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Avadel Pharmaceuticals Announces Journal of Urology Publication of Phase 3 Data on NOCTIVA
“We are extremely pleased that these pivotal results on NOCTIVA were published in the well-respected
Noctiva is a proprietary emulsified formulation of desmopressin that uses a unique permeation enhancer to deliver a microdose of desmopressin. It is the lowest effective dose of desmopressin approved by the
In two double-blind, placebo controlled, Phase 3 trials, DB3 and DB4, 1,333 patients with a mean of 2.16 or more nocturic voids (NOV) per night were randomized to NOCTIVA 1.66 or 0.83 mcg, or placebo, for a 12-week treatment period. Existing etiologies of nocturia included nocturnal polyuria (80 percent), benign prostatic hyperplasia (39 percent), and overactive bladder (27 percent). Co-primary end points were the mean reduction in nocturic episodes per night from baseline and the percent of patients with a 50 percent or greater reduction in mean nocturic episodes per night. Secondary end points were the validated INTU (Impact of Nighttime Urination) questionnaire (in DB4 only), time to first nocturic void, the percent of nights with one or fewer nocturic voids and the reduction in volume of urine produced at night.
The results showed that reduction in mean nocturic episodes per night from baseline were significantly greater with NOCTIVA 0.83 mcg and 1.66 mcg compared to placebo in both DB3 (-1.4 and -1.6 respectively, vs -1.2, placebo) and DB4 (-1.4 and -1.5 respectively, vs -1.2 placebo). The percentage of patients who achieved a 50 percent reduction in mean nocturic episodes per night was significantly higher with the NOCTIVA 1.66 mcg dose compared with placebo in the DB3 (52 percent vs 32.8 percent) and DB4 (46.5 percent vs 28.5 percent) studies, as well as the pooled analysis of both studies (48.7 percent vs 30.3 percent). A significant difference was also observed with the 0.83 mcg dose compared with placebo in the pooled analysis (37.9 percent vs 30.3 percent).
Both doses of NOCTIVA had an acceptable safety profile and were well tolerated. The most common adverse events of nasal discomfort and nasopharyngitis were mild to moderate in intensity and occurred with similar incidence in the placebo group. Incidence of hyponatremia, defined as serum sodium ≤125 mmol/L regardless of symptoms or <130 mmol/L with symptoms, was low and occurred in five patients (1.1 percent) at the higher dose and in one patient (0.2 percent) who received placebo. No patient receiving the 0.83 mcg dose developed hyponatremia.
In secondary endpoints, patients receiving the 1.66 mcg dose had a statistically significant improvement in the overall impact score reported on the INTU (p = 0.0225) indicating better quality of life and a clinically meaningful benefit. These results mark the first time a decrease in nocturic episodes was correlated with improvement in patients’ quality of life in terms of how they feel and function. Compared with placebo in DB3 and DB4 studies and in the pooled analysis, both strengths of NOCTIVA significantly increased the time from bedtime to the first nocturic void. There was also a significant increase in the percent of nights with one or fewer nocturic episodes after treatment with NOCTIVA 1.66 mcg dose compared with placebo; in the pooled analysis both 0.83 mcg and 1.66 mcg doses showed significant improvement compared to placebo.
“We are very pleased that NOCTIVA 1.66 mcg met all co-primary and secondary endpoints in these trials,” said
Nocturia is a highly prevalent, under-recognized condition associated with disrupted sleep, which results in reduced productivity and negatively impacts health and quality of life. 3,,,,,,
NOCTIVA is an emulsified microdose vasopressin analog, approved by the
See full prescribing information for complete boxed warning.
Important Safety Information for NOCTIVA (desmopressin acetate)
- NOCTIVA can cause hyponatremia, which may be life-threatening if severe.
- NOCTIVA is contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive fluid intake, illnesses that can cause fluid or electrolyte imbalances, and in those using loop diuretics or systemic or inhaled glucocorticoids.
- Ensure serum sodium is normal before starting or resuming NOCTIVA. Measure serum sodium within seven days and approximately one month after initiating therapy or increasing the dose, and periodically during treatment. More frequently monitor serum sodium in patients 65 years of age and older and in patients at increased risk of hyponatremia.
- If hyponatremia occurs, NOCTIVA may need to be temporarily or permanently discontinued.
INDICATIONS AND USAGE
NOCTIVA is a vasopressin analog indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void.
Limitation of Use: Not studied in patients younger than 50 years of age.
- Hyponatremia or a history of hyponatremia
- Primary nocturnal enuresis
- Concomitant use with loop diuretics or systemic or inhaled glucocorticoids
- Estimated glomerular filtration rate below 50 mL/min/1.73 m2
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- During illnesses that can cause fluid or electrolyte imbalance
New York Heart Association(NYHA) Class II-IV congestive heart failure
- Uncontrolled hypertension
WARNINGS AND PRECAUTIONS
- Fluid retention: Not recommended in patients at risk of increased intracranial pressure or history of urinary retention. Monitor volume status in patients with NYHA Class I congestive heart failure.
- Nasal conditions: Discontinue in patients with concurrent nasal conditions that may increase absorption, until resolved.
Common adverse reactions in clinical trials (incidence >2%) included nasal discomfort, nasopharyngitis, nasal congestion, sneezing, hypertension / blood pressure increased, back pain, epistaxis, bronchitis and dizziness.
Monitor serum sodium more frequently when NOCTIVA is concomitantly used with drugs that may cause water retention and increase the risk for hyponatremia (e.g., tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, nonsteroidal anti-inflammatories, lamotrigine and carbamazepine).
USE IN SPECIFIC POPULATIONS
- Pregnancy: Use of NOCTIVA is not recommended.
- Pediatric: Do not use NOCTIVA for primary nocturnal enuresis in children.
To report SUSPECTED ADVERSE REACTIONS, contact Avadel at 1-877-638-4579 or
Please see the full Prescribing Information for NOCTIVATM at www.Noctiva.com/prescribing-information.
Avadel Sr. Director, Investor Relations and Corporate Communications
Phone: (636) 449-5866
Phone: (202) 591-4045
1 Bosch JLH, Weiss JP. The prevalence and causes of nocturia. J Urol. 2010; 184(2):440-446.
2 Ancoli-Israel S, Bliwise DL, Nørgaard JP. The effect of nocturia on sleep. Sleep Med Rev. 2011 April; 15(2): 91-97.
3 Bliwise DL, et al. Sleep Med. 2009;10(5):540-548.
4 Coyne KS, et al. BJU Int. 2003;92(9):948-954.
5 Holm-Larsen T. Neurourol Urodyn. 2014;33(Suppl 1):S10-14.
6 Kobelt G, et al. BJU Int. 2003;91(3):190-195.
7 Tikkinen KA, et al. Eur Urol. 2010;57(3):488-496.
8 Weiss JP. Rev Urol. 2012;14(3-4):48-55.
9 Abrams P. European Urology Supplements. 2005;3:6(1-7).