Efficacy and Safety of Vascana® in Subjects With Secondary Raynaud's Phenomenon

Inclusion Criteria:

1. Provide written consent prior to any study-specific evaluation
2. Males and females aged 18 years to 75 years, inclusive
3. A clinical diagnosis of secondary Raynaud's Phenomenon (defined as Raynaud'sPhenomenon (RP) significant enough to cause a patient to modify daily behavior) asdetermined by a history of cold sensitivity with pain, numbness, and/or tingling alongwith pallor or cyanosis of the fingers, or by such an event observed by the studyphysician and a diagnosis of a disease state known to be associated with RP. SecondaryRP may be due to scleroderma, systemic lupus erythematosus, mixed connective tissuedisease, or other connective tissue diseases
4. Agree to apply the study drug to their fingers as specified in the protocol
5. Agree to the controlled cold exposures as described in the protocol
6. Willing to discontinue current vasodilator therapies used specifically for thetreatment of Raynaud's
7. Agree not to use any other investigational medications or approved or unapprovedtherapies to treat RP and its symptoms while participating in this study. Suchmedications include, but are not limited to: other dosages forms of nitroglycerin, eg,isosorbide dinitrate, fenoldopam mesylate, milrinone lactate, nifedipine, diltiazem,felodipine, nimodipine, nisoldipine, fluoxetine, pregabalin, and verapamil. Use ofphosphodiesterase 5 inhibitors (eg, sildenafil, tadalafil, vardenafil) is excludedunless being used intermittently for male erectile dysfunction and not taken within 48hours of scheduled study drug dosing
8. Negative urine pregnancy test for women of child-bearing potential prior to the firststudy treatment and who agree to use effective contraception throughout the study
9. Able to comply with all study requirements

Exclusion Criteria:

1. Past history of RP attacks of sufficient severity as to require inpatienthospitalization
2. Presence of an active digital ulcer defined as a painful ulcer with visible depth andloss of epithelialization. Ulcers covered with eschar wherein depth andepithelialization cannot be judged are said to be "indeterminant" and are notexclusionary.
3. Raynaud's Phenomenon secondary to non-connective tissue disorders includingthromboangiitis obliterans (Buerger's disease), hemorheologic disorders, majorarterial occlusive disease, past exposure to vasopathic agents (including vinblastine,cis platinum, and bleomycin), ongoing therapy with vasoconstrictive agents (eg,beta-blockers), and past frostbite injury amongst others. Subjects with hepatitis Cshould also be excluded.
4. Patients diagnosed with pulmonary arterial hypertension requiring specific therapy.
5. Concurrently using any nitrate medication or medications known to interact withnitroglycerin such as sildenafil, and other treatments for erectile dysfunction beyondscreening. Subjects may participate in the study once these drugs have beendiscontinued for at least 5 half-lives
6. Concurrently using any medication or device which might interfere with the studymedication (including RP therapies, drugs used for hypertension, arrhythmia,depression, and pain), specifically calcium channel blockers and the compounds listedin prohibited concomitant medications beyond screening, unless such medication isrequired for a condition other than Raynaud's. Subjects may participate in the studyonce these drugs have been discontinued for at least 5 half-lives.
7. Known allergy to nitroglycerin or common topical cream ingredients
8. History of migraine, cluster, or vascular headaches, or chronic pain (defined as painof 3-hour duration or longer on a daily basis) with greater intensity than the painassociated with RP or other chronic pain condition in their fingers
9. Any unstable medical problem or any current medical condition that, in the judgment ofthe investigator, would contraindicate the administration of the study medication,interfere with the study evaluations, or interfere with the subject's ability tocomply with the study protocol
10. Cognitive or language difficulties that would impair completion of the symptomassessment instruments
11. Within the past 3 months, have had a myocardial infarction, uncontrolled congestiveheart failure, unstable angina, uncontrolled hypotension, or uncontrolled hypertension (defined as subjects not being treated medically to control these conditions)
12. Participated in a study of any investigational drug within 4 weeks prior to visit 1
13. Screening laboratory values are 20% or more from the upper or lower limit of normaland that are considered to be clinically significant to the investigator
14. Had major abdominal, thoracic, or vascular surgery within 6 months of visit 1
15. Pregnant or nursing women
16. Women of childbearing potential who are unable or unwilling to comply with thecontraceptive requirements during the study period
17. History of relevant drug and/or food allergies that resulted in a systemic reactionthat required medical treatment
18. History of alcohol abuse or drug addiction which in the estimation of the principalinvestigator would affect the subjects ability to participate in the study
19. Consumption of alcohol on day before a visit and day of the visit.
20. Consumption of two or more alcoholic beverages on a daily basis.
21. Use of tobacco products of any type and at any level in the preceding 6 months and forthe duration of the study.