Trial Outcomes & Findings for Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine (NCT NCT00775463)
NCT ID: NCT00775463
Last Updated: 2023-12-28
Results Overview
Net ulcer burden was defined as the number of "new" or "active" digital ulcers (DU), plus the number of "indeterminate" DUs at that assessment that have previously been classified as either "active" or "new" at any earlier assessment during the study. A DU was defined as an area with visually discernable depth and a loss of continuity of epithelial coverage, which could be denuded or covered by a scab or necrotic tissue. If denuded, the DU was pronounced "active." If denudation could not be judged because of the presence of scab or necrotic tissue, DU presenting with features, including underlying pain, based on Investigator clinical judgment to be consistent with loss of epithelialization, epidermis, or dermis, and requiring treatment were designated as "active." Otherwise, the DU was pronounced "indeterminate." Only DUs distal to the proximal interphalangeal joints, volar to the equator of the finger, not localized in creases and vascular in origin were assessed.
COMPLETED
PHASE2
148 participants
Week 20
2023-12-28
Participant Flow
Subjects were recruited across 32 clinical trial sites in the US, Canada and UK experienced in the treatment of systemic sclerosis (SSc) and capable of conducting the trial according to ICH GCP guidance. Subjects were recruited between April 2009 and October 2010.
Participant milestones
| Measure |
Placebo
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|
|
Overall Study
STARTED
|
76
|
72
|
|
Overall Study
COMPLETED
|
65
|
59
|
|
Overall Study
NOT COMPLETED
|
11
|
13
|
Reasons for withdrawal
| Measure |
Placebo
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Adverse Event
|
7
|
9
|
|
Overall Study
Protocol Violation
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Lack of Efficacy
|
1
|
1
|
Baseline Characteristics
Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine
Baseline characteristics by cohort
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=71 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Total
n=147 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
47.8 years
n=5 Participants
|
49.8 years
n=7 Participants
|
48.8 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
55 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
109 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
10 participants
n=5 Participants
|
7 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
62 participants
n=5 Participants
|
59 participants
n=7 Participants
|
121 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
SSc Classification
Limited
|
55 participants
n=5 Participants
|
40 participants
n=7 Participants
|
95 participants
n=5 Participants
|
|
SSc Classification
Diffuse
|
21 participants
n=5 Participants
|
31 participants
n=7 Participants
|
52 participants
n=5 Participants
|
|
Years since SSc diagnosis
|
10.7 years
n=5 Participants
|
10.3 years
n=7 Participants
|
10.5 years
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 20Population: The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change.
Net ulcer burden was defined as the number of "new" or "active" digital ulcers (DU), plus the number of "indeterminate" DUs at that assessment that have previously been classified as either "active" or "new" at any earlier assessment during the study. A DU was defined as an area with visually discernable depth and a loss of continuity of epithelial coverage, which could be denuded or covered by a scab or necrotic tissue. If denuded, the DU was pronounced "active." If denudation could not be judged because of the presence of scab or necrotic tissue, DU presenting with features, including underlying pain, based on Investigator clinical judgment to be consistent with loss of epithelialization, epidermis, or dermis, and requiring treatment were designated as "active." Otherwise, the DU was pronounced "indeterminate." Only DUs distal to the proximal interphalangeal joints, volar to the equator of the finger, not localized in creases and vascular in origin were assessed.
Outcome measures
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=71 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Net Ulcer Burden
Baseline
|
1.0 ulcers
Interval 1.0 to 2.0
|
2.0 ulcers
Interval 1.0 to 2.0
|
—
|
—
|
—
|
—
|
|
Net Ulcer Burden
Change at Week 20
|
0.0 ulcers
Interval -1.0 to 1.0
|
-1.0 ulcers
Interval -1.0 to 0.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 20Population: The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Digital ulcer pain was rated on a 100-mm VAS on which subjects were asked to rate their average overall hand pain during the last week. The recorded value was divided by 10, with values ranging from 0.0 (no pain) to 10.0 (unbearable pain), expressed to one decimal.
Outcome measures
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=70 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Digital Ulcer Pain VAS
Baseline
|
4.85 units on a scale
Interval 2.75 to 6.75
|
6.00 units on a scale
Interval 2.8 to 7.7
|
—
|
—
|
—
|
—
|
|
Digital Ulcer Pain VAS
Change at Week 20
|
-1.05 units on a scale
Interval -3.2 to 0.1
|
-1.45 units on a scale
Interval -4.6 to 0.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 20Population: The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Patients rated their global impression of digital ulcer severity on a 15-cm VAS from scaled 0 (no disease activity) to 100 (very severe disease). The term "severity" was used to measure the extent of disease activity and associated disability or discomfort the patient experienced during the indicated time period.
Outcome measures
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=70 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Patient Global Assessment of Digital Ulcer Severity VAS
Baseline
|
57.0 units on a scale
Interval 29.3 to 79.7
|
67.0 units on a scale
Interval 34.7 to 78.0
|
—
|
—
|
—
|
—
|
|
Patient Global Assessment of Digital Ulcer Severity VAS
Change at Week 20
|
-24.0 units on a scale
Interval -43.0 to 0.0
|
-24.3 units on a scale
Interval -63.3 to -3.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 20Population: The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Physicians rated their global impression of digital ulcer severity on a 15-cm VAS from scaled 0 (no disease activity) to 100 (very severe disease). The term "severity" was used to measure the extent of disease activity and associated disability or discomfort the patient experienced during the indicated time period.
Outcome measures
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=70 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Physician Global Assessment of Digital Ulcer Severity VAS
Baseline
|
44.7 units on a scale
Interval 26.0 to 63.3
|
47.3 units on a scale
Interval 31.3 to 66.7
|
—
|
—
|
—
|
—
|
|
Physician Global Assessment of Digital Ulcer Severity VAS
Change at Week 20
|
-13.3 units on a scale
Interval -31.3 to -1.3
|
-26.7 units on a scale
Interval -43.3 to -5.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 20Population: The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
The CHFS has been demonstrated as a reliable and valid assessment of hand function at the activity level in persons with SSc. It is comprised of 18 questions with possible integer responses of 0 (without difficulty) to 5 (impossible). The CHFS Score is simply the sum of all 18 questions, divided by the number of questions actually answered, multiplied by 18. At least 10 of the 18 questions must have been answered in order for CHFS to be calculated. Therefore, CHFS Score values can range from 0 (least limitation) to 90 (most limitation). A higher score indicates more difficulty in hand function or greater disability.
Outcome measures
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=71 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Cochin Hand Function Scale (CHFS)
Baseline
|
18.5 units on a scale
Interval 5.0 to 29.5
|
24.0 units on a scale
Interval 11.0 to 37.0
|
—
|
—
|
—
|
—
|
|
Cochin Hand Function Scale (CHFS)
Week 20
|
19.0 units on a scale
Interval 4.0 to 33.5
|
21.0 units on a scale
Interval 8.0 to 35.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 20Population: The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
The SHAQ is a patient self-administered instrument which has been previously validated in SSc and demonstrates meaningful clinical changes in the course of the disease over time. It is comprised of a 20 question instrument pertaining to specific activities with possible integer responses of 0 (without any difficulty) to 3 (unable to do), and five additional scleroderma-specific visual analog scale (VAS) domains (Overall Disease Activity, Raynaud's Phenomenon, Finger Ulcers, Breathing, and Intestinal Problems) with possible values ranging from 0.0 to 15.0. The 20 questions are divided into eight domains. A mean score is calculated for each domain ranging from 0 to 3. A composite HAQ DI score is calculated by dividing the summed domain scores by the number of domains answered. The composite score is reported, falling between 0 and 3 on an ordinal scale. The scores are interpreted as 0 (no impairment in function) to 3 (maximal impairment of function).
Outcome measures
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=71 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Dressing & Grooming Score: Baseline (76/71)
|
0.50 units on a scale
Interval 0.0 to 1.0
|
1.00 units on a scale
Interval 0.5 to 1.5
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Dressing&Grooming Score:Change at Week 20
|
0.00 units on a scale
Interval 0.0 to 0.0
|
0.00 units on a scale
Interval -0.5 to 0.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Arising Score: Baseline (76/71)
|
0.00 units on a scale
Interval 0.0 to 1.0
|
0.00 units on a scale
Interval 0.0 to 1.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Arising Score: Change at Week 20
|
0.00 units on a scale
Interval 0.0 to 0.0
|
0.00 units on a scale
Interval 0.0 to 0.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Eating Score: Baseline (76/71)
|
0.67 units on a scale
Interval 0.0 to 1.0
|
0.67 units on a scale
Interval 0.33 to 1.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Eating Score: Change at Week 20
|
0.00 units on a scale
Interval -1.17 to 0.08
|
0.00 units on a scale
Interval -0.33 to 0.17
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Walking Score: Baseline (76/71)
|
0.00 units on a scale
Interval 0.0 to 0.5
|
0.00 units on a scale
Interval 0.0 to 0.5
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Walking Score: Change at Week 20
|
0.00 units on a scale
Interval 0.0 to 0.0
|
0.00 units on a scale
Interval 0.0 to 0.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Hygiene Score: Baseline (76/68)
|
0.00 units on a scale
Interval 0.0 to 0.67
|
0.33 units on a scale
Interval 0.0 to 0.67
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Hygiene Score: Change at Week 20
|
0.00 units on a scale
Interval 0.0 to 0.33
|
0.00 units on a scale
Interval 0.0 to 0.33
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Reach Score: Baseline (76/68)
|
0.00 units on a scale
Interval 0.0 to 1.0
|
0.50 units on a scale
Interval 0.0 to 1.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Reach Score: Change at Week 20
|
0.00 units on a scale
Interval 0.0 to 0.0
|
0.00 units on a scale
Interval 0.0 to 0.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Grip Score: Baseline (76/68)
|
0.33 units on a scale
Interval 0.0 to 0.67
|
0.33 units on a scale
Interval 0.17 to 1.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Grip Score: Change at Week 20
|
0.00 units on a scale
Interval 0.0 to 0.33
|
0.00 units on a scale
Interval -0.33 to 0.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Activity Score: Baseline (76/68)
|
0.33 units on a scale
Interval 0.0 to 1.0
|
0.67 units on a scale
Interval 0.0 to 1.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Activity Score: Change at Week 20
|
0.00 units on a scale
Interval 0.0 to 0.33
|
0.00 units on a scale
Interval 0.0 to 0.17
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
HAQ Aggregate Score: Baseline (76/68)
|
0.34 units on a scale
Interval 0.1 to 0.77
|
0.53 units on a scale
Interval 0.26 to 0.81
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
HAQ Aggregate Score: Change at Week 20
|
0.00 units on a scale
Interval -0.07 to 0.13
|
-0.03 units on a scale
Interval -0.16 to 0.12
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Hand Function Aggregate Score: Baseline (76/68)
|
0.39 units on a scale
Interval 0.11 to 0.69
|
0.56 units on a scale
Interval 0.28 to 0.86
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Hand Function Aggregate Score: Change at Week 20
|
0.00 units on a scale
Interval -0.06 to 0.17
|
0.00 units on a scale
Interval -0.22 to 0.11
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Raynaud's Phenomenon VAS Score: Baseline (75/71)
|
0.12 units on a scale
Interval 0.0 to 0.64
|
0.18 units on a scale
Interval 0.02 to 0.8
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Raynaud's Phenomenon VAS Score: Change at Week 20
|
0.00 units on a scale
Interval -0.14 to 0.08
|
0.00 units on a scale
Interval -0.14 to 0.14
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Intestinal Problems VAS Score: Baseline (75/70)
|
0.20 units on a scale
Interval 0.0 to 0.7
|
0.11 units on a scale
Interval 0.02 to 0.62
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Intestinal Problems VAS Score: Change at Week 20
|
0.00 units on a scale
Interval -0.1 to 0.24
|
0.11 units on a scale
Interval -0.02 to 0.72
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Digital Ulcer VAS Score: Baseline (76/71)
|
1.43 units on a scale
Interval 0.49 to 2.09
|
1.50 units on a scale
Interval 0.68 to 2.28
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Digital Ulcer VAS Score: Change at Week 20
|
-0.34 units on a scale
Interval -0.92 to 0.0
|
-0.56 units on a scale
Interval -1.36 to 0.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Breathing Problems VAS Score: Baseline (76/71)
|
1.54 units on a scale
Interval 0.95 to 2.31
|
2.16 units on a scale
Interval 0.96 to 2.54
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Breathing Problems VAS Score: Change at Week 20
|
-0.50 units on a scale
Interval -1.15 to 0.0
|
-0.84 units on a scale
Interval -2.14 to -0.2
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Pain VAS Score: Baseline (76/69)
|
1.27 units on a scale
Interval 0.57 to 1.91
|
1.54 units on a scale
Interval 0.54 to 2.16
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Pain VAS Score: Change at Week 20
|
-0.26 units on a scale
Interval -0.93 to 0.11
|
-0.34 units on a scale
Interval -1.44 to 0.0
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Overall Disease VAS Score: Baseline (76/71)
|
1.22 units on a scale
Interval 0.67 to 1.87
|
1.52 units on a scale
Interval 0.74 to 2.12
|
—
|
—
|
—
|
—
|
|
Scleroderma Health Assessment Questionnaire (SHAQ)
Overall Disease VAS Score: Change at Week 20
|
-0.18 units on a scale
Interval -0.6 to 0.04
|
-0.32 units on a scale
Interval -1.0 to 0.1
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 20Population: The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
The skin thickening was assessed by the Investigator in 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Each area was scored 0-3; 0 representing normal skin and 3 being severe thickening. The mRSS was the sum of the individual skin assessment scores: possible range of 0-51; 0 (no thickening) to 51 (severe thickening in all 17 areas) .
Outcome measures
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=71 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Modified Rodnan Skin Score (mRSS)
Baseline
|
6.0 units on a scale
Interval 3.0 to 12.0
|
8.0 units on a scale
Interval 5.0 to 14.0
|
—
|
—
|
—
|
—
|
|
Modified Rodnan Skin Score (mRSS)
Week 20
|
6.0 units on a scale
Interval 3.0 to 12.0
|
6.0 units on a scale
Interval 3.0 to 15.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 20Population: The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
The SF-MPQ assessment has three component scores: the pain rating index (PRI), a pain visual analogue numerical scale (Pain VAS) and the present pain intensity (PPI). PRI is calculated by summing the responses (0=None to 3=Severe) to the 15 questions describing pain during the previous week and rated on an intensity scale as 0= none, 1= mild, 2= moderate or 3= severe and has possible values ranging from 0 to 45. The Pain VAS is a 100 mm VAS on which subjects were asked to rate pain during the previous week with values ranging from no pain (0.0) to worst possible pain (10.0). The PPI rated pain on a 6-point category scale from 0 (no pain) to 5 (excruciating pain).
Outcome measures
| Measure |
Placebo
n=74 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=68 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Short-Form McGill Pain Questionnaire
Total Pain Rating Index Score Change at Week 20
|
-4.0 units on a scale
Interval -8.0 to 1.0
|
-3.0 units on a scale
Interval -12.0 to 0.0
|
—
|
—
|
—
|
—
|
|
Short-Form McGill Pain Questionnaire
Pain VAS Score Change at Week 20
|
-0.6 units on a scale
Interval -2.9 to 0.3
|
-1.1 units on a scale
Interval -4.4 to 0.2
|
—
|
—
|
—
|
—
|
|
Short-Form McGill Pain Questionnaire
Present Pain Intensity Score Change at Week 20
|
0.0 units on a scale
Interval -1.0 to 0.0
|
-1.0 units on a scale
Interval -1.0 to 0.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 20Population: The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
The PIC questionnaire consisted of three Likert items that asked the subject to rate changes in their digital ulcer, Raynaud's phenomenon and disease status since their last visit on a seven-level scale (very much improved, much improved, somewhat improved, same, somewhat worse, much worse and very much worse).
Outcome measures
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=71 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
n=71 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
n=71 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Patient Impression of Change (PIC) Questionnaire
Very Much Improved
|
5 participants
|
9 participants
|
0 participants
|
3 participants
|
0 participants
|
3 participants
|
|
Patient Impression of Change (PIC) Questionnaire
Much Improved
|
11 participants
|
15 participants
|
4 participants
|
12 participants
|
5 participants
|
17 participants
|
|
Patient Impression of Change (PIC) Questionnaire
Somewhat Improved
|
20 participants
|
14 participants
|
12 participants
|
20 participants
|
22 participants
|
13 participants
|
|
Patient Impression of Change (PIC) Questionnaire
Same
|
24 participants
|
21 participants
|
40 participants
|
30 participants
|
30 participants
|
27 participants
|
|
Patient Impression of Change (PIC) Questionnaire
Somewhat Worse
|
14 participants
|
8 participants
|
17 participants
|
4 participants
|
18 participants
|
10 participants
|
|
Patient Impression of Change (PIC) Questionnaire
Much Worse
|
1 participants
|
3 participants
|
1 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Patient Impression of Change (PIC) Questionnaire
Very Much Worse
|
1 participants
|
1 participants
|
2 participants
|
1 participants
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Week 20Population: The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Change in patient quality of life was measured by the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), a self-administered questionnaire covering eight areas: physical function, physical role, bodily pain, general health, vitality, social function, emotional role, and mental health. For each area, the score range from 0 (poorer health status) to 100 (better health status). The SF-36 is one of the most widely used and validated instruments to assess quality of life in patients with systemic illnesses. A decrease (negative change) in a domain score corresponds to deterioration.
Outcome measures
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=71 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Short Form 36
Physical Component: Baseline
|
55.0 units on a scale
Interval 39.5 to 67.5
|
50.7 units on a scale
Interval 35.1 to 62.9
|
—
|
—
|
—
|
—
|
|
Short Form 36
Physical Component: Change at Week 20
|
2.8 units on a scale
Interval -5.3 to 10.9
|
3.8 units on a scale
Interval -2.1 to 10.3
|
—
|
—
|
—
|
—
|
|
Short Form 36
Physical Functioning: Baseline
|
62.5 units on a scale
Interval 30.0 to 80.0
|
60.0 units on a scale
Interval 35.0 to 75.0
|
—
|
—
|
—
|
—
|
|
Short Form 36
Physical Functioning: Change at Week 20
|
0.0 units on a scale
Interval -5.0 to 10.0
|
0.0 units on a scale
Interval -10.0 to 10.0
|
—
|
—
|
—
|
—
|
|
Short Form 36
Role-Physical: Baseline
|
54.4 units on a scale
Interval 37.5 to 72.5
|
50.0 units on a scale
Interval 25.0 to 70.0
|
—
|
—
|
—
|
—
|
|
Short Form 36
Role-Physical: Change at Week 20
|
0.0 units on a scale
Interval -10.0 to 17.5
|
0.0 units on a scale
Interval 0.0 to 22.5
|
—
|
—
|
—
|
—
|
|
Short Form 36
Bodily Pain: Baseline
|
57.5 units on a scale
Interval 33.8 to 67.5
|
45.0 units on a scale
Interval 32.5 to 75.0
|
—
|
—
|
—
|
—
|
|
Short Form 36
Bodily Pain: Change at Week 20
|
10.0 units on a scale
Interval -5.0 to 21.3
|
10.0 units on a scale
Interval -2.5 to 22.5
|
—
|
—
|
—
|
—
|
|
Short Form 36
General Health: Baseline
|
42.0 units on a scale
Interval 34.0 to 65.0
|
45.0 units on a scale
Interval 30.0 to 63.0
|
—
|
—
|
—
|
—
|
|
Short Form 36
General Health: Change at Week 20
|
0.0 units on a scale
Interval -9.5 to 5.0
|
0.0 units on a scale
Interval -5.0 to 6.0
|
—
|
—
|
—
|
—
|
|
Short Form 36
Mental Component: Baseline
|
68.3 units on a scale
Interval 54.1 to 77.4
|
64.2 units on a scale
Interval 49.2 to 76.1
|
—
|
—
|
—
|
—
|
|
Short Form 36
Mental Component: Change at Week 20
|
2.6 units on a scale
Interval -8.6 to 11.0
|
4.0 units on a scale
Interval -4.0 to 15.7
|
—
|
—
|
—
|
—
|
|
Short Form 36
Vitality: Baseline (75/71)
|
50.0 units on a scale
Interval 31.3 to 62.5
|
43.8 units on a scale
Interval 25.0 to 61.3
|
—
|
—
|
—
|
—
|
|
Short Form 36
Vitality: Change at Week 20
|
0.0 units on a scale
Interval -6.3 to 7.5
|
1.3 units on a scale
Interval -6.3 to 17.5
|
—
|
—
|
—
|
—
|
|
Short Form 36
Social Functioning: Baseline
|
72.5 units on a scale
Interval 50.0 to 87.5
|
62.5 units on a scale
Interval 50.0 to 85.0
|
—
|
—
|
—
|
—
|
|
Short Form 36
Social Functioning: Change at Week 20
|
0.0 units on a scale
Interval -12.5 to 13.8
|
10.0 units on a scale
Interval 0.0 to 22.5
|
—
|
—
|
—
|
—
|
|
Short Form 36
Role-Emotional: Baseline
|
70.0 units on a scale
Interval 60.8 to 95.0
|
80.0 units on a scale
Interval 50.0 to 100.0
|
—
|
—
|
—
|
—
|
|
Short Form 36
Role-Emotional: Change at Week 20
|
0.0 units on a scale
Interval -5.8 to 11.7
|
0.0 units on a scale
Interval -1.7 to 13.3
|
—
|
—
|
—
|
—
|
|
Short Form 36
Mental Health: Baseline (75/71)
|
69.0 units on a scale
Interval 52.0 to 84.0
|
64.0 units on a scale
Interval 54.0 to 79.0
|
—
|
—
|
—
|
—
|
|
Short Form 36
Mental Health: Change at Week 20
|
2.0 units on a scale
Interval -6.0 to 11.0
|
3.0 units on a scale
Interval -5.0 to 16.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 20A subject was counted as having all ulcers completely healed at the earliest assessment for which all ulcers are designated as "healed" and no new ulcers appeared for the remainder of the trial.
Outcome measures
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=71 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Time to Ulcer Healing- Percentage of Subjects With Complete Healing
Cardinal Ulcer Healed
|
61 percentage of participants
|
62 percentage of participants
|
—
|
—
|
—
|
—
|
|
Time to Ulcer Healing- Percentage of Subjects With Complete Healing
All Ulcers Healed
|
41 percentage of participants
|
49 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 20A subject was counted as having all ulcers completely healed at the earliest assessment for which all ulcers are designated as "healed" and no new ulcers appeared for the remainder of the trial. The time to complete healing of all ulcers were calculated as the number of days from randomization to the date of these respective assessments, provided that complete healing was achieved during the study.
Outcome measures
| Measure |
Placebo
n=76 Participants
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=71 Participants
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Raynaud's Phenomenon Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Raynaud's Phenomenon Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Placebo- Overall Disease Status Response
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine- Overall Disease Status Response
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|---|---|---|---|
|
Time to Ulcer Healing
Time to Cardinal Ulcer Healing
|
83.2 days
Standard Deviation 37.9
|
76.3 days
Standard Deviation 35
|
—
|
—
|
—
|
—
|
|
Time to Ulcer Healing
Time to All Ulcers Healed
|
96.7 days
Standard Deviation 39.7
|
90.2 days
Standard Deviation 35.6
|
—
|
—
|
—
|
—
|
Adverse Events
Placebo
Treprostinil Diethanolamine
Serious adverse events
| Measure |
Placebo
n=76 participants at risk
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=71 participants at risk
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
1.3%
1/76 • Number of events 1 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Infections and infestations
Cellulitis
|
1.3%
1/76 • Number of events 1 • 20 weeks
|
0.00%
0/71 • 20 weeks
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/76 • 20 weeks
|
2.8%
2/71 • Number of events 4 • 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.3%
1/76 • Number of events 1 • 20 weeks
|
0.00%
0/71 • 20 weeks
|
|
Gastrointestinal disorders
Vomiting
|
1.3%
1/76 • Number of events 1 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Gastrointestinal disorders
Erosive oesophagitis
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Cardiac disorders
Tachyarrhythmia
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
General disorders
Device dislocation
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Musculoskeletal and connective tissue disorders
Scleroderma
|
1.3%
1/76 • Number of events 1 • 20 weeks
|
0.00%
0/71 • 20 weeks
|
|
Nervous system disorders
Syncope
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Vascular disorders
Hypotension
|
0.00%
0/76 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
Other adverse events
| Measure |
Placebo
n=76 participants at risk
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
Treprostinil Diethanolamine
n=71 participants at risk
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
|
|---|---|---|
|
Nervous system disorders
Headache
|
42.1%
32/76 • Number of events 46 • 20 weeks
|
73.2%
52/71 • Number of events 71 • 20 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
21.1%
16/76 • Number of events 21 • 20 weeks
|
56.3%
40/71 • Number of events 48 • 20 weeks
|
|
General disorders
Fatigue
|
19.7%
15/76 • Number of events 15 • 20 weeks
|
22.5%
16/71 • Number of events 18 • 20 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
15.8%
12/76 • Number of events 16 • 20 weeks
|
16.9%
12/71 • Number of events 13 • 20 weeks
|
|
Skin and subcutaneous tissue disorders
Infected skin ulcer
|
13.2%
10/76 • Number of events 13 • 20 weeks
|
18.3%
13/71 • Number of events 16 • 20 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
5.3%
4/76 • Number of events 5 • 20 weeks
|
23.9%
17/71 • Number of events 20 • 20 weeks
|
|
Vascular disorders
Flushing
|
3.9%
3/76 • Number of events 3 • 20 weeks
|
23.9%
17/71 • Number of events 19 • 20 weeks
|
|
General disorders
Oedema peripheral
|
14.5%
11/76 • Number of events 12 • 20 weeks
|
12.7%
9/71 • Number of events 10 • 20 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.8%
9/76 • Number of events 9 • 20 weeks
|
15.5%
11/71 • Number of events 11 • 20 weeks
|
|
Gastrointestinal disorders
Vomiting
|
5.3%
4/76 • Number of events 5 • 20 weeks
|
16.9%
12/71 • Number of events 18 • 20 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.6%
5/76 • Number of events 6 • 20 weeks
|
15.5%
11/71 • Number of events 13 • 20 weeks
|
|
Nervous system disorders
Dizziness
|
10.5%
8/76 • Number of events 9 • 20 weeks
|
11.3%
8/71 • Number of events 9 • 20 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.3%
4/76 • Number of events 4 • 20 weeks
|
15.5%
11/71 • Number of events 11 • 20 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.9%
6/76 • Number of events 7 • 20 weeks
|
11.3%
8/71 • Number of events 9 • 20 weeks
|
|
General disorders
Pain
|
1.3%
1/76 • Number of events 1 • 20 weeks
|
16.9%
12/71 • Number of events 18 • 20 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.3%
4/76 • Number of events 4 • 20 weeks
|
11.3%
8/71 • Number of events 8 • 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.9%
6/76 • Number of events 7 • 20 weeks
|
7.0%
5/71 • Number of events 6 • 20 weeks
|
|
Gastrointestinal disorders
Abdominal discomfort
|
1.3%
1/76 • Number of events 1 • 20 weeks
|
14.1%
10/71 • Number of events 11 • 20 weeks
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
9.2%
7/76 • Number of events 7 • 20 weeks
|
5.6%
4/71 • Number of events 4 • 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
10.5%
8/76 • Number of events 8 • 20 weeks
|
4.2%
3/71 • Number of events 3 • 20 weeks
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
5.3%
4/76 • Number of events 7 • 20 weeks
|
7.0%
5/71 • Number of events 6 • 20 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.3%
4/76 • Number of events 5 • 20 weeks
|
8.5%
6/71 • Number of events 6 • 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
9.2%
7/76 • Number of events 8 • 20 weeks
|
4.2%
3/71 • Number of events 3 • 20 weeks
|
|
Infections and infestations
Localised infection
|
6.6%
5/76 • Number of events 5 • 20 weeks
|
7.0%
5/71 • Number of events 5 • 20 weeks
|
|
Gastrointestinal disorders
Abdominal distension
|
6.6%
5/76 • Number of events 6 • 20 weeks
|
5.6%
4/71 • Number of events 4 • 20 weeks
|
|
Gastrointestinal disorders
Constipation
|
3.9%
3/76 • Number of events 3 • 20 weeks
|
7.0%
5/71 • Number of events 5 • 20 weeks
|
|
Psychiatric disorders
Insomnia
|
5.3%
4/76 • Number of events 4 • 20 weeks
|
7.0%
5/71 • Number of events 5 • 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.9%
6/76 • Number of events 7 • 20 weeks
|
2.8%
2/71 • Number of events 3 • 20 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
3.9%
3/76 • Number of events 4 • 20 weeks
|
7.0%
5/71 • Number of events 5 • 20 weeks
|
|
Renal and urinary disorders
Urinary tract infection
|
5.3%
4/76 • Number of events 5 • 20 weeks
|
5.6%
4/71 • Number of events 4 • 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.9%
6/76 • Number of events 6 • 20 weeks
|
2.8%
2/71 • Number of events 2 • 20 weeks
|
|
Gastrointestinal disorders
Dyspepsia
|
5.3%
4/76 • Number of events 4 • 20 weeks
|
2.8%
2/71 • Number of events 3 • 20 weeks
|
|
Nervous system disorders
Migraine
|
2.6%
2/76 • Number of events 2 • 20 weeks
|
5.6%
4/71 • Number of events 6 • 20 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.6%
2/76 • Number of events 2 • 20 weeks
|
5.6%
4/71 • Number of events 5 • 20 weeks
|
|
Nervous system disorders
Paraesthesia
|
1.3%
1/76 • Number of events 1 • 20 weeks
|
7.0%
5/71 • Number of events 6 • 20 weeks
|
|
General disorders
Chest pain
|
5.3%
4/76 • Number of events 4 • 20 weeks
|
1.4%
1/71 • Number of events 1 • 20 weeks
|
|
Vascular disorders
Peripheral ischaemia
|
5.3%
4/76 • Number of events 4 • 20 weeks
|
0.00%
0/71 • 20 weeks
|
|
Gastrointestinal disorders
Nausea
|
18.4%
14/76 • Number of events 16 • 20 weeks
|
59.2%
42/71 • Number of events 49 • 20 weeks
|
Additional Information
Oral Treprostinil Program Head
United Therapeutics Corporation
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER