Analyses with patients stratified into three groups by age showed that an emulsified microdose desmopressin acetate nasal spray (Noctiva) consistently extended the first uninterrupted sleep period in a clinically meaningful manner for patients of all ages.
Efficacy outcomes and adverse-event data from two phase III pivotal trials supported the FDA decision to approve AV-002, an emulsified microdose desmopressin acetate nasal spray (Noctiva), as the first treatment for nocturia due to nocturnal polyuria in adults who awaken at least two times per night to void.
Speaking at the AUA annual meeting in San Francisco, Benjamin M. Brucker, MD, of New York University Langone Health, New York, reported new analyses demonstrating that the benefits and safety of AV-002 treatment are the same in elderly patients compared with the overall enrolled population that included adults aged ≥50 years.
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Analyses with patients stratified into three groups by age (≥50, ≥65, and ≥75 years) showed that AV-002 consistently extended the first uninterrupted sleep period in a clinically meaningful manner for patients of all ages. The percentage of patients experiencing one or fewer nocturic voids per night also increased consistently in all age groups. The safety review showed there were no cases of severe hyponatremia among patients ≥65 years treated with AV-002, 0.83 mcg, which is the recommended starting dose for this older age group.
“Nocturia is a condition that affects people of all ages and has many negative consequences, but previously available desmopressin preparations did not work as well in older patients and had a poorer safety profile,” Dr. Brucker told Urology Times.
Next -Dr. Brucker: Data "give me confidence to talk to older patients about nocturia knowing that I can now offer them safe and effective therapy"“AV-002 has been engineered to provide immediate onset of action and a predictable duration using the lowest effective dose to mitigate the risk of hyponatremia. The findings from the age-based analyses of the phase III study data give me confidence to talk to older patients about nocturia knowing that I can now offer them safe and effective therapy," Dr. Brucker said.
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He added that data collected in the phase III studies also showed that treatment with AV-002 was associated with statistically significant improvements in quality of life and patient-reported impact of nocturia outcomes in the overall population.
“The data from these questionnaires are now being analyzed with patients stratified by age, and I have no doubt that the results will show consistent benefits in the older age group,” Dr. Brucker told Urology Times.
To be eligible for participation in the AV-002 phase III studies, patients had to be ≥50 years of age and have a history of ≥2 nocturic voids per night for 6 months. In total, 1,333 patients were randomized into three treatment arms to receive AV-002, 0.83 mcg; AV-002, 1.66 mcg; or placebo nightly for 12 weeks. The overall population included 727 patients aged ≥65 years and 292 patients aged ≥75 years.
The mean first uninterrupted sleep period across all treatment arms in all age groups was 2.4 to 2.5 hours at baseline and was consistently extended at the end of the study by 1.3 to 1.7 hours with either dose of AV-002 in all age groups.
“The first uninterrupted sleep period is a critically important measure when talking about nocturia because it is during the first 3 to 4 hours of sleep when patients get the deep, slow-wave restorative sleep that is critical for good daytime function and productivity,” said Dr. Brucker.
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“Patients of all ages were reaching this threshold after starting treatment with either dose of AV-002.”
Continue to the next page for more data.Analyses of data on nights with ≤1 nocturic void showed a dose-related benefit of AV-002, but with either dose of AV-002 across all age groups, patients experienced statistically significant increases from baseline in the percentage of nights with ≤1 nocturic void.
“Overall, patients treated with AV-002 experienced nearly 50% of nights with ≤1 nocturic void,” Dr. Brucker said.
“Increased nocturia correlates with increased degree of bother and difficulty sleeping, and that is why it is important to look at nocturic void episodes. Getting up no more than once during the night to void is usually not impactful on daytime function and quality of life.”
Severe hyponatremia, defined as serum sodium <125 mEq/L, occurred in five patients (1.1%) aged ≥65 years. All of the five patients were in the AV-002, 1.66 mcg treatment arm and four were on corticosteroid therapy that may have contributed to the hyponatremia, Dr. Brucker said.
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Sixteen patients aged ≥65 years (3.2%) developed moderate hyponatremia (serum sodium, 126 mEq/L-129 mEq/L), including seven patients (2.8%) treated with AV-002, 0.83 mcg. All cases of moderate hyponatremia were discovered on routine laboratory testing and none were symptomatic.
Dr. Brucker noted that none of the patients enrolled in the pivotal trials had specific dietary or fluid modifications suggested to them and that patients with concomitant overactive bladder (OAB) or BPH were not excluded from participation.
“The pivotal trials do not give guidance on how to sequence AV-002 for the management of patients with BPH or OAB who are suffering from nocturia. However, I see no reason not to use AV-002 in these patients to address any problem they are having with overproduction of urine at night,” he told Urology Times.
Dr. Brucker is an adviser to and speaker for Avadel Pharmaceuticals, which provided funding for the study. One of Dr. Brucker’s co-authors is an investigator for Allergan.
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