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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01100736
Other study ID # 2008/W/CRC/01
Secondary ID 08/S1102/1
Status Completed
Phase Phase 0
First received March 30, 2010
Last updated July 20, 2015
Start date January 2009
Est. completion date January 2010

Study information

Verified date July 2015
Source University of Edinburgh
Contact n/a
Is FDA regulated No
Health authority United Kingdom: Research Ethics Committee
Study type Interventional

Clinical Trial Summary

Endothelin-1 (ET-1) has been linked to a number of conditions including pulmonary arterial hypertension (PAH). ET-1 acts via 2 receptors, ETA and ETB. The ET-1 receptor blockers bosentan and sitaxsentan have been shown to be beneficial in patients with PAH. Bosentan blocks both ETA and ETB receptors. Sitaxsentan selectively blocks ETA receptors. Theoretically, selective ETA blockade may be associated with greater vasodilation and clearance of ET-1 by leaving the ETB receptor unblocked. This has not been directly studied in humans.

We aim to investigate the endothelial ETB-mediated vascular responses between bosentan and sitaxsentan by using a ETB selective agonist (ET-3). We hypothesise that at clinically relevant doses:

- Bosentan will show evidence of ETB receptor blockade compared to sitaxsentan and placebo.

- These effects will be confirmed by 2 functional markers of ETB receptor antagonism: plasma ET-1 (a very sensitive, but not necessarily clinically relevant marker), and the forearm vasodilator response to ET-3.


Recruitment information / eligibility

Status Completed
Enrollment 10
Est. completion date January 2010
Est. primary completion date September 2009
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years to 70 Years
Eligibility Inclusion Criteria:

- Healthy men and post-menopausal women

- Age 18-70 years

- BMI 18-35 kg/m2

Exclusion Criteria:

- Are mentally or legally incapacitated

- Have donated blood within the last 4 weeks

- Have a history of past or present drug or alcohol abuse

- Have participated in another clinical trial within 1 month

- Are considered to be at a high risk of HIV or Hepatitis B

- Are taking routine medicines

- Are women taking hormone replacement therapy

- Have significant medical or psychiatric illness

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science


Intervention

Drug:
Bosentan
Bosentan 125mg tablets, orally, twice daily for 7 days
Sitaxsentan
Sitaxsentan 100mg tablets, orally, once daily for 7 days
Placebo
Placebo tablets taken twice daily, orally, for 7 days (placebo arm) or once daily for 7 days (sitaxsentan arm)
Biological:
Endothelin-3
5 minute local intra-arterial infusion of endothelin-3 at a rate of rate of 60 pmol/min, during forearm blood flow studies

Locations

Country Name City State
United Kingdom Clinical Research Centre, Western General Hospital Edinburgh Scotland

Sponsors (2)

Lead Sponsor Collaborator
University of Edinburgh Encysive Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Plasma ET-1 after 7-day administration of bosentan, sitaxsentan and placebo 7 days No
Primary Responses to ET-3 (maximum vasodilation after ET-3 administration and area under the curve of vasodilation) after bosentan compared with the results from sitaxsentan and placebo. 60 mins No
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