ABS-LT: Study of Ambrisentan in Participants With Pulmonary Hypertension

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00777920
• Collaborator: (none)
• Enrollment: 140
• Locations: 46
• Arm: 1
• Actual Duration (Months): 129.8
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of this study is to monitor the long-term safety of ambrisentan in adult participants with pulmonary hypertension. The available ambrisentan doses for this study are 2.5, 5, or 10 mg administered orally once daily. Investigators will be able to adjust ambrisentan dose as clinically indicated. A minimum of 4 weeks between dose adjustments is required. Participants receiving other therapies for pulmonary hypertension that are not contraindicated for concomitant use with ambrisentan are permitted to enroll in this study and continue to receive such therapies. Participants enrolled in this study will receive treatment with ambrisentan until such time as the investigator or participant chooses to stop ambrisentan treatment, ambrisentan becomes commercially available, or the sponsor stops the study.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Hypertension	Drug: Ambrisentan	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ABS-LT: A Phase 3, Long-Term, Open Label, Multicenter Safety Study of Ambrisentan in Subjects With Pulmonary Hypertension
• Actual Study Start Date: Nov 17, 2008
• Actual Primary Completion Date: Sep 11, 2019
• Actual Study Completion Date: Sep 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ambrisentan Participants will receive ambrisentan 2.5 mg, 5 mg or 10 mg tablet orally once daily until such time as the investigator or participant chooses to stop ambrisentan treatment, ambrisentan becomes commercially available, or the sponsor stops the study.	Drug: Ambrisentan; Tablet administered orally once daily; Other Names: Letairis® Volibris

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Events (AEs) Associated With Long-Term Exposure to Ambrisentan [First dose date of study drug up to the date of last dose plus 30 days (Maximum: approximately 550 weeks)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Men and women with pulmonary hypertension who are discontinuing a clinical study of ambrisentan due to study closure by the sponsor. Eligible participants are those participating in countries where ambrisentan is not yet commercially available. Participants participating in countries where ambrisentan is commercially available may be eligible if they do not qualify for treatment per the current prescribing information of that country.

Key Exclusion Criteria:

• Participants who have discontinued an ambrisentan clinical study for any other reason than sponsor-initiated study closure are not eligible.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Arizona Pulmonary Specialists	Phoenix	Arizona	United States	85013
3	University of Colorado Health Science Center	Aurora	Colorado	United States	80045
4	University of Connecticut Health Center	Farmington	Connecticut	United States	06030
5	Atlanta Institute for Medical Research, Inc.	Atlanta	Georgia	United States	30030
6	University of Iowa	Iowa City	Iowa	United States	52242
7	Tufts Medical Center	Boston	Massachusetts	United States	02111
8	BACH Cardiology/Children's Hospital	Boston	Massachusetts	United States	02115
9	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
10	Boston University Medical Center	Boston	Massachusetts	United States	02118
11	Washington University Medical Center	Saint Louis	Missouri	United States	63110
12	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
13	Mary Parkes Asthma Center University of Rochester	Rochester	New York	United States	14623
14	University of Pittsburgh Medical Center Presbyterian	Pittsburgh	Pennsylvania	United States	15213
15	Rhode Island Hospital	Providence	Rhode Island	United States	02903
16	Lexington Pulmonary and Critical Care Medicine	Lexington	South Carolina	United States	29072
17	Clinica Independencia Munro	Buenos Aires		Argentina	1605
18	Instituto de Investigaciones Clínicas Mar del Plata	Buenos Aires		Argentina	B7600FZN
19	Sanatorio Otamendi y Miroli	Buenos Aires		Argentina	C1115AAb
20	Hospital Británico de Buenos Aires	Buenos Aires		Argentina	C1280AEB
21	UAI Hospital Universitario	Buenos Aires		Argentina	C1437BZL
22	Fundación Rusculleda	Cordoba		Argentina	X5003DCE
23	Instituto de Cardiologia Hospital Italiano de Cordoba	Cordoba		Argentina	X5004FJE
24	Hospital Privado Centro Medico de Cordoba S.A.	Cordoba		Argentina	X5016KEH
25	Instituto de Cardiologia J.F. Cabral	Corrientes		Argentina	W3400AMZ
26	Hospital Italiano	Rosario		Argentina	S2001ODA
27	St. Vincent's Hospital	Darlinghurst	New South Wales	Australia	2010
28	Royal Perth Hospital	Perth	Western Australia	Australia	6000
29	Instituto de Pneumologia e Pediatria Clínica e Pesquisas LTDA ME	Belo Horizonte		Brazil	30380-090
30	UBEA, Hospital Sao Lucas de Pontifícia	Porto Alegre		Brazil	90610 000
31	Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre		Brazil	92020-090
32	Hospital Universitario Clementino Fraga Filho	Rio de Janeiro		Brazil	21949-900
33	Universidade do Estado de Sao Paulo - UNIFESP	Sao Paulo		Brazil	4023-062
34	Hospital das Clinicas da FMUSP	Sao Paulo		Brazil	CEP05403-000
35	Peter Lougheed Centre	Calgary	Alberta	Canada	T1Y 6J4
36	Centro de Estudios Cardiologicos Santiago Oriente	Santiago		Chile	7500503
37	Instituto Nacional del Torax	Santiago		Chile	7500691
38	Hospital Clinico de la Pontificia Universidad Catolica de Chile	Santiago		Chile	8330074
39	Instituto Nacional de Cardiologia Ignacio Chavez	Mexico City		Mexico	14080
40	Unidad de Investigacion Clinica en Medicina S.C.	Monterrey		Mexico	64718
41	State Medico Stomatologic University	Moscow		Russian Federation	109263
42	Russian Cardiology Research Complex	Moscow		Russian Federation	121552
43	Almazov's Federal Heart, Blood & Endocrinology Center	St. Petersburg		Russian Federation	194156
44	Pavlov's State Medical University of St. Petersburg	St. Petersburg		Russian Federation	197022
45	Department of Acute Myocardial Infarction	Kharkov		Ukraine	61039
46	Department of Propedeutics of Internal Medicine No 1	Kiev		Ukraine	3049

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Jun 12, 2013
• Statistical Analysis Plan - Jul 13, 2020

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT00777920
• Other Study ID Numbers: GS-US-300-0124
• First Posted: Oct 22, 2008
• Last Update Posted: Sep 30, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Hypertension, Pulmonary; Hypertension; Ambrisentan

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in Argentina, Australia, Brazil, Canada, Chile, Mexico, Russia, Ukraine, and United States. The first participant was screened on 17 November 2008. The last study observation occurred on 11 September 2019.
Pre-assignment Detail	140 participants were screened.

Arm/Group Title	Ambrisentan
Arm/Group Description	Participants received ambrisentan 2.5 mg, 5 mg or 10 mg tablet orally once daily until such time as the investigator or participant chose to stop ambrisentan treatment, ambrisentan became commercially available, or the sponsor stopped the study.
Period Title: Overall Study
STARTED	140
COMPLETED	90
NOT COMPLETED	50

Baseline Characteristics

Arm/Group Title	Ambrisentan
Arm/Group Description	Participants received ambrisentan 2.5 mg, 5 mg or 10 mg tablet orally once daily until such time as the investigator or participant chose to stop ambrisentan treatment, ambrisentan became commercially available, or the sponsor stopped the study.
Overall Participants	140
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53 (15.9)
Sex: Female, Male (Count of Participants)
Female	110 78.6%
Male	30 21.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	61 43.6%
Not Hispanic or Latino	79 56.4%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 0.7%
Asian	4 2.9%
Black or African American	5 3.6%
White	126 90%
Other	4 2.9%
Region of Enrollment (participants) [Number]
Argentina	18 12.9%
Australia	31 22.1%
Brazil	19 13.6%
Canada	2 1.4%
Chile	13 9.3%
Mexico	12 8.6%
Russia	14 10%
Ukraine	2 1.4%
United States	29 20.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Events (AEs) Associated With Long-Term Exposure to Ambrisentan
Time Frame	First dose date of study drug up to the date of last dose plus 30 days (Maximum: approximately 550 weeks)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included participants who were enrolled into the study and received at least one dose of study drug.

Arm/Group Title	Ambrisentan
Arm/Group Description	Participants received ambrisentan 2.5 mg, 5 mg or 10 mg tablet orally once daily until such time as the investigator or participant chose to stop ambrisentan treatment, ambrisentan became commercially available, or the sponsor stopped the study.
Measure Participants	140
Number [percentage of participants]	90.7 64.8%

Adverse Events

Time Frame	Adverse Events: First dose of study drug up to the date of last dose plus 30 days (Maximum: approximately 550 weeks); All-Cause Mortality: First dose date up to approximately 564 weeks
Adverse Event Reporting Description	The Safety Analysis Set included participants who were enrolled into the study and received at least one dose of study drug.
Arm/Group Title	Ambrisentan
Arm/Group Description	Participants received ambrisentan 2.5 mg, 5 mg or 10 mg tablet orally once daily until such time as the investigator or participant chose to stop ambrisentan treatment, ambrisentan became commercially available, or the sponsor stopped the study.
All Cause Mortality
	Ambrisentan
	Affected / at Risk (%)	# Events
Total	39/140 (27.9%)
Serious Adverse Events
	Ambrisentan
	Affected / at Risk (%)	# Events
Total	80/140 (57.1%)
Blood and lymphatic system disorders
Anaemia	4/140 (2.9%)
Febrile neutropenia	1/140 (0.7%)
Iron deficiency anaemia	1/140 (0.7%)
Neutropenia	1/140 (0.7%)
Pancytopenia	1/140 (0.7%)
Cardiac disorders
Atrial fibrillation	6/140 (4.3%)
Atrial flutter	4/140 (2.9%)
Bradycardia	1/140 (0.7%)
Cardiac arrest	3/140 (2.1%)
Cardiac failure	1/140 (0.7%)
Cardiac failure congestive	5/140 (3.6%)
Cardiogenic shock	2/140 (1.4%)
Cardiopulmonary failure	2/140 (1.4%)
Cor pulmonale	1/140 (0.7%)
Myocardial infarction	2/140 (1.4%)
Palpitations	1/140 (0.7%)
Pericardial effusion	1/140 (0.7%)
Pericarditis	1/140 (0.7%)
Right ventricular dysfunction	1/140 (0.7%)
Right ventricular failure	13/140 (9.3%)
Ear and labyrinth disorders
Deafness unilateral	1/140 (0.7%)
Hypoacusis	1/140 (0.7%)
Gastrointestinal disorders
Ascites	1/140 (0.7%)
Gastrointestinal haemorrhage	1/140 (0.7%)
Gastrooesophageal reflux disease	1/140 (0.7%)
Incarcerated umbilical hernia	1/140 (0.7%)
Inguinal hernia	1/140 (0.7%)
Intestinal ischaemia	1/140 (0.7%)
Intra-abdominal haemorrhage	2/140 (1.4%)
Small intestinal obstruction	1/140 (0.7%)
General disorders
Chest discomfort	1/140 (0.7%)
Chest pain	1/140 (0.7%)
Multiple organ dysfunction syndrome	1/140 (0.7%)
Pyrexia	3/140 (2.1%)
Strangulated hernia	1/140 (0.7%)
Sudden death	1/140 (0.7%)
Hepatobiliary disorders
Cholecystitis	1/140 (0.7%)
Infections and infestations
Abdominal infection	1/140 (0.7%)
Appendicitis	1/140 (0.7%)
Breast cellulitis	1/140 (0.7%)
Cellulitis	1/140 (0.7%)
Dengue fever	1/140 (0.7%)
Device related infection	1/140 (0.7%)
Device related sepsis	1/140 (0.7%)
Infected fistula	1/140 (0.7%)
Infection	1/140 (0.7%)
Infective exacerbation of chronic obstructive airways disease	1/140 (0.7%)
Lower respiratory tract infection	3/140 (2.1%)
Pertussis	1/140 (0.7%)
Pneumonia	12/140 (8.6%)
Respiratory tract infection	2/140 (1.4%)
Salmonellosis	1/140 (0.7%)
Sepsis	4/140 (2.9%)
Streptococcal sepsis	1/140 (0.7%)
Tracheobronchitis	1/140 (0.7%)
Upper respiratory tract infection	1/140 (0.7%)
Urinary tract infection	1/140 (0.7%)
Vascular device infection	2/140 (1.4%)
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis	1/140 (0.7%)
Burns first degree	1/140 (0.7%)
Foot fracture	1/140 (0.7%)
Post procedural haematoma	1/140 (0.7%)
Subdural haematoma	1/140 (0.7%)
Investigations
Alanine aminotransferase increased	2/140 (1.4%)
Aspartate aminotransferase increased	2/140 (1.4%)
International normalised ratio increased	1/140 (0.7%)
Liver function test increased	1/140 (0.7%)
Platelet count decreased	1/140 (0.7%)
Staphylococcus test positive	1/140 (0.7%)
Metabolism and nutrition disorders
Fluid overload	1/140 (0.7%)
Fluid retention	2/140 (1.4%)
Gout	1/140 (0.7%)
Hyperkalaemia	1/140 (0.7%)
Hypokalaemia	1/140 (0.7%)
Hyponatraemia	1/140 (0.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/140 (0.7%)
Haematoma muscle	1/140 (0.7%)
Muscular weakness	1/140 (0.7%)
Osteoarthritis	1/140 (0.7%)
Osteonecrosis	1/140 (0.7%)
Pain in extremity	1/140 (0.7%)
Systemic lupus erythematosus	1/140 (0.7%)
Tenosynovitis	1/140 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/140 (0.7%)
Cervix carcinoma stage III	1/140 (0.7%)
Colon cancer	1/140 (0.7%)
Hepatic cancer	1/140 (0.7%)
Intraductal proliferative breast lesion	1/140 (0.7%)
Neuroendocrine carcinoma	1/140 (0.7%)
Oesophageal carcinoma	1/140 (0.7%)
Rectal adenoma	1/140 (0.7%)
Squamous cell carcinoma	1/140 (0.7%)
Uterine leiomyoma	1/140 (0.7%)
Nervous system disorders
Carotid artery occlusion	1/140 (0.7%)
Cerebrovascular accident	2/140 (1.4%)
Dizziness	1/140 (0.7%)
Headache	1/140 (0.7%)
Sciatica	1/140 (0.7%)
Syncope	3/140 (2.1%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/140 (0.7%)
Product Issues
Device dislocation	1/140 (0.7%)
Device malfunction	1/140 (0.7%)
Renal and urinary disorders
Acute kidney injury	1/140 (0.7%)
Chronic kidney disease	2/140 (1.4%)
Renal impairment	1/140 (0.7%)
Urinary bladder polyp	1/140 (0.7%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/140 (0.7%)
Endometriosis	1/140 (0.7%)
Menorrhagia	1/140 (0.7%)
Metrorrhagia	1/140 (0.7%)
Ovarian cyst	1/140 (0.7%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/140 (1.4%)
Chronic obstructive pulmonary disease	6/140 (4.3%)
Dyspnoea	3/140 (2.1%)
Dyspnoea exertional	1/140 (0.7%)
Epistaxis	1/140 (0.7%)
Haemoptysis	4/140 (2.9%)
Hypoxia	3/140 (2.1%)
Pleural effusion	1/140 (0.7%)
Pneumothorax	1/140 (0.7%)
Pneumothorax spontaneous	1/140 (0.7%)
Productive cough	1/140 (0.7%)
Pulmonary arterial hypertension	5/140 (3.6%)
Pulmonary fibrosis	4/140 (2.9%)
Pulmonary hypertension	12/140 (8.6%)
Respiratory failure	4/140 (2.9%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/140 (0.7%)
Vascular disorders
Aortic stenosis	1/140 (0.7%)
Haematoma	1/140 (0.7%)
Hypotension	3/140 (2.1%)
Peripheral artery occlusion	1/140 (0.7%)
Peripheral artery thrombosis	1/140 (0.7%)
Peripheral ischaemia	2/140 (1.4%)
Venous thrombosis limb	1/140 (0.7%)
Other (Not Including Serious) Adverse Events
	Ambrisentan
	Affected / at Risk (%)	# Events
Total	112/140 (80%)
Blood and lymphatic system disorders
Anaemia	12/140 (8.6%)
Iron deficiency anaemia	11/140 (7.9%)
Cardiac disorders
Atrial fibrillation	9/140 (6.4%)
Palpitations	19/140 (13.6%)
Right ventricular failure	7/140 (5%)
Endocrine disorders
Hypothyroidism	8/140 (5.7%)
Eye disorders
Cataract	7/140 (5%)
Gastrointestinal disorders
Abdominal pain	8/140 (5.7%)
Constipation	9/140 (6.4%)
Diarrhoea	16/140 (11.4%)
Gastrooesophageal reflux disease	13/140 (9.3%)
Nausea	13/140 (9.3%)
Vomiting	9/140 (6.4%)
General disorders
Chest pain	9/140 (6.4%)
Fatigue	16/140 (11.4%)
Oedema peripheral	41/140 (29.3%)
Infections and infestations
Bronchitis	7/140 (5%)
Cellulitis	7/140 (5%)
Lower respiratory tract infection	7/140 (5%)
Pharyngitis	10/140 (7.1%)
Pneumonia	7/140 (5%)
Respiratory tract infection	9/140 (6.4%)
Sinusitis	13/140 (9.3%)
Upper respiratory tract infection	32/140 (22.9%)
Urinary tract infection	12/140 (8.6%)
Investigations
Blood creatinine increased	7/140 (5%)
Gamma-glutamyltransferase increased	10/140 (7.1%)
Heart sounds abnormal	10/140 (7.1%)
International normalised ratio increased	7/140 (5%)
Metabolism and nutrition disorders
Gout	7/140 (5%)
Musculoskeletal and connective tissue disorders
Arthralgia	12/140 (8.6%)
Back pain	9/140 (6.4%)
Pain in extremity	9/140 (6.4%)
Nervous system disorders
Dizziness	19/140 (13.6%)
Headache	25/140 (17.9%)
Syncope	8/140 (5.7%)
Psychiatric disorders
Anxiety	12/140 (8.6%)
Depression	15/140 (10.7%)
Respiratory, thoracic and mediastinal disorders
Cough	15/140 (10.7%)
Dyspnoea	26/140 (18.6%)
Dyspnoea exertional	7/140 (5%)
Epistaxis	8/140 (5.7%)
Nasal congestion	14/140 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years