Pharmacokinetics of Oral Treprostinil in Patients With Systemic Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00848939
• Date of registration: 19/02/2009
• Prospective Registration: No
• Primary sponsor: United Therapeutics
• Public title: Pharmacokinetics of Oral Treprostinil in Patients With Systemic Sclerosis DISTOL-PK
• Scientific 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
• Date of first enrolment: December 2008
• Target sample size: 28
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00848939
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Kristan Rollins, PharmD
• Affiliation: United Therapeutics

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

- 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Systemic Sclerosis

Intervention(s)

Drug: treprostinil diethanolamine

Primary Outcome(s)

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]

adverse event monitoring [Time Frame: Cohort 1:Day 0 to Day 2; Cohort 2: Day 0 to Day 47]

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]

Secondary Outcome(s)

Cohort 2: Raynauds Phenomenon Visual Analoge Scale [Time Frame: 7 weeks]

clinical laboratories [Time Frame: Cohort 1: Day 0 and Day 2; Cohort 2: Day 0 and Day 47]

Secondary ID(s)

TDE-DU-101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors