CLINICAL TRIALS PROFILE FOR AMBRISENTAN

505(b)(2) Clinical Trials for Ambrisentan

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT02688387 ↗	A Phase 1 Relative Bioavailability Study of Ambrisentan and Tadalfil Fixed Dose Combination Tablets in Healthy Subjects	Completed	Covance Harrogate	Phase 1	2016-03-18	This study is designed to understand the relative bioavailability (proportion of the administered dose that is absorbed into the bloodstream) of several fixed dose combinations (FDCs) tablets of ambrisentan and tadalafil for further development and to provide pharmacokinetic (PK - what the body does to the drug) data to enable a pivotal bioequivalence (BE - the relationship between two preparations of the same drug in the same dosage form that have a similar bioavailability) study. Depending on formulation work, the study will allow up to 8 new FDCs to be compared with the reference of ambrisentan and tadalafil monotherapies. The study will also evaluate up to 2 of the new formulations, that may be taken in to a BE study, to be tested for any effect on pharmacokinetics of the FDC in both fed and fasted state. This is a single centre, Phase 1, single dose, randomised, open label crossover study with 3 study parts; each study part will have up to a 5 way crossover in healthy subjects. Part 1 of the study will evaluate four formulations of the FDC (ambrisentan 10 milligram [mg] + tadalafil 40 mg) and the reference of the 2 monotherapy components taken concurrently (ambrisentan 10 mg and tadalafil 40 mg) in the fasted stated. If successful formulations are identified in this part of the study, then they will be re-formulated and tested in part 2. If no successful formulations are identified in part 1 of the study, then part 2 will be utilized to look at up to 4 new FDC formulations. However, if only two formulations, or less, are evaluated in part 2 then the FDC formulations may be tested both fed and fasted to assess food effect and part 3 will not be required. If successful formulations are identified in this study part, then up to 2 of these may be tested, for food effect, in Part 3 if not already assessed in this part. Therefore, part 3 is optional and utility is dependent on the results of the previous study parts.
New Formulation	NCT02688387 ↗	A Phase 1 Relative Bioavailability Study of Ambrisentan and Tadalfil Fixed Dose Combination Tablets in Healthy Subjects	Completed	Hammersmith Medicines Research	Phase 1	2016-03-18	This study is designed to understand the relative bioavailability (proportion of the administered dose that is absorbed into the bloodstream) of several fixed dose combinations (FDCs) tablets of ambrisentan and tadalafil for further development and to provide pharmacokinetic (PK - what the body does to the drug) data to enable a pivotal bioequivalence (BE - the relationship between two preparations of the same drug in the same dosage form that have a similar bioavailability) study. Depending on formulation work, the study will allow up to 8 new FDCs to be compared with the reference of ambrisentan and tadalafil monotherapies. The study will also evaluate up to 2 of the new formulations, that may be taken in to a BE study, to be tested for any effect on pharmacokinetics of the FDC in both fed and fasted state. This is a single centre, Phase 1, single dose, randomised, open label crossover study with 3 study parts; each study part will have up to a 5 way crossover in healthy subjects. Part 1 of the study will evaluate four formulations of the FDC (ambrisentan 10 milligram [mg] + tadalafil 40 mg) and the reference of the 2 monotherapy components taken concurrently (ambrisentan 10 mg and tadalafil 40 mg) in the fasted stated. If successful formulations are identified in this part of the study, then they will be re-formulated and tested in part 2. If no successful formulations are identified in part 1 of the study, then part 2 will be utilized to look at up to 4 new FDC formulations. However, if only two formulations, or less, are evaluated in part 2 then the FDC formulations may be tested both fed and fasted to assess food effect and part 3 will not be required. If successful formulations are identified in this study part, then up to 2 of these may be tested, for food effect, in Part 3 if not already assessed in this part. Therefore, part 3 is optional and utility is dependent on the results of the previous study parts.
New Formulation	NCT02688387 ↗	A Phase 1 Relative Bioavailability Study of Ambrisentan and Tadalfil Fixed Dose Combination Tablets in Healthy Subjects	Completed	GlaxoSmithKline	Phase 1	2016-03-18	This study is designed to understand the relative bioavailability (proportion of the administered dose that is absorbed into the bloodstream) of several fixed dose combinations (FDCs) tablets of ambrisentan and tadalafil for further development and to provide pharmacokinetic (PK - what the body does to the drug) data to enable a pivotal bioequivalence (BE - the relationship between two preparations of the same drug in the same dosage form that have a similar bioavailability) study. Depending on formulation work, the study will allow up to 8 new FDCs to be compared with the reference of ambrisentan and tadalafil monotherapies. The study will also evaluate up to 2 of the new formulations, that may be taken in to a BE study, to be tested for any effect on pharmacokinetics of the FDC in both fed and fasted state. This is a single centre, Phase 1, single dose, randomised, open label crossover study with 3 study parts; each study part will have up to a 5 way crossover in healthy subjects. Part 1 of the study will evaluate four formulations of the FDC (ambrisentan 10 milligram [mg] + tadalafil 40 mg) and the reference of the 2 monotherapy components taken concurrently (ambrisentan 10 mg and tadalafil 40 mg) in the fasted stated. If successful formulations are identified in this part of the study, then they will be re-formulated and tested in part 2. If no successful formulations are identified in part 1 of the study, then part 2 will be utilized to look at up to 4 new FDC formulations. However, if only two formulations, or less, are evaluated in part 2 then the FDC formulations may be tested both fed and fasted to assess food effect and part 3 will not be required. If successful formulations are identified in this study part, then up to 2 of these may be tested, for food effect, in Part 3 if not already assessed in this part. Therefore, part 3 is optional and utility is dependent on the results of the previous study parts.

All Clinical Trials for Ambrisentan

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00091598 ↗	ARIES - Ambrisentan in Patients With Moderate to Severe Pulmonary Arterial Hypertension (PAH)	Completed	Gilead Sciences	Phase 3	2004-01-01	The primary objective is to determine the effect of ambrisentan on exercise capacity in subjects with PAH.
NCT00380068 ↗	Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension	Completed	Gilead Sciences	Phase 3	2006-08-01	The primary objective of this study was to evaluate the safety and efficacy of ambrisentan in a broad population of participants with pulmonary hypertension (PH). Secondary objectives of this study were to evaluate the effects of ambrisentan on other clinical measures of pulmonary arterial hypertension (PAH), long-term treatment success, and survival.
NCT00423202 ↗	A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess Safety and Efficacy of Ambrisentan in Subjects With Pulmonary Arterial Hypertension.	Completed	Gilead Sciences	Phase 3	2003-12-01	A phase 3, randomized, double-blind, placebo-controlled study to assess safety and efficacy of ambrisentan in subjects with pulmonary arterial hypertension.
NCT00423592 ↗	Phase 2 Study of Ambrisentan for Liver Function Test Rescue in Pulmonary Arterial Hypertension	Completed	Gilead Sciences	Phase 2	2005-05-01	This Phase 2 study was to determine the incidence of increased serum aminotransferase concentrations (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]), as well as the overall safety and tolerability of ambrisentan, in participants with pulmonary arterial hypertension (PAH), idiopathic PAH (IPAH), or familial PAH (FPAH) who had previously discontinued ERA therapy (bosentan or sitaxsentan) due to increased serum ALT or AST concentrations.
NCT00423748 ↗	Study to Assess Safety and Efficacy of Ambrisentan in Subjects With Pulmonary Arterial Hypertension.	Completed	Gilead Sciences	Phase 3	2003-12-01	A phase 3, randomized, double-blind, placebo-controlled study to assess safety and efficacy of ambrisentan in subjects with pulmonary arterial hypertension.
NCT00424021 ↗	Phase 2 Extension Study of Ambrisentan in Pulmonary Arterial Hypertension	Completed	Gilead Sciences	Phase 2	2003-04-01	AMB-220-E is an international, multicenter, open-label study examining the long-term safety of ambrisentan (BSF 208075) in subjects who have previously completed Myogen study NCT00046319, "A Phase II, Randomized, Double-Blind, Dose-Controlled, Dose-Ranging, Multicenter Study of BSF 208075 Evaluating Exercise Capacity in Subjects with Moderate to Severe Pulmonary Arterial Hypertension".
NCT00424034 ↗	A Study of GSK1325760A in Healthy Japanese Subjects	Completed	GlaxoSmithKline	Phase 1	2007-01-01	To investigate the safety, tolerability, pharmacokinetics and the effect of food on pharmacokinetics after single oral administrations of GSK1325760A

Clinical Trial Conditions for Ambrisentan

Condition Name

Condition Name for Ambrisentan
Intervention	Trials
Pulmonary Arterial Hypertension	17
Pulmonary Hypertension	15
Hypertension, Pulmonary	8
Systemic Sclerosis	5

Condition MeSH

Condition MeSH for Ambrisentan
Intervention	Trials
Hypertension	45
Pulmonary Arterial Hypertension	30
Hypertension, Pulmonary	29
Familial Primary Pulmonary Hypertension	28

Clinical Trial Locations for Ambrisentan

Trials by Country

Trials by Country for Ambrisentan
Location	Trials
United States	229
Germany	42
Canada	34
Spain	23
Australia	22

Trials by US State

Trials by US State for Ambrisentan
Location	Trials
Massachusetts	14
California	13
Texas	11
North Carolina	11
Pennsylvania	10

Clinical Trial Progress for Ambrisentan

Clinical Trial Phase

Clinical Trial Phase for Ambrisentan
Clinical Trial Phase	Trials
Phase 4	11
Phase 3	16
Phase 2/Phase 3	3

Clinical Trial Status

Clinical Trial Status for Ambrisentan
Clinical Trial Phase	Trials
Completed	39
Terminated	11
Recruiting	5

Clinical Trial Sponsors for Ambrisentan

Sponsor Name

Sponsor Name for Ambrisentan
Sponsor	Trials
Gilead Sciences	22
GlaxoSmithKline	13
United Therapeutics	3

Sponsor Type

Sponsor Type for Ambrisentan
Sponsor	Trials
Other	97
Industry	47
NIH	4

Ambrisentan: Clinical Trials, Market Analysis, and Projections

Introduction to Ambrisentan

Ambrisentan is a propanoic acid-based, A-selective endothelin receptor antagonist used for the once-daily treatment of pulmonary arterial hypertension (PAH). It works by blocking the endothelin-1 receptor, a potent vasoconstrictor, leading to the relaxation and dilation of blood vessels in the pulmonary arteries, thereby improving exercise capacity and quality of life for patients with PAH[4,.

Clinical Trials Overview

ARIES-1 and ARIES-2 Studies

The ARIES-1 and ARIES-2 studies were concurrent, double-blind, placebo-controlled trials that evaluated the efficacy and safety of ambrisentan in patients with PAH. These studies randomized 202 and 192 patients, respectively, to receive either placebo or ambrisentan (5 mg or 10 mg in ARIES-1, and 2.5 mg or 5 mg in ARIES-2) once daily for 12 weeks. The primary endpoint was the change in 6-minute walk distance (6MWD) from baseline to week 12.

Key findings from these studies include:

• Significant improvements in 6MWD, with mean placebo-corrected treatment effects ranging from 31 meters to 59 meters across different doses.
• Improvements in secondary endpoints such as time to clinical worsening, World Health Organization (WHO) functional class, Short Form-36 Health Survey score, Borg dyspnea score, and B-type natriuretic peptide plasma concentrations.
• Low risk of aminotransferase abnormalities, with no patient developing concentrations greater than three times the upper limit of normal[1].

ARIES-3 Study

The ARIES-3 study was an open-label, single-arm, multicenter Phase III trial designed to evaluate the efficacy and safety of ambrisentan in a broader PH population. This study enrolled 224 patients and showed a mean improvement in 6MWD of 21 meters from baseline at 24 weeks. The study also reported a high probability of no clinical worsening and low incidence of severe aminotransferase elevations[5].

Post-Marketing Surveillance in Korea

A post-marketing surveillance (PMS) study conducted in Korea from 2015 to 2021 evaluated the safety and effectiveness of ambrisentan in real-world practice. The study involved 293 patients and found that ambrisentan was well-tolerated, with an overall incidence of adverse events (AEs) at 52.22% and adverse drug reactions (ADRs) at 10.92%. The study also noted significant improvements in WHO functional class and patient-reported symptoms, with 87.15% of subjects reporting symptom improvement after treatment[2].

Market Analysis

Current Market Trends

The ambrisentan market is experiencing significant growth driven by several factors:

• Increasing Prevalence of PAH: The rising number of patients diagnosed with PAH is a major driver of the market.
• Investments in Research and Development: Continuous innovations in drug delivery systems and combination therapies are enhancing patient compliance and treatment outcomes[4].
• Global Awareness and Healthcare Expenditures: Growing awareness of PAH and increasing healthcare expenditures are contributing to the market's expansion.

Market Projections

The global ambrisentan market is projected to grow at a compound annual growth rate (CAGR) of 5-7% through 2028. This growth is expected to be fueled by the increasing prevalence of PAH, innovative treatments, and robust investment in research and development. The market value is estimated to reach several billion dollars in the coming years, driven by the drug's efficacy and demand[4].

Key Players

The main players in the ambrisentan market include:

• Gilead Sciences: The primary developer and marketer of ambrisentan.
• GSK: A significant player in the pharmaceutical industry with interests in PAH treatments.
• Hansoh Pharma: Another major pharmaceutical company involved in the market[3].

Safety and Effectiveness

Safety Profile

Ambrisentan has been shown to be well-tolerated in clinical trials and real-world studies. Key safety findings include:

• Low Risk of Aminotransferase Abnormalities: Unlike some other endothelin receptor antagonists, ambrisentan is associated with a low risk of liver enzyme elevations[1][5].
• Common Adverse Events: Peripheral edema, headache, dyspnea, upper respiratory tract infection, nasal congestion, fatigue, and nausea are among the most frequent adverse events reported[5].

Effectiveness

The drug has demonstrated significant effectiveness in improving exercise capacity, delaying clinical worsening, and enhancing quality of life for PAH patients. Improvements in 6MWD, WHO functional class, and patient-reported symptoms are consistent across various studies[1][2][5].

Innovations and Future Directions

Advancements in Drug Delivery

Recent innovations include extended-release formulations and combination therapies that aim to enhance patient compliance and treatment outcomes. These advancements are crucial in transforming pulmonary health outcomes worldwide[4].

Combination Therapies

Combination therapies involving ambrisentan and other PAH treatments, such as sildenafil and prostanoids, are being explored to optimize treatment regimens and improve patient outcomes[5].

Market Opportunities and Challenges

Investment Opportunities

The ambrisentan market presents significant investment opportunities due to its growing demand, innovative treatments, and robust investment landscape. Pharmaceutical companies are keen to explore this lucrative market, driven by increasing healthcare expenditures and the need for effective PAH treatments[4].

Challenges

Despite the promising growth, the market faces challenges such as the need for continuous monitoring due to potential side effects like liver function abnormalities and anemia. Additionally, the impact of concomitant medications and age on adverse event incidence must be carefully managed[2][4].

Key Takeaways

• Clinical Efficacy: Ambrisentan has been shown to improve exercise capacity, delay clinical worsening, and enhance quality of life in PAH patients.
• Safety Profile: The drug is well-tolerated with a low risk of aminotransferase abnormalities.
• Market Growth: The global ambrisentan market is projected to grow at a CAGR of 5-7% through 2028.
• Innovations: Advancements in drug delivery systems and combination therapies are transforming treatment outcomes.
• Investment Opportunities: The market offers significant investment opportunities driven by increasing demand and innovative treatments.

FAQs

Q: What is ambrisentan used for?

A: Ambrisentan is used to treat pulmonary arterial hypertension (PAH) by dilating blood vessels in the lungs, improving exercise capacity, and enhancing quality of life[4].

Q: What are the common adverse events associated with ambrisentan?

A: Common adverse events include peripheral edema, headache, dyspnea, upper respiratory tract infection, nasal congestion, fatigue, and nausea[5].

Q: How does ambrisentan compare to other endothelin receptor antagonists in terms of liver safety?

A: Ambrisentan is associated with a low risk of aminotransferase abnormalities, unlike some other endothelin receptor antagonists[1][5].

Q: What are the key drivers of the ambrisentan market growth?

A: The market growth is driven by the increasing prevalence of PAH, investments in research and development, and growing global awareness of PAH[4].

Q: Who are the main players in the ambrisentan market?

A: The main players include Gilead Sciences, GSK, and Hansoh Pharma[3].

Sources

1. Galie, N., et al. "Ambrisentan for the treatment of pulmonary arterial hypertension." American Journal of Respiratory and Critical Care Medicine, vol. 177, no. 11, 2008, pp. 1128-1135. DOI: 10.1164/rccm.200712-1912OC[1].
2. Kim, H., et al. "Results from the Korean post-marketing surveillance." Journal of Clinical Pharmacology, vol. 63, no. 10, 2023, pp. 1341-1351. DOI: 10.1002/jcph.2059[2].
3. Valuates Reports. "Global and United States Ambrisentan Drug Market Research Report 2024." Valuates Reports, 2024[3].
4. Market Research Intellect. "Ambrisentan in Focus: Market Trends and Innovations Transforming Pulmonary Health." Market Research Intellect, 2024[4].
5. Gilead Sciences. "New Data for Gilead Sciences' Ambrisentan Show Clinical Improvements in a Diverse Pulmonary Hypertension Population." Gilead Sciences, 2009[5].