Assess Efficacy of of Oral Treprostinil in Patients With Symptomatic Primary or Secondary Raynaud's Phenomenon

NCT02583789 | Completed Early Phase 1

• 1 other identifier: 2015P001879
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study represents the first trial to assess the efficacy of oral treprostinil therapy in patients with symptomatic primary or secondary Raynaud's Phenomenon (RP) resistant to vasodilatory therapy. The study will be randomized 1:1 UT-15C to placebo. The design is a crossover study and all subjects will be randomized to receive oral treprostinil sustained release tablets or matching placebo for 12 weeks and then crossover for 12 weeks. All subjects will be exposed for 12 weeks of treatment with oral UT-15C during the study.

Conditions

Raynaud's Phenomenon

Outcome Measures

Primary Outcomes (1)

• Change in Raynaud's Condition Score

  Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase

  from baseline (2-week run in) to 6 weeks of treatment

Secondary Outcomes (3)

• Change in number of Raynaud's Phenomenon attacks

  from baseline (2-week run in) to 6 weeks of treatment

• Change in duration of Raynaud's Phenomenon attacks

  from baseline (2-week run in) to 6 weeks of treatment

• Reduction of ulcer burden among secondary Raynaud's Phenomenon patients

  from baseline (2-week run in) to 6 weeks of treatment

Study Arms (2)

oral treprostinil

ACTIVE COMPARATOR

Dosing of oral treprostinil will be initiated at 0.125 mg three times daily. Dose escalations of oral treprostinil can occur every 72 hours (three consecutive doses) in 0.125 mg increments. Subjects will be titrated as tolerated to a goal dose of 2mg TID over a 6-week period.

Drug: oral treprostinil; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Placebo mimics oral treprostinil and will be taken three times a day

Drug: oral treprostinil; Drug: Placebo

Interventions

oral treprostinil DRUG

Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase

Also known as: Orenitram

Placebo; oral treprostinil

Placebo DRUG

Placebo is a sugar pill manufactured to resemble UT-15C. Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase

Also known as: Sugar pill

Placebo; oral treprostinil

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥18-65 years
• Patients with primary Raynaud's Phenomenon
• Patients with Raynaud's secondary to connective tissue diseases (including scleroderma (SSc), limited scleroderma (CREST), mixed connective tissue disease (MCTD), primary Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), with diagnosis of the underlying rheumatic disease based on standard criteria
• Patients on stable dose phosphodiesterase inhibitors (sildenafil, tadalafil or vardenafil), endothelin antagonists, alpha adrenergic antagonists, or calcium channel blockers defined as 3-months with no change in dose will be allowed to participate

You may not qualify if:

• Uncontrolled hypertension, diabetes mellitus, history of orthostatic hypotension, acute coronary or cerebrovascular event within 3 months, evidence of malignancy, history of sympathectomy
• Smoking within 3 months or smoking cessation using nicotine products
• Subjects currently taking or other prostacyclins.
• Pregnant or breast feeding or considering pregnancy in next 4 months
• Participation in trial with an investigational drug within 30 days

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• United Therapeutics: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (3)

• Ennis H, Hughes M, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud's phenomenon. Cochrane Database Syst Rev. 2016 Feb 25;2(2):CD002069. doi: 10.1002/14651858.CD002069.pub5.

  PMID: 26914257 BACKGROUND

• Roustit M, Hellmann M, Cracowski C, Blaise S, Cracowski JL. Sildenafil increases digital skin blood flow during all phases of local cooling in primary Raynaud's phenomenon. Clin Pharmacol Ther. 2012 May;91(5):813-9. doi: 10.1038/clpt.2011.302. Epub 2012 Mar 28.

  PMID: 22453196 BACKGROUND

• Vayssairat M. Controlled multicenter double blind trial of an oral analog of prostacyclin in the treatment of primary Raynaud's phenomenon. French Microcirculation Society Multicentre Group for the Study of Vascular Acrosyndromes. J Rheumatol. 1996 Nov;23(11):1917-20.

  PMID: 8923366 BACKGROUND

MeSH Terms

Conditions

Raynaud Disease

Interventions

treprostinil; Sugars

Condition Hierarchy (Ancestors)

Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• Aaron Waxman, MD/PhD

  Brigham and Womens Hospital

  PRINCIPAL INVESTIGATOR

• Paul Dellaripa, MD

  Brigham and Womens Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 8, 2015
• First Posted: October 22, 2015
• Study Start: May 1, 2016
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: January 10, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)