CLINICAL STUDIES

Clini cal Studies Head & Neck Cancer Patients A 12 week randomized, double-blind, placebo-controlled study in 207 patients (142 men, 65 women) was conducted in patients whose mean age was 58.5 years with a range of 19 to 77; the racial distribution was Caucasian 95%, Black 4%, and other 1%.

In this population, a statistically significant improvement in mouth dryness occurred in the 5 and 10 mg pilocarpine hydrochloride tablet treated patients compared to placebo treated patients.

The 5 and 10 mg treated patients could not be distinguished.

(See Pharmacodynamics section for flow study details.) Another 12 week, double-blind, randomized, placebo-controlled study was conducted in 162 patients whose mean age was 57.8 years with a range of 27 to 80; the racial distribution was Caucasian 88%, Black 10%, and other 2%.

The effects of placebo were compared to 2.5 mg three times a day of pilocarpine hydrochloride tablets for 4 weeks followed by adjustment to 5 mg three times a day and 10 mg three times a day.

Lowering of the dose was necessary because of adverse events in 3 of 67 patients treated with 5 mg of pilocarpine hydrochloride tablets and in 7 of 66 patients treated with 10 mg of pilocarpine hydrochloride tablets.

After 4 weeks of treatment, 2.5 mg of pilocarpine hydrochloride tablets three times a day was comparable to placebo in relieving dryness.

In patients treated with 5 mg and 10 mg of pilocarpine hydrochloride tablets, the greatest improvement in dryness was noted in patients with no measurable salivary flow at baseline.

In both studies, some patients noted improvement in the global assessment of their dry mouth, speaking without liquids, and a reduced need for supplemental oral comfort agents.

In the two placebo-controlled clinical trials, the most common adverse events related to drug, and increasing in rate as dose increases, were sweating, nausea, rhinitis, diarrhea, chills, flushing, urinary frequency, dizziness, and asthenia.

The most common adverse experience causing withdrawal from treatment was sweating (5 mg t.i.d.

≤1%; 10 mg t.i.d.

=12%).

Sjogren’s Syndrome Patients Two separate studies were conducted in patients with primary or secondary Sjogren’s Syndrome.

In both studies, the majority of patients best fit the European criteria for having primary Sjogren’s Syndrome.

[“Criteria for the Classification of Sjogren’s Syndrome” (Vitali C, Bombardieri S, Moutsopoulos HM, et al: Preliminary criteria for the classification of Sjogren’s syndrome.

Arthritis Rheum 36:340-347, 1993.)] A twelve week, randomized, double-blind, parallel-group, placebo-controlled study was conducted in 256 patients (14 men, 242 women) whose mean age was 57 years with a range of 24 to 85 years.

The racial distribution was as follows: Caucasian 91%, Black 6%, and other 3%.

The effects of placebo were compared with those of pilocarpine hydrochloride tablets 5 mg four times a day (20 mg/day) for 6 weeks.

At 6 weeks, the patients’ dosage was increased from 5 mg pilocarpine hydrochloride tablets q.i.d.

to 7.5 mg q.i.d.

The data collected during the first 6 weeks of the trial were evaluated for safety and efficacy, and the data of the second 6 weeks of the trial were used to provide additional evidence of safety.

After 6 weeks of treatment, statistically significant global improvement of dry mouth was observed compared to placebo.

“Global improvement” is defined as a score of 55 mm or more on a 100 mm visual analogue scale in response to the question, “Please rate your present condition of dry mouth (xerostomia) compared with your condition at the start of this study.

Consider the changes to your dry mouth and other symptoms related to your dry mouth that have occurred since you have taken this medication.” Patients’ assessments of specific dry mouth symptoms such as severity of dry mouth, mouth discomfort, ability to speak without water, ability to sleep without drinking water, ability to swallow food without drinking, and a decreased use of saliva substitutes were found to be consistent with the significant global improvement described.

Another 12 week randomized, double-blind, parallel-group, placebo-controlled study was conducted in 373 patients (16 men, 357 women) whose mean age was 55 years with a range of 21 to 84.

The racial distribution was Caucasian 80%, Oriental 14%, Black 2%, and 4% of other origin.

The treatment groups were 2.5 mg pilocarpine tablets, 5 mg pilocarpine hydrochloride tablets, and placebo.

All treatments were administered on a four times a day regimen.

After 12 weeks of treatment, statistically significant global improvement of dry mouth was observed at a dose of 5 mg compared with placebo.

The 2.5 mg (10mg/day) group was not significantly different than placebo.

However, a subgroup of patients with rheumatoid arthritis tended to improve in global assessments at both the 2.5 mg q.i.d.

(9 patients) and 5 mg q.i.d.

(16 patients) dose (10-20 mg/day).

The clinical significance of this finding is unknown.

Patients’ assessments of specific dry mouth symptoms such as severity of dry mouth, mouth discomfort, ability to sleep without drinking water, and decreased use of saliva substitutes were also found to be consistent with the significant global improvement described when measured after 6 weeks and 12 weeks of pilocarpine hydrochloride tablets use.