Systemic SclerosisPhase 1DISTOL-PKNCT00848939
Pharmacokinetics of Oral Treprostinil in Patients With Systemic Sclerosis
A Phase 1 study testing treprostinil diethanolamine in people with Systemic Sclerosis, run by United Therapeutics at 3 sites in United States.
Trial summary
This study will assess the pharmacokinetic and safety profile of treprostinil following fixed and escalating doses of treprostinil diethanolamine SR tablets. Open-label, two-part study assessing the pharmacokinetics, safety, and tolerability of oral treprostinil diethanolamine SR. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Sclerosis
- What is being tested?
- treprostinil diethanolamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 3 sitesUnited States
- Study dates
- Dec 2008to Apr 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject gives voluntary written informed consent to participate in the study.
- Subject has been diagnosed with systemic sclerosis (SSc) as defined by American College of Rheumatology (ACR) criteria.
- Males and females age greater than 18 years at time of Screening.
- Presence of active digital ulcer OR history of digital ulcer occurring within past 6 months at time of Screening and poorly controlled Raynaud's phenomenon (as documented by patient report of 6-10 episodes per week).
- Females of childbearing potential must be willing to use two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at Screening, confirmed at Baseline if separate visits. Women who are surgically sterile or have been post-menopausal for at least 2 years are not considered to be of child-bearing potential.
- Subject agrees to abstain from consuming grapefruit containing food or beverages for 3 days prior to Baseline and until discharge from the study.
- Subject is able to communicate effectively with study personnel and be considered reliable, willing and cooperative in terms of compliance with the protocol requirements.
Who cannot join
- Has diagnosis of pulmonary arterial hypertension and receiving approved or investigational therapies for PAH, including endothelin receptor antagonists, phosphodiesterase inhibitors, or prostacyclin analogues.
- Body weight less than 40 kg at time of Screening, confirmed at Baseline.
- The subject has a history of postural hypotension, unexplained syncope, a blood pressure that is less than 85 mmHg systolic or 50 mmHg diastolic at Screening or Baseline.
- Hemoglobin concentration less than 75% of the lower limit of the normal range at time of Screening.
- AST and/or ALT concentrations greater than 3 times upper limit of normal (ULN) at time of Screening.
- Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
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- Intractable diarrhea, severe malabsorption, defined as greater than 15% unintentional loss of body weight in the last 6 months prior to Screening, or any severe organ failure (e.g., lung, kidney) or any life-threatening condition.
- Pregnancy or breast-feeding.
- Overlap with another connective tissue disease that could affect rest pain and hand function (e.g. diabetes mellitus, rheumatoid arthritis).
- Sympathectomy of the upper limb performed within 12 months of Baseline.
- Receipt of parenteral prostanoid treatment (epoprostenol, treprostinil sodium, or other prostacyclin analog) within the previous 3 months for conditions including PAH, rest pain and / or digital ulcers.
- Treatment with gemfibrozil, glitazones, or cyclophosphamide within 1 week prior to Baseline.
- Treatment with rifampin within 4 weeks prior to Baseline.
- Local injection of botulinum toxin in an affected finger within 1 month prior to Baseline.
- Received systemic antibiotics to treat infection of digital ulcers within 2 weeks prior to Baseline.
- Treatment with phosphodiesterase inhibitors such as sildenafil, except for intermittent treatment of male erectile dysfunction.
- Received an investigational product within 1 month preceding Screening.
- Known hypersensitivity to oral treprostinil or any of the excipients.
- Cigarette smoking at any level within the past 6 months prior to Screening.
- Any condition that could prevent compliance with the protocol or adherence to therapy.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Michigan Scleroderma Program
Ann Arbor, Michigan, 48016
Johns Hopkins Scleroderma Center
Baltimore, Maryland, 21224
Boston University School of Medicine Rheumatology Arthritis Center
Boston, Massachusetts, 02118
About this study
Official title: An Evaluation of the Pharmacokinetics and Safety of Fixed and Escalating Doses of Oral Treprostinil Diethanolamine (UT-15C) Sustained Release Tablets in Patients With Systemic Sclerosis
This study will assess the pharmacokinetic and safety profile of treprostinil following fixed and escalating doses of treprostinil diethanolamine SR tablets. Open-label, two-part study assessing the pharmacokinetics, safety, and tolerability of oral treprostinil diethanolamine SR. Cohort 1: single 1 mg treprostinil diethanolamine SR dose. Cohort 2: escalating doses of treprostinil diethanolamine SR up to a target dose of 4 mg BID.
- Conditions
- Systemic Sclerosis
- Being tested
- treprostinil diethanolamine
- Keywords
- systemic sclerosis, scleroderma, pharmacokinetics, treprostinil diethanolamine
- Medical subject headings
- Scleroderma, Systemic, Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
treprostinil diethanolamineDrug
Cohort 1: Single 1 mg treprostinil diethanolamine sustained release tablet dose
treprostinil diethanolamineDrug
Cohort 2: treprostinil diethanolamine sustained release doses will be escalated up to a target dose of 4 mg BID
| Study group | Role | What they receive |
|---|---|---|
| treprostinil diethanolamine | Experimental | Not described Receives: Drug: treprostinil diethanolamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cohort 1: treprostinil pharmacokinetics in patients with systemic sclerosis following single oral administration of a 1 mg treprostinil diethanolamine SR dose.
Measured: pre-24hrs post dose
Cohort 2: treprostinil pharmacokinetics at dose levels of 2 mg BID and 4 mg BID, respectively, in patients with systemic sclerosis following repeated oral administration of treprostinil diethanolamine SR tablets
Measured: 0-12 hrs post-dose
adverse event monitoring
Measured: Cohort 1:Day 0 to Day 2; Cohort 2: Day 0 to Day 47
Secondary outcomes (2)
clinical laboratories
Measured: Cohort 1: Day 0 and Day 2; Cohort 2: Day 0 and Day 47
Cohort 2: Raynauds Phenomenon Visual Analoge Scale
Measured: 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2009 (estimated)
- Study startDec 2008
- Primary completionJan 2010
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Systemic SclerosisStudies of the same condition, open and under way.
- More trials run by United TherapeuticsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kristan Rollins, PharmD, Study director, United Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00848939
- Sponsor's protocol ID
- TDE-DU-101
- Acronym
- DISTOL-PK
- Status last verified
- Oct 2012
- First submitted
- 19 Feb 2009
- Last updated
- 23 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Shah AA, Schiopu E, Hummers LK, Wade M, Phillips K, Anderson C, Wise R, Boin F, Seibold JR, Wigley F, Rollins KD. Open label study of escalating doses of oral treprostinil diethanolamine in patients with systemic sclerosis and digital ischemia: pharmacokinetics and correlation with digital perfusion. Arthritis Res Ther. 2013 Apr 18;15(2):R54. doi: 10.1186/ar4216.
PubMed 23597147
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Evaluation of the Pharmacokinetics and Safety of Fixed and Escalating Doses of Oral Treprostinil Diethanolamine (UT-15C) Sustained Release Tablets in Patients With Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT00848939
- Acronym / sponsor ID
- DISTOL-PK / TDE-DU-101
- Conditions
- Systemic Sclerosis
- Keywords
- systemic sclerosis, scleroderma, pharmacokinetics, treprostinil diethanolamine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Jan 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 20 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the pharmacokinetic and safety profile of treprostinil following fixed and escalating doses of treprostinil diethanolamine SR tablets. Open-label, two-part study assessing the pharmacokinetics, safety, and tolerability of oral treprostinil diethanolamine SR. Cohort 1: single 1 mg treprostinil diethanolamine SR dose. Cohort 2: escalating doses of treprostinil diethanolamine SR up to a target dose of 4 mg BID.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treprostinil diethanolamine | Experimental | Drug: treprostinil diethanolamine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subject gives voluntary written informed consent to participate in the study.
- Subject has been diagnosed with systemic sclerosis (SSc) as defined by American College of Rheumatology (ACR) criteria.
- Males and females age greater than 18 years at time of Screening.
- Presence of active digital ulcer OR history of digital ulcer occurring within past 6 months at time of Screening and poorly controlled Raynaud's phenomenon (as documented by patient report of 6-10 episodes per week).
- Females of childbearing potential must be willing to use two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at Screening, confirmed at Baseline if separate visits. Women who are surgically sterile or have been post-menopausal for at least 2 years are not considered to be of child-bearing potential.
Key exclusion criteria (20 listed)
- Has diagnosis of pulmonary arterial hypertension and receiving approved or investigational therapies for PAH, including endothelin receptor antagonists, phosphodiesterase inhibitors, or prostacyclin analogues.
- Body weight less than 40 kg at time of Screening, confirmed at Baseline.
- The subject has a history of postural hypotension, unexplained syncope, a blood pressure that is less than 85 mmHg systolic or 50 mmHg diastolic at Screening or Baseline.
- Hemoglobin concentration less than 75% of the lower limit of the normal range at time of Screening.
- AST and/or ALT concentrations greater than 3 times upper limit of normal (ULN) at time of Screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| treprostinil diethanolamineCohort 1: Single 1 mg treprostinil diethanolamine sustained release tablet dose | Drug | treprostinil diethanolamine |
| treprostinil diethanolamineCohort 2: treprostinil diethanolamine sustained release doses will be escalated up to a target dose of 4 mg BID | Drug | treprostinil diethanolamine |
Primary outcome
Cohort 1: treprostinil pharmacokinetics in patients with systemic sclerosis following single oral administration of a 1 mg treprostinil diethanolamine SR dose.
Time frame: pre-24hrs post dose
Cohort 2: treprostinil pharmacokinetics at dose levels of 2 mg BID and 4 mg BID, respectively, in patients with systemic sclerosis following repeated oral administration of treprostinil diethanolamine SR tablets
Time frame: 0-12 hrs post-dose
adverse event monitoring
Time frame: Cohort 1:Day 0 to Day 2; Cohort 2: Day 0 to Day 47
2 secondary outcomes
clinical laboratories
Time frame: Cohort 1: Day 0 and Day 2; Cohort 2: Day 0 and Day 47
Cohort 2: Raynauds Phenomenon Visual Analoge Scale
Time frame: 7 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2012.
- Derived from this study: PubMed 23597147Shah AA, Schiopu E, Hummers LK, Wade M, Phillips K, Anderson C, Wise R, Boin F, Seibold JR, Wigley F, Rollins KD. Open label study of escalating doses of oral treprostinil diethanolamine in patients with systemic sclerosis and digital ischemia: pharmacokinetics and correlation with digital perfusion. Arthritis Res Ther. 2013 Apr 18;15(2):R54. doi: 10.1186/ar4216.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristan Rollins, PharmD study director
United Therapeutics
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing treprostinil diethanolamine in people with Systemic Sclerosis, run by United Therapeutics at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cohort 1: treprostinil pharmacokinetics in patients with systemic sclerosis following single oral administration of a 1 mg treprostinil diethanolamine SR dose. (time frame: pre-24hrs post dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00848939, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2012.