteria:
- currently taking an ERA.
- currently taking cyclosporine A.
- body weight is less than 20 Kg.
- have not tolerated PAH therapy due to adverse effects which may be related to their mechanism of action (e.g., prostanoids, ERA, PDE-5 inhibitors) with the exception of liver abnormalities for those subjects who were receiving another ERA.
- pregnant or breastfeeding.
- diagnosis of active hepatitis (hepatitis B surface antigen and hepatitis C antibody), or clinically significant hepatic enzyme elevation (i.e., ALT, AST or AP >3xULN) at Screening.
- severe renal impairment (creatinine clearance <30 mL/min) at Screening.
- clinically significant fluid retention in the opinion of the investigator.
- clinically significant anaemia in the opinion of the investigator.
- a known hypersensitivity to the study drug, the metabolites, or formulation excipients.
- have participated in another trial or have taken another investigational product during the previous 30 days.
- alcohol abuse, illicit drug use within 1 year.
- any concurrent condition or concurrent use of medication that would affect subject safety in the opinion of the investigator.
Trial location(s)
Location
GSK Investigational Site
Ann Arbor, Michigan, United States, 48109-4204
Status
Study Complete
Location
GSK Investigational Site
Aurora, Colorado, United States, 80045
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02115
Status
Study Complete
Location
GSK Investigational Site
Ciudad de Buenos Aires, Argentina, 1118
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10032
Status
Study Complete
Location
GSK Investigational Site
San Donato Milanese (MI), Lombardia, Italy, 20097
Status
Study Complete
Study documents
Statistical analysis plan
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Terminated (halted prematurely)
Actual primary completion date
2013-12-11
Actual study completion date
2013-12-11
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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