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Study of Ambrisentan With Antifibrotic Agent Combination Therapy in Diffuse Systemic Sclerosis

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ClinicalTrials.gov Identifier: NCT01093885
Recruitment Status : Completed
First Posted : March 26, 2010
Results First Posted : November 29, 2018
Last Update Posted : November 29, 2018
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
University of Pennsylvania

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Systemic Sclerosis
Scleroderma
Intervention Drug: Ambrisentan
Enrollment 15
Recruitment Details Recruitment took place in the clinic over a 5 year period
Pre-assignment Details None of the patients were able to increase the dosage of ambrisentan from the initial dose of 5 mg to 10 mg.
Arm/Group Title Open Label: Medication Ambrisentan
Hide Arm/Group Description

Open label study of Ambrisentan.

Ambrisentan will begin at 5mg daily for the first month.

Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.

Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin

Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.

Period Title: Overall Study
Started 15
Completed 10
Not Completed 5
Reason Not Completed
Adverse Event             4
Lost to Follow-up             1
Arm/Group Title Open Label: Medication Ambrisentan
Hide Arm/Group Description

Open label study of Ambrisentan.

Ambrisentan will begin at 5mg daily for the first month.

Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.

Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin

Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.

Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
Participant number as per power calculation, less is worse
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
47.6  (10.7)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
10
  66.7%
Male
5
  33.3%
[1]
Measure Description: Consecutive patients referred to the study
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 15 participants
15
 100.0%
Extent of skin sclerosis   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 15 participants
21  (7.4)
[1]
Measure Description: Modified Rodnan Skin Score (mRss), subjective skin scoring of 17 different areas on the body based on a score of 0 to 3 for each side based on the severity of skin tightness of each side, physician assessment, scale from 0-51 points with worse scores at the higher end of the range.
1.Primary Outcome
Title The Benefit That an Antifibrotic Agent and Ambrisentan Combination Have on the Cutaneous Involvement of Patients With Early Diffuse Systemic Sclerosis by Utilizing the MRSS
Hide Description Using validated clinical response measurements such as the modified Rodnan skin score (MRSS) we will determine whether combination therapy will effect morbidity in systemic sclerosis. The modified Rodnan skin score has a range from 0-51 with higher numbers being worse skin involvement.
Time Frame Baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Open Label: Medication Ambrisentan
Hide Arm/Group Description:

Open label study of Ambrisentan.

Ambrisentan will begin at 5mg daily for the first month.

Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.

Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin

Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.

Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: units on a scale
mRss mean for group at study entry 21  (7.4)
mRss mean for group at end of Study- to 12 months 13  (11.2)
2.Secondary Outcome
Title Systemic Sclerosis Quality of Life Assessed by the SF-36.
Hide Description The SF-36 form is a patient reported survey of patient health. The comparison status was analyzed between baseline and 12 months. The SF-36 has a range of 0-100 with higher numbers suggestive of better patient health
Time Frame Baseline vs Month 12.
Hide Outcome Measure Data
Hide Analysis Population Description
15 subjects enrolled, 5 subjects withdrew. Data analyzed was only for the 10 subjects who completed the 12 month visit and had both a baseline and a 12 month SF-36 form completed
Arm/Group Title Open Label: Medication Ambrisentan
Hide Arm/Group Description:

Open label study of Ambrisentan.

Ambrisentan will begin at 5mg daily for the first month.

Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.

** Dose escalation was attempted however none of the patients were able to increase. Therefore all subjects remained on 5 mg daily throughout the study.

Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin

Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.

Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
SF-36 mean for group at study entry 62  (23.3)
SF-36 mean of group at study end -12 months 65.9  (25.7)
Time Frame 1 year
Adverse Event Reporting Description Serious Adverse Events Other Adverse Events
 
Arm/Group Title Open Label: Medication Ambrisentan
Hide Arm/Group Description

Open label study of Ambrisentan.

Ambrisentan will begin at 5mg daily for the first month.

Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.

Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin

Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.

All-Cause Mortality
Open Label: Medication Ambrisentan
Affected / at Risk (%)
Total   0/15 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Open Label: Medication Ambrisentan
Affected / at Risk (%) # Events
Total   4/15 (26.67%)    
Blood and lymphatic system disorders   
Anemia   1/15 (6.67%)  1
Gastrointestinal disorders   
Adynamic ileus   1/15 (6.67%)  1
Product Issues   
Lower Extremity Swelling   1/15 (6.67%)  1
Skin and subcutaneous tissue disorders   
Pruritis   1/15 (6.67%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Open Label: Medication Ambrisentan
Affected / at Risk (%) # Events
Total   15/15 (100.00%)    
Cardiac disorders   
Hypertension   1/15 (6.67%)  1
Ankle Swelling   4/15 (26.67%)  4
Hypotension   1/15 (6.67%)  1
Eye disorders   
Cataract Removal   1/15 (6.67%)  1
Gastrointestinal disorders   
Gastrointestinal illness   3/15 (20.00%)  3
Increased Reflux   1/15 (6.67%)  1
General disorders   
Hot flashes   1/15 (6.67%)  1
Facial Flushing   1/15 (6.67%)  1
Dizziness   2/15 (13.33%)  2
Fatigue   1/15 (6.67%)  1
Mouth Ulcers   1/15 (6.67%)  1
Immune system disorders   
Flu   1/15 (6.67%)  1
Infections and infestations   
Sore throat   1/15 (6.67%)  1
Urinary Tract Infection   1/15 (6.67%)  3
Nasal congestion   3/15 (20.00%)  3
Musculoskeletal and connective tissue disorders   
Shoulder Pain   1/15 (6.67%)  1
Bilateral Flank Pain   1/15 (6.67%)  1
Bilateral Finger Swelling   1/15 (6.67%)  1
Bilateral Wrist Swelling   1/15 (6.67%)  1
Bursitis   1/15 (6.67%)  1
Leg Cramps   1/15 (6.67%)  1
Left Upper Quadrant Pain   1/15 (6.67%)  1
Joint Pain   1/15 (6.67%)  1
Right Shoulder Weakness   1/15 (6.67%)  1
Right Hip Weakness   1/15 (6.67%)  1
Nervous system disorders   
Headache   1/15 (6.67%)  1
Respiratory, thoracic and mediastinal disorders   
Shortness of Breath   1/15 (6.67%)  1
Skin and subcutaneous tissue disorders   
Rash   2/15 (13.33%)  2
Basal Cell Skin cancer   1/15 (6.67%)  1
Indicates events were collected by systematic assessment
Dose escalation was attempted however none of the patients were able to increase. Therefore all subjects remained on 5 mg daily throughout the study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Chris Derk
Organization: University of Pennsylvania Health System
Phone: 215-662-2792
EMail: chris.derk@uphs.upenn.edu
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01093885     History of Changes
Other Study ID Numbers: Ambrj55501.
First Submitted: March 24, 2010
First Posted: March 26, 2010
Results First Submitted: October 16, 2017
Results First Posted: November 29, 2018
Last Update Posted: November 29, 2018