A Safety and Efficacy Study of 552-02 in Subjects With Dry Mouth Associated With Sjogren's Syndrome

The primary objective of this clinical study is to determine whether daily administration of an oromucosal formulation of 552-02 improves the global assessment of dry mouth, as assessed by visual analog scale (VAS), in subjects with primary Sjögren's syndrome.

The secondary objectives of this study are as follows:

• To evaluate the safety of daily administration of an oromucosal formulation of 552-02 in subjects with primary Sjögren's syndrome.
• To evaluate whether administration of an oromucosal formulation of 552-02 improves the subjective measurement of 6 different salivary functions, as measured using VAS, in subjects with primary Sjögren's syndrome.

Inclusion criteria

• Male or female, aged 18 to 80 years (inclusive), and capable of providing their written informed consent.
• Male subjects must be either not sexually active, surgically sterilized, or agree to use an appropriate "double-barrier" method during study participation and for at least 30 days after the completion of dosing.
• Non-pregnant female subjects must be either not sexually active, post-menopausal, surgically sterilized; or agree to use an appropriate "double-barrier" method; or are currently using a prescribed transdermal, injection, implant, or oral contraceptive for at least 30 days before study participation and at least 30 days after the completion of dosing.
• Good health, as determined by a medical history, a physical examination, a detailed oral examination, 12-lead ECG, and measurement of clinical chemistry, hematology, urinalysis, and serology data.
• Demonstrated minimal level of unstimulated whole mouth salivary flow (greater than or equal to 0.05 milliliters [ie, 0.05 grams] per 5 minutes).
• Demonstrated clinically significant, moderate to severe level of dry mouth at screening as determined by his/her score on a 100-mm global VAS of dry mouth symptoms with anchors ranging from 'not dry at all' (0) to 'dry as a desert' (100) as follows:
• Minimal VAS score of 50 mm at Visit 1.
• Diagnosis of primary Sjögren's syndrome.

Exclusion criteria

• Currently using a potassium-sparing diuretic antihypertensive drug that contains amiloride; spironolactone (e.g.,Aldactone, Novo-Spiroton, Spiractin, Spirtone, Verospiron or Berlactone); triamterene (e.g., Dyrenium); or plerenone (e.g., Inspra). Chronic use antihistamines will be permitted if started at least 30 days before Visit 1, and a stable dose is maintained throughout the trial.
• Started using systemic cholinergic secretagogues or tricyclic antidepressant drugs within 12 weeks before screening, is not on a stable dosing regimen for at least 14 days prior to the Screening visit, or who is unable to maintain stable dosing throughout the study.
• Unable to withhold the use of oral comfort agents (eg, Oasis, MouthKote, etc) following enrollment in the study (Visit 1).
• Shows evidence of a significant active or ongoing oral infection or other oral conditions (eg, lichen planus) that, in the opinion of the Investigator, might affect the safety of the subject or be exacerbated during study participation.
• Acutely infected salivary glands or suspected closure of the salivary glands.
• A condition that may confound the diagnosis of primary Sjögren's syndrome.
• Received an investigational drug within the past 30 days.
• Received 552-02 in a previous study.
• History of multiple drug allergies or allergy to any medicine chemically related to the study drug (eg, amiloride, Moduretic, Midamor, triamterene).
• Any clinically significant allergic disease, including food allergies, with the exception of nonactive hayfever.
• Present history of any clinically significant and uncontrolled neurologic, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, or hematological disorder or disease, or any other major disorder or disease, in the opinion of the Investigator.
• Sitting blood pressure at screening higher than 150/90 mmHg or lower than 100/50 mmHg after resting for 5 minutes.
• Sitting pulse rate at screening outside the range of 50 - 90 beats per minute (bpm) after resting for 5 minutes.
• Consumes more than 2 alcoholic drinks per day or has a significant history of alcoholism or drug/chemical abuse within the past 12 months.
• History of using tobacco products within the last 3 months.
• Has viral hepatitis or tests positively for the hepatitis B surface antigen (HBsAg) or hepatitis C (non-A, non-B) antibody, or a positive result for human immunodeficiency virus (HIV) antibodies.
• Positive serum pregnancy test or is nursing (female subjects only).