The U.S. Food and Drug Administration (FDA) has approved Ferring’s Nocdurna (desmopressin acetate) for the treatment of nocturia due to nocturnal polyuria.
Nocturia, the need to awaken at night to pass urine, is a complex medical condition with various contributing factors. The night-time overproduction of urine, nocturnal polyuria, is responsible for nocturia in up to 88% of cases.
Nocdurna, once-daily lyophilisate tablets are administered sublingually in gender-specific low doses, tailored specifically for men (50 mcg) and women (25 mcg).
It has as an active substance desmopressin, a synthetic analog of the naturally occurring vasopressin, an antidiuretic hormone that promotes water absorption by the kidneys. Desmopressin in Nocdurna works by mimicking the effect of vasopressin and binds to specific receptors in the kidneys. This action can prevent the kidneys from filtering excessive amounts of water out of the blood as they make urine, reducing the volume of urine and night-time urination. However, desmopressin, unlike vasopressin, does not affect blood pressure.
Desmopressin has been approved in both adults and children and in multiple strengths, dosage forms and routes of administration worldwide for more than 40 years for several medical conditions, such as for central diabetes insipidus and for primary nocturnal enuresis.
The approval was based on 3 double-blind, placebo-controlled trials and 1 open-label extension trial of up to 3 years in patients ≥18 years old. In clinical trials, nocturnal polyuria was defined as nighttime urine production exceeding one-third of the 24-hour urine production. The efficacy of Nocdurna was established in two 3-month trials; Study 1 enrolled only women while Study 2 enrolled only men.
In Study 1, women (N=237) were randomized to receive either sublingual Nocdurna 27.7mcg or placebo every night approximately 1 hour before bedtime; men (N=230) in Study 2 received either sublingual Nocdurna 55.3mcg or placebo. The co-primary endpoints in both trials were: 1) change in the number of nocturia episodes/night from baseline during the 3-month period and; 2) 33% responder status during 3 months of treatment (a decrease of 33% in the mean number of nocturnal voids compared to baseline).
Results showed an average reduction of nocturnal voids from baseline of -1.5 (difference from placebo -0.3) for women and -1.3 for men (difference from placebo -0.4) with Nocdurna. In addition, 78% of women and 67% of men in the Nocdurna group achieved 33% responder status vs 62% and 50% for placebo, respectively.
Nocdurna carries a Boxed Warning for hyponatremia; the treatment is contraindicated in patients at increased risk of severe hyponatremia, such as those with excessive fluid intake, illnesses that cause fluid or electrolyte imbalances, and in patients using loop diuretics or systemic or inhaled glucocorticoids.
Nocdurna will be available in the second half of 2018 as a sublingual tablet in two dosage strengths: 27.7mcg (for women) and 55.3mcg (for men), both in 30-count cartons. The recommended dose for women is lower as women were more sensitive to the effects of Nocdurna and had a higher risk of hyponatremia with the higher dose in clinical trials.