Phase 2 N=38 Treatment

Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529

Hypertension, Pulmonary

Bottom Line

View on ClinicalTrials.gov: NCT01342952 ↗

Enrolled (actual)

Serious AEs

55.3%

Results posted

Dec 2022

Primary outcome: Primary: Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) — 3; 13; 5; 10 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Ambrisentan (Drug)
Age: Pediatric, Adult · 8+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: Jun 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs)	3; 13; 5; 10; 2; 7	—
PRIMARY Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin	-7.5; -1.0; 0.8; 4.0; -11.8; -5.6	—
PRIMARY Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN)	-0.150; -0.054; 0.028; -0.060; 1.7; 2.6	—
PRIMARY Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH)	-77.7; -109.5; -148.8; -135.6; -18.7; 4.0	—
PRIMARY Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid	6.27; 8.16; 10.26; 19.31; -64.67; -83.60	—
PRIMARY Change From Baseline in Chemistry Parameters: Albumin, Total Protein	-3.3; -1.2; 1.6; -2.0; -3.7; -3.4	—
PRIMARY Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC)	-23.0; -4.7; 0.8; 1.3; -9.3; -12.4	—
PRIMARY Change From Baseline in Hematology Parameters: Hematocrit	-0.0610; -0.0004; 0.0100; 0.0040	—
PRIMARY Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count	-0.007; 0.019; -0.006; -0.002; -0.210; 0.034	—
PRIMARY Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin	-1.70; -1.46; -0.70; 0.11	—
PRIMARY Change From Baseline in Hematology Parameter: Mean Corpuscle Volume	-2.3; -1.0; -0.8; 0.8	—
PRIMARY Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes	-0.57; 0.07; 0.14; 0.00; 0.01427; -0.00816	—
PRIMARY Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites	0; 0; 0; 0; 0; 0	—
PRIMARY Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema	0; 0; 0; 0; 0; 0	—
PRIMARY Percentage of Saturated Oxygen Level (Physical Examination Parameter)	95.5; 96.8; 97.4; 96.9	—
PRIMARY Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	16.3; 8.4; 1.2; 8.5; 1.5; 2.3	—
PRIMARY Change From Baseline in Vital Signs Parameter: Heart Rate	-9.0; -4.0; -3.8; -6.0	—
PRIMARY Change From Baseline in Vital Signs Parameter: Weight	17.43; 10.73; 7.12; 12.17	—
PRIMARY Change From Baseline in Vital Sign Parameter: Height	25.3; 9.9; 7.2; 12.1	—
PRIMARY Change From Baseline in Vital Sign Parameter: Body Mass Index	2.65; 2.45; 1.52; 1.99	—
PRIMARY Change From Baseline in Vital Sign Parameter: Body Surface Area	0.398; 0.207; 0.144; 0.236	—
PRIMARY Number of Participants With Abnormal Electrocardiogram (ECG) Findings	4; 14; 3; 9; 0; 2	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study	0.200; 3.217; 0.100; -0.336; 0.03; 5.17	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants	35.800; 0.800; -2.500; 0.967; 8.60; 6.17	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at End of Study	0.0; 14.0; -29.0	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at 20 Years of Age of Participants	0.0; 49.0; 37.0; 7.5	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at End of Study	-10.0; 11.8; 0.5; 17.3	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at 20 Years of Age of Participants	49.0; 1.7; 10.0; -15.5	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at End of Study	0.00; -6.80; -26.00; 17.00	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at 20 Years of Age of Participants	-7.00; 179.00; 11.00; 89.00	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Estriol at End of Study	—	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Estriol at 20 Years of Age of Participants	—	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at End of Study	-11.00; -77.25; -255.50; 44.80	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at 20 Years of Age of Participants	55.50; -107.00; 15.00; 387.50	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study	6.000; 0.267; 3.250; 0.850; 3.20; 1.70	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at 20 Years of Age of Participants	2.350; 0.500; 2.90; 0.60	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at End of Study	15.0; 8.5; 73.0	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at 20 Years of Age of Participants	23.0; -47.0	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at End of Study	-28.5; -11.5; -11.0	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at 20 Years of Age of Participants	-2.5; 12.0	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at End of Study	10.650; 2.900; 7.300; 17.175	—
PRIMARY Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at 20 Years of Age of Participants	4.000; 6.600	—
PRIMARY Change From Baseline of Pubertal Development in Male: Testicular Volume at End of Study	0.0; 15.0; 11.5; 6.0; 16.5; 13.0	—
PRIMARY Change From Baseline of Pubertal Development in Male: Testicular Volume at 20 Years of Age of Participants	15.0; 8.0; 17.0; 16.5; 8.0	—
PRIMARY Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, Phosphodiesterase Type 5 [PDE-5] Inhibitors) Due to Tolerability Issues	393.0; 468.5; 354.0; 1448.7	—
SECONDARY Number of Participants With All-cause Death	0; 4; 1; 2	—
SECONDARY Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test	98.53; 56.74; 3.05; 34.24; -13.05; 130.41	—
SECONDARY Time to the First Clinical Worsening of PAH	315.5; 896.2; 1122.0; 228.0	—
SECONDARY Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Deterioration of Clinical Condition	510.0; 697.5; 909.0; 345.5	—
SECONDARY Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Lack of Beneficial Effect With Previous Therapy	315.5; 173.0	—
SECONDARY Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, PDE-5 Inhibitors) Due to Deterioration of Clinical Condition	1247.3; 1097.0; 909.0; 345.5	—
SECONDARY Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children	-1.618; -0.967; -1.788; -0.272; -0.336; -1.880	—
SECONDARY Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH	5; 5; 3; 0; 4; 6	—
SECONDARY Percentage Change From Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) Concentration	-62.59; -56.02; 59.06; 101.96	—

Summary

An open label, long term extension to Study AMB112529. All subjects may remain in the extension study for a minimum of six months. Beyond the six month period, subjects may continue in the extension study until one of the following conditions is met: the subject turns 18 years of age (when the subject can receive marketed product) the product is approved and available for use in the subject's age group, development for use in the paediatric population is discontinued. the subject decides he/she no longer wants to participate in the study, the investigator considers it is in the best interest of the subject to discontinue ambrisentan (e.g. for safety reasons). The primary objective is the long-term safety and tolerability of ambrisentan in the paediatric PAH population. Secondary objectives are all cause mortality and change from baseline in Study AMB112529 on efficacy parameters.

Eligibility Criteria

Inclusion Criteria

Have participated in and complied, to the best of their ability, with the protocol for AMB112529 and have met one of the following:
Completed the Week 24 visit in AMB112529;
Required additional targeted treatment for PAH due to inadequate response to the current treatment or worsening of their clinical condition prior to week 24 in AMB112529;
Required reduction in dose of baseline targeted treatment for PAH after ambrisentan was added to the treatment regimen;
In the opinion of the investigator, continued treatment with ambrisentan is warranted.
A female is eligible to participate in this study, as assessed by the investigator, if she is of:
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or,
Child-bearing potential - has a negative pregnancy test and is not lactating and, if sexually active, agrees to continue to use 2 reliable methods of contraception until study completion and for at least 30 days following the last dose of study drug (reliable methods of contraception are listed in Appendix 2).
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

Subjects who were withdrawn from ambrisentan in Study AMB112529;
Subjects who did not comply with the protocol in Study AMB112529;
Female subjects who are pregnant or breastfeeding;
Subjects with severe renal impairment (estimated creatinine clearance <30 mL/min assessed within the previous 45 days) at the point of transition from Study AMB112529 into this study;
Subject with clinically significant fluid retention in the opinion of the investigator;
Subject with clinically significant anaemia in the opinion of the investigator;
Subjects who are to enter another clinical trial or be treated with another investigational product after exiting Study AMB112529.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01342952). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.