Phase 2 Study of Ambrisentan for Liver Function Test Rescue in Pulmonary Arterial Hypertension

NCT00423592 | Completed Phase 2 Results

• 1 other identifier: AMB-222
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• The Incidence of Confirmed Serum Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) Concentrations > 3 x the Upper Limit of Normal (ULN) Considered to be Related to Ambrisentan and Resulted in Discontinuation of Study Drug.

  The number of participants in the safety analysis set with confirmed serum ALT or AST concentrations \> 3 x ULN during 12 weeks of ambrisentan therapy that were related to ambrisentan and resulted in discontinuation of study drug. Safety analysis set included all participants who received at least 1 dose of study drug.

  Week 12

Secondary Outcomes (15)

• The Incidence of Confirmed Serum ALT or AST Concentrations > 5 x ULN That Were Related to Ambrisentan and Resulted in Discontinuation of Study Drug.

  Week 12

• The Incidence of Confirmed Serum ALT or AST Concentrations > 3 x ULN That Were Related to Ambrisentan and Resulted in Dose Reduction

  Week 12

• A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in the 6-Minute Walk Distance Test (6MWD)

  Baseline to Week 12

• A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Borg Dyspnea Index Immediately Following Exercise

  Baseline to Week 12

• A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in WHO Functional Class

  Baseline to Week 12

Interventions

ambrisentan DRUG

All eligible subjects received 2.5 mg ambrisentan once daily for a period of 4 weeks before increasing the dose to 5 mg once daily. After Week 24, investigators were allowed to adjust the dose of ambrisentan as clinically indicated (available doses were 2.5, 5, and 10 mg).

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and Females between 12 and 75 years of age
• Current diagnosis of IPAH, FPAH, or PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts, anorexigen use, HIV infection
• Must have previously discontinued bosentan or sitaxsentan therapy due to serum aminotransferase (ALT and/or AST) concentrations \> 3 x ULN
• Must have normal (\< 1 x ULN) serum ALT and AST concentrations at screening
• Six-minute Walk distance of at least 150 meters at screening
• If receiving sildenafil or a clinically approved prostanoid for PAH, must have been on stable therapy for at least 4 weeks prior to screening
• Subjects with a diagnosis of HIV must have stable disease status during the screening period

Sponsors & Collaborators

• Gilead Sciences: lead

Related Publications (1)

• McGoon MD, Frost AE, Oudiz RJ, Badesch DB, Galie N, Olschewski H, McLaughlin VV, Gerber MJ, Dufton C, Despain DJ, Rubin LJ. Ambrisentan therapy in patients with pulmonary arterial hypertension who discontinued bosentan or sitaxsentan due to liver function test abnormalities. Chest. 2009 Jan;135(1):122-129. doi: 10.1378/chest.08-1028. Epub 2008 Sep 23.

  PMID: 18812445 DERIVED

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

Seven subjects were excluded from the change from baseline analysis of the SF-36 Health Survey because the incorrect version of the SF-36 questionnaire was used for evaluation at baseline, which made comparisons problematic.

Results Point of Contact

• Title: Annemarie Vance
• Organization: Gilead Sciences, Inc.

Annemarie.Vance@gilead.com

650-524-3829

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2007
• First Posted: January 18, 2007
• Study Start: May 1, 2005
• Primary Completion: January 1, 2006
• Study Completion: March 1, 2009
• Last Updated: June 17, 2013
• Results First Posted: June 20, 2012

Record last verified: 2013-06