Pharmacokinetics of Oral Treprostinil in Patients With Systemic Sclerosis

Systemic Sclerosis Clinical Trial

— DISTOL-PK  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00848939
• Other study ID #: TDE-DU-101
• Status: Completed
• Phase: Phase 1
• First received: February 19, 2009
• Last updated: October 19, 2012
• Start date: December 2008
• Est. completion date: April 2010

Study information

• Verified date: October 2012
• Source: United Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: April 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Drug:
• treprostinil diethanolamine
Cohort 1: Single 1 mg treprostinil diethanolamine sustained release tablet dose
• treprostinil diethanolamine
Cohort 2: treprostinil diethanolamine sustained release doses will be escalated up to a target dose of 4 mg BID

Locations

Country	Name	City	State
United States	University of Michigan Scleroderma Program	Ann Arbor	Michigan
United States	Johns Hopkins Scleroderma Center	Baltimore	Maryland
United States	Boston University School of Medicine Rheumatology Arthritis Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort 1: treprostinil pharmacokinetics in patients with systemic sclerosis following single oral administration of a 1 mg treprostinil diethanolamine SR dose.		pre-24hrs post dose	No
Primary	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		0-12 hrs post-dose	No
Primary	adverse event monitoring		Cohort 1:Day 0 to Day 2; Cohort 2: Day 0 to Day 47	Yes
Secondary	clinical laboratories		Cohort 1: Day 0 and Day 2; Cohort 2: Day 0 and Day 47	Yes
Secondary	Cohort 2: Raynauds Phenomenon Visual Analoge Scale		7 weeks	No