Efficacy and Safety of Ambrisentan in Children 8-18yrs

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01332331
• Date of registration: 24/03/2011
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: Efficacy and Safety of Ambrisentan in Children 8-18yrs
• Scientific 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
• Date of first enrolment: January 4, 2011
• Target sample size: 41
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01332331
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Argentina, Brazil, Canada, France, Germany, Greece, Hungary, Italy, Japan, Mexico, Netherlands, Russian Federation, Spain, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & 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.



Age minimum: 8 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hypertension, Pulmonary

Intervention(s)

Drug: Ambrisentan - high dose

Drug: Ambrisentan - low dose

Primary Outcome(s)

Number of Participants With Post Baseline PCI Value for Hematology Parameter: Platelet Count [Time Frame: Up to 24 Weeks]

Percentage of Physical Examination Parameter: Saturated Oxygen Level [Time Frame: Week 12 and 24]

Number of Participants With Post Baseline Potential Clinical Importance (PCI) Value for Clinical Chemistry Parameters: Alanine Amino Transferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin and Creatinine [Time Frame: Up to 24 Weeks]

Number of Participants With Abnormal Value for Physical Examination Parameter: Ascites [Time Frame: Week 12 and 24]

Number of Participants With Abnormal Value for Physical Examination Parameter: Jugular Venous Pressure [Time Frame: Week 12 and 24]

Number of Participants With Abnormal Value for Physical Examination Parameter: Liver Size [Time Frame: Week 12 and 24]

Change From Baseline in Plasma Endocrine Parameter - Female : Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at Weeks 12 and 24 [Time Frame: Baseline, Week 12 and 24]

Change From Baseline in Plasma Endocrine Parameter - Female : Sex Hormone Binding Globulin at Weeks 12 and 24 [Time Frame: Baseline, Week 12 and 24]

Number of Participants With Abnormal Value for Physical Examination Parameter: Peripheral Edema [Time Frame: Week 12 and 24]

Number of Participants With Post Baseline PCI Value for Vital Signs Parameter: Heart Rate [Time Frame: Up to 24 Weeks]

Number of Participants With Post Baseline PCI Value for Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Time Frame: Up to 24 Weeks]

Change From Baseline in Plasma Endocrine Parameter - Female : Inhibin B at Weeks 12 and 24 [Time Frame: Baseline, Week 12 and 24]

Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Treatment-emergent Adverse Events (SAEs) [Time Frame: Up to 24 Weeks]

Change From Baseline of Pubertal Development: Men- Testicular Volume (TV) at Weeks 12 and 24 [Time Frame: Baseline, Week 12 and 24]

Number of Participants With Post Baseline PCI Value for Hematology Parameter: Hemoglobin [Time Frame: Up to 24 Weeks]

Number of Participants With Post Baseline PCI Value for Hematology Parameter: Hematocrit [Time Frame: Up to 24 Weeks]

Number of Participants With Post Baseline PCI Value for Vital Signs Parameter: Weight [Time Frame: Up to 24 Weeks]

Secondary Outcome(s)

Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test [Time Frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24]

Time to the First Clinical Worsening of Pulmonary Arterial Hypertension (PAH) [Time Frame: Up to Week 24]

Ratio to Baseline in Plasma N-terminal Pro-B Type Natriuretic Peptide (NT-Pro BNP) Concentration at Week 24 [Time Frame: Baseline, Week 12 and 24]

Change From Baseline in Subject Global Assessment to Week 24 Using the SF-10 Health Survey for Children [Time Frame: Baseline and Week 24]

Change From Baseline in World Health Organization (WHO) Functional Class to Week 24 [Time Frame: Baseline, Week 4, 8, 12, 16, 20 and 24]

Secondary ID(s)

112529

2010-019547-19

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 08/10/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01332331