New oral form of nocturia agent found safe, efficacious

February 1, 2011

An investigational formulation of desmopressin demonstrated efficacy in treating nocturia in adults in a randomized, placebo-controlled study.

"Desmopressin appears to be safe and effective, and it is a tool for treatment of patients with nocturia," said first author Jeffrey Weiss, MD, professor and chair of urology at State University of New York Downstate Medical School in Brooklyn.

Dr. Weiss said desmopressin, a synthetic analogue of arginine vasopressin, has a proven track record in managing nocturia, and this particular study investigated the efficacy and tolerability of an orally disintegrating formulation.

Researchers dosed and treated 799 patients who came from 78 study centers in the U.S. A total of 757 patients made up the intent-to-treat population, received one dose or more of the medication, and had one or more post-baseline efficacy observations. A total of 710 subjects completed the first phase of the study, in which they were randomized to placebo or one of four doses of desmopressin: either 10, 25, 50, or 100 mcg, for 28 days, all of which were administered 1 hour before bedtime.

In the second phase of the study, subjects who were already on desmopressin continued their treatment while those who had received placebo or desmopressin, 10 mcg, were randomized to one of the active treatment arms up to month 6. After 6 months, there was an open-label extension study, and investigators gathered data at the 1-year mark.

Dose-response trend noted

The baseline number of voids was 3.3, and there were statistically significant reductions in voids among patients who received the 50- and 100-mcg doses of desmopressin. Investigators observed there was a dose-response trend, with the difference between the placebo and the 50- and 100- mcg doses being significant at day 28 (p<.05). Investigators concluded that the 10-mcg dose was sub-therapeutic.

About 20% of patients were taking concomitant medications for conditions like overactive bladder and BPH, and that population experienced a diminution of nocturia comparable to those patients who were not being treated with concomitant OAB/BPH medications.

Hyponatremia was the only serious adverse event, with cases being reported at higher doses.

"The percentages were quite low for the 50- and 100-mcg arms," Dr. Weiss said. "The good news is that we can minimize the risk of hyponatremia resulting from exposure to desmopressin by insisting their baseline serum sodium be normal prior to therapy. In the elderly in particular, it is important to obtain a serum sodium at day 4, day 8, and day 30. Hyponatremia is quite rare, but it is definitely more common in patients 65 and older."

As result of therapy, many patients experienced at least 4 hours of uninterrupted sleep, noted Dr. Weiss.

"We know degraded sleep has serious effects on quality of life, work-related productivity, and the risk of falls and fractures," he said. "You would assume that improvement of nocturia would improve the quality of life and morbidity and mortality outcomes, but that needs to be verified with longitudinal studies."

The study was funded by Ferring Pharmaceuticals, and Dr. Weiss is a consultant for Ferring, Pfizer, Vantia, Allergan, Astellas, and Watson Pharmaceuticals.