Trial Outcomes & Findings for Open-Label Study of Oral Treprostinil in Digital Ulcers (NCT NCT00848107)
NCT ID: NCT00848107
Last Updated: 2024-06-18
Results Overview
Net ulcer burden at any given assessment was defined as the number of "new" or "active" ulcers at that assessment, plus the number of "indeterminate" ulcers at that assessment that had previously been classified as either "active" or "new" at any earlier assessment during the study. The mean change in net ulcer burden from time of study entry was summarized for each scheduled visit assessment.
TERMINATED
PHASE2
115 participants
Baseline and Months 1, 3, 6, 9, 12, and 18
2024-06-18
Participant Flow
Subjects were recruited to enroll in 26 centers in the US, Canada, and the UK in this open-label trial within 14 days of completion of TDE-DU-201. Subjects who prematurely terminated the previous controlled trial were not eligible. Data from the final study visit of the previous trial served as Baseline data and subject blinding was maintained.
Eligible subjects who completed assessments for the final visit of the previous controlled trial, TDE-DU-201, were eligible to enroll in this extension study. Data from this final study visit served as Baseline data. A total of 115 subjects were enrolled, with 115 subjects receiving study medication at an initial dose of 0.25 mg twice daily (BID).
Participant milestones
| Measure |
Oral Treprostinil Diethanolamine
Oral Treprostinil Diethanolamine initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD).
|
|---|---|
|
Overall Study
STARTED
|
115
|
|
Overall Study
COMPLETED
|
94
|
|
Overall Study
NOT COMPLETED
|
21
|
Reasons for withdrawal
| Measure |
Oral Treprostinil Diethanolamine
Oral Treprostinil Diethanolamine initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD).
|
|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Withdrawal by Subject
|
8
|
|
Overall Study
Adverse Event
|
9
|
|
Overall Study
Death
|
1
|
|
Overall Study
Pregnancy
|
1
|
Baseline Characteristics
Open-Label Study of Oral Treprostinil in Digital Ulcers
Baseline characteristics by cohort
| Measure |
Oral Treprostinil Diethanolamine
n=115 Participants
Oral Treprostinil Diethanolamine initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD).
|
|---|---|
|
Age, Continuous
|
50 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
88 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
97 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African-American
|
13 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native American
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not provided
|
1 participants
n=5 Participants
|
|
Years since scleroderma diagnosis
|
10.9 years
n=5 Participants
|
|
Scleroderma Classification
Limited
|
82 participants
n=5 Participants
|
|
Scleroderma Classification
Diffuse
|
33 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Months 1, 3, 6, 9, 12, and 18Population: Efficacy was assessed using data obtained at each visit, if available, from all subjects enrolled in this study. Assessments performed after discontinuation of study drug were excluded from the summaries.
Net ulcer burden at any given assessment was defined as the number of "new" or "active" ulcers at that assessment, plus the number of "indeterminate" ulcers at that assessment that had previously been classified as either "active" or "new" at any earlier assessment during the study. The mean change in net ulcer burden from time of study entry was summarized for each scheduled visit assessment.
Outcome measures
| Measure |
Oral Treprostinil Diethanolamine
n=111 Participants
Oral Treprostinil Diethanolamine initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD).
|
|---|---|
|
Net Ulcer Burden- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 1
|
-0.77 ulcers
Standard Deviation 1.61
|
|
Net Ulcer Burden- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 3
|
-0.52 ulcers
Standard Deviation 2.02
|
|
Net Ulcer Burden- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 6
|
-0.32 ulcers
Standard Deviation 1.19
|
|
Net Ulcer Burden- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 9
|
-0.52 ulcers
Standard Deviation 1.53
|
|
Net Ulcer Burden- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 12
|
-0.64 ulcers
Standard Deviation 1.20
|
|
Net Ulcer Burden- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 18
|
-1.67 ulcers
Standard Deviation 0.58
|
PRIMARY outcome
Timeframe: Baseline and Months 1, 3, 6, 9, 12, and 18Population: Efficacy was assessed by the change in net ulcer burden and in the total ulcer number from Baseline at each of the follow-up visits and the percentage of subjects with formation of new ulcers during the study. Assessments performed after discontinuation of study drug were excluded from the summaries.
The total ulcer number includes all ulcers designated as "active", "indeterminate", or "new" for a given visit. The mean change in the total number of ulcers present from time of study entry was summarized for each scheduled visit assessment.
Outcome measures
| Measure |
Oral Treprostinil Diethanolamine
n=111 Participants
Oral Treprostinil Diethanolamine initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD).
|
|---|---|
|
Total Ulcer Number- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 1
|
-0.23 number of ulcers
Standard Deviation 1.36
|
|
Total Ulcer Number- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 3
|
-0.24 number of ulcers
Standard Deviation 1.99
|
|
Total Ulcer Number- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 6
|
-0.21 number of ulcers
Standard Deviation 1.21
|
|
Total Ulcer Number- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 9
|
-0.46 number of ulcers
Standard Deviation 1.57
|
|
Total Ulcer Number- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 12
|
-0.61 number of ulcers
Standard Deviation 1.20
|
|
Total Ulcer Number- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment
Month 18
|
-1.67 number of ulcers
Standard Deviation 0.58
|
PRIMARY outcome
Timeframe: 18 months (or last study visit)Population: Efficacy was assessed by the change in net ulcer burden and in the total ulcer number from Baseline at each of the follow-up visits and the percentage of subjects with formation of new ulcers during the study. Assessments performed after discontinuation of study drug were excluded from the summaries.
The number and percentage of subjects who developed new ulcers during the study were summarized.
Outcome measures
| Measure |
Oral Treprostinil Diethanolamine
n=115 Participants
Oral Treprostinil Diethanolamine initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD).
|
|---|---|
|
Formation of New Ulcers
No new ulcers
|
48 participants
|
|
Formation of New Ulcers
At least one new ulcer formed
|
63 participants
|
|
Formation of New Ulcers
Indeterminate / missing data
|
4 participants
|
SECONDARY outcome
Timeframe: Baseline and Months 1, 3, 6, and 12Population: Efficacy was assessed by the change in net ulcer burden and in the total ulcer number from Baseline at each of the follow-up visits and the percentage of subjects with formation of new ulcers during the study. Assessments performed after discontinuation of study drug were excluded from the summaries.
The SHAQ consists of 20 health assessment questionnaire questions with integer responses of 0 (without any difficulty) to 3 (unable to do), and five scleroderma-specific visual analog scale (VAS) domains (Overall Disease Activity, Raynaud's Phenomenon, Finger Ulcers, Breathing, and Intestinal Problems) with values ranging from 0.0 to 15.0 centimeters. The questions are divided into eight component domains: Dressing \& Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each domain score is calculated by summing the domain responses and dividing by the number of questions in that domain. Each VAS domain score is calculated by dividing the value in centimeters by 5. SHAQ component and VAS domain score ranges from 0 (least limitation) to 3 (most limitation). The aggregate SHAQ score is calculated by dividing the sum of all domain scores by 13, with a score ranging from 0 (least limitation) to 3 (most limitation).
Outcome measures
| Measure |
Oral Treprostinil Diethanolamine
n=109 Participants
Oral Treprostinil Diethanolamine initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD).
|
|---|---|
|
Patient Function and QOL Measure: Scleroderma Health Assessments Questionnaire (SHAQ)- Mean Change From Study Entry in SHAQ Component Scores at Each Scheduled Assessment
Month 1
|
-0.01 units on a scale
Standard Deviation 0.21
|
|
Patient Function and QOL Measure: Scleroderma Health Assessments Questionnaire (SHAQ)- Mean Change From Study Entry in SHAQ Component Scores at Each Scheduled Assessment
Month 12
|
-0.04 units on a scale
Standard Deviation 0.27
|
|
Patient Function and QOL Measure: Scleroderma Health Assessments Questionnaire (SHAQ)- Mean Change From Study Entry in SHAQ Component Scores at Each Scheduled Assessment
Month 3
|
0.02 units on a scale
Standard Deviation 0.23
|
|
Patient Function and QOL Measure: Scleroderma Health Assessments Questionnaire (SHAQ)- Mean Change From Study Entry in SHAQ Component Scores at Each Scheduled Assessment
Month 6
|
0.02 units on a scale
Standard Deviation 0.28
|
SECONDARY outcome
Timeframe: Baseline and Months 1, 3, 6, and 12Population: Efficacy was assessed by the change in net ulcer burden and in the total ulcer number from Baseline at each of the follow-up visits and the percentage of subjects with formation of new ulcers during the study. Assessments performed after discontinuation of study drug were excluded from the summaries.
The CHFS score is derived from 18 validated questions that assess functional disability and handicap due to hand involvement in rheumatoid arthritis. Each answer is scored on a scale 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), with improvements in function or reduction of limitation indicated a decreased score value. The mean change from study entry in CHFS scores at each scheduled assessment are summarized.
Outcome measures
| Measure |
Oral Treprostinil Diethanolamine
n=109 Participants
Oral Treprostinil Diethanolamine initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD).
|
|---|---|
|
Patient Function and Quality of Life Measure: Cochin Hand Function Scale (CHFS)-Mean Change From Study Entry in CHFS Score at Each Scheduled Assessment
Month 1
|
-1.1 units on a scale
Standard Deviation 9.7
|
|
Patient Function and Quality of Life Measure: Cochin Hand Function Scale (CHFS)-Mean Change From Study Entry in CHFS Score at Each Scheduled Assessment
Month 6
|
-1.0 units on a scale
Standard Deviation 9.3
|
|
Patient Function and Quality of Life Measure: Cochin Hand Function Scale (CHFS)-Mean Change From Study Entry in CHFS Score at Each Scheduled Assessment
Month 3
|
-1.2 units on a scale
Standard Deviation 8.7
|
|
Patient Function and Quality of Life Measure: Cochin Hand Function Scale (CHFS)-Mean Change From Study Entry in CHFS Score at Each Scheduled Assessment
Month 12
|
-2.8 units on a scale
Standard Deviation 9.7
|
Adverse Events
Oral Treprostinil Diethanolamine
Serious adverse events
| Measure |
Oral Treprostinil Diethanolamine
n=115 participants at risk
Oral Treprostinil Diethanolamine initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD).
|
|---|---|
|
Infections and infestations
Gastroenteritis
|
5.2%
6/115 • Number of events 6 • 48 months
|
|
Infections and infestations
Infected skin ulcer
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Infections and infestations
Infection
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Infections and infestations
Osteomyelitis
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Infections and infestations
Pneumonia
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Infections and infestations
Respiratory tract infection
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Blood and lymphatic system disorders
Anemia
|
1.7%
2/115 • Number of events 3 • 48 months
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
1.7%
2/115 • Number of events 2 • 48 months
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Cardiac disorders
Cardiac arrest
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Cardiac disorders
Coronary artery disease
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Cardiac disorders
Pericardial effusion
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
General disorders
Non-cardiac chest pain
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
General disorders
Pyrexia
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Renal and urinary disorders
Renal failure acute
|
1.7%
2/115 • Number of events 2 • 48 months
|
|
Vascular disorders
Femoral artery occlusion
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Vascular disorders
Thrombosis
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Hepatobiliary disorders
Cholecystitis
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma recurrent
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Nervous system disorders
Hypoxic-ischaemic encephalopathy
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Reproductive system and breast disorders
Prostatitis
|
0.87%
1/115 • Number of events 1 • 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchiectasis
|
0.87%
1/115 • Number of events 1 • 48 months
|
Other adverse events
| Measure |
Oral Treprostinil Diethanolamine
n=115 participants at risk
Oral Treprostinil Diethanolamine initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD).
|
|---|---|
|
Nervous system disorders
Headache
|
64.3%
74/115 • Number of events 99 • 48 months
|
|
Nervous system disorders
Dizziness
|
19.1%
22/115 • Number of events 24 • 48 months
|
|
Nervous system disorders
Migraine
|
7.0%
8/115 • Number of events 12 • 48 months
|
|
Gastrointestinal disorders
Diarrhea
|
45.2%
52/115 • Number of events 77 • 48 months
|
|
Gastrointestinal disorders
Nausea
|
33.9%
39/115 • Number of events 53 • 48 months
|
|
Gastrointestinal disorders
Vomiting
|
13.0%
15/115 • Number of events 20 • 48 months
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
10.4%
12/115 • Number of events 13 • 48 months
|
|
Gastrointestinal disorders
Constipation
|
7.8%
9/115 • Number of events 9 • 48 months
|
|
Gastrointestinal disorders
Abdominal discomfort
|
6.1%
7/115 • Number of events 10 • 48 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.1%
7/115 • Number of events 9 • 48 months
|
|
Gastrointestinal disorders
Dyspepsia
|
6.1%
7/115 • Number of events 7 • 48 months
|
|
Gastrointestinal disorders
Flatulence
|
5.2%
6/115 • Number of events 6 • 48 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
25.2%
29/115 • Number of events 39 • 48 months
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
25.2%
29/115 • Number of events 32 • 48 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.5%
19/115 • Number of events 27 • 48 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
15.7%
18/115 • Number of events 20 • 48 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.6%
11/115 • Number of events 12 • 48 months
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.8%
9/115 • Number of events 9 • 48 months
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
5.2%
6/115 • Number of events 6 • 48 months
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.2%
6/115 • Number of events 7 • 48 months
|
|
Infections and infestations
Infected skin ulcer
|
17.4%
20/115 • Number of events 29 • 48 months
|
|
Infections and infestations
Localised infection
|
13.0%
15/115 • Number of events 18 • 48 months
|
|
Infections and infestations
Nasopharyngitis
|
9.6%
11/115 • Number of events 15 • 48 months
|
|
Infections and infestations
Influenza
|
7.0%
8/115 • Number of events 8 • 48 months
|
|
Infections and infestations
Sinusitis
|
6.1%
7/115 • Number of events 7 • 48 months
|
|
General disorders
Fatigue
|
31.3%
36/115 • Number of events 37 • 48 months
|
|
General disorders
Oedema peripheral
|
15.7%
18/115 • Number of events 20 • 48 months
|
|
General disorders
Pain
|
7.0%
8/115 • Number of events 13 • 48 months
|
|
General disorders
Pyrexia
|
5.2%
6/115 • Number of events 7 • 48 months
|
|
General disorders
Asthenia
|
5.2%
6/115 • Number of events 6 • 48 months
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
9.6%
11/115 • Number of events 13 • 48 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.8%
9/115 • Number of events 10 • 48 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.0%
8/115 • Number of events 8 • 48 months
|
|
Vascular disorders
Flushing
|
22.6%
26/115 • Number of events 29 • 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.6%
11/115 • Number of events 11 • 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
9.6%
11/115 • Number of events 12 • 48 months
|
|
Psychiatric disorders
Insomnia
|
15.7%
18/115 • Number of events 19 • 48 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.6%
11/115 • Number of events 11 • 48 months
|
Additional Information
Rex Mauthe, Assoc VP, Regulatory Affairs
United Therapeutics Corporation
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the results of this trial must be consistent with the United Therapeutics publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER