18457 An Evaluation of Treatment Effect in Responder

18457 An Evaluation of Treatment Effect in Responder and Nonresponder Patients With Nocturia Receiving SER 120 Nasal Spray in 2 Phase 3 Clinical Studies Roger Dmochowski, 1 Alan Wein, 2 Linda Cheng, 3 Maria Cheng, 3 Steven Abrams, 4 Samuel Herschkowitz, 3 Seymour Fein 3 INTRODUCTION ● SER 120 is a novel, low-dose desmopressin nasal spray formulation designed to achieve low plasma concentrations which limit the anti-diuretic effect to the hours of sleep, thereby minimizing the risk of hyponatremia ● SER 120 is in clinical development for the treatment of patients with nocturia. Two phase 3 studies were conducted to evaluate its efficacy and safety OBJECTIVE ● To evaluate the treatment effect between responder and nonresponder patients with Figure 4. Change in Percent of Nights (on Per-patient Basis) With 0 Nocturic Voids (DB 3 and DB 4) 100 80 DB 3 60 40 20 nocturia receiving SER 120 nasal spray at 1. 5 mcg or 0. 75 mcg dose in 2 phase 3 studies 0 77 n= ● ● NCT 01900704) were similar Eligible patients at least aged 50 years with a history of 2 or more nocturic voids per night were randomized to one of the SER 120 groups or placebo for a 12 -week treatment period Patients completed 3 -day voiding diaries weekly during screening and periodically postrandomization In the DB 4 study, patients also completed an Impact of Nighttime Urination (INTU) questionnaire corresponding to each voiding diary completed during screening and at weeks 6 and 12. The INTU questionnaire consisted of 10 questions categorized into daytime and nighttime domains 1; a reduction in score corresponds to improvement in quality of life Treatment responders were defined as patients with ≥ 50% reduction in nocturic voids between screening and the treatment period for each study The treatment effect for each study was assessed for: – Reduction in nocturic voids (primary endpoint), reduction from baseline in INTU total and nighttime domain scores in the DB 4 study, time from bedtime to first nocturic void, change in the percentage of nights on a per-patient basis with 0 or ≤ 1 nocturic episodes, and reduction in nocturnal urine volume DB 4 N 1. 5 179 93 (52. 0) 86 (48. 0) 260 121 (46. 5) 139 (53. 5) 0. 75 186 77 (41. 4) 109 (58. 6) 262 93 (35. 5) 169 (64. 5) Nonresponders, n (%) N Responders, n (%) Nonresponders, (n %) ● The treatment effect for the primary and secondary endpoints is illustrated in Figures 1 to 6 Figure 1. Reduction in Mean Nocturic Episodes (DB 3 and DB 4) Mean Nocturic Episodes 0. 75 mcg Responders 93 121 0. 75 mcg Nonresponders 109 1. 5 mcg Nonresponders 86 169 139 -0, 5 60 40 0 -1, 5 DB 3 -2, 0 DB 4 -2, 5 77 93 0. 75 mcg Responders n= 84 93 0. 75 mcg Responders 121 1. 5 mcg Responders 109 169 0. 75 mcg Nonresponders 86 139 1. 5 mcg Nonresponders Data are reported as LS mean ± SE 0. 75 mcg Responders 0 -50 -100 -150 -200 -250 -300 -350 -400 -450 n= 74 84 1. 5 mcg Responders 80 82 113 0. 75 mcg Nonresponders 92 156 1. 5 mcg Nonresponders 74 116 DB 3 DB 4 Data are reported as LS mean ± SE ● The pooled analysis of the DB 3 and DB 4 studies showed a low incidence of patients with sodium levels ≤ 129 mmol/L (Table 2) Table 2. Nadir Serum Sodium Levels Postbaseline in Pooled DB 3 and DB 4 Studies (Safety Population) SER 120 1. 5 mcg (n=448) SER 120 0. 75 mcg (n=454) Placebo (n=454) 130– 134 50 (11. 2) 38 (8. 4) 20 (4. 4) 126– 129 9 (2. 0) 0 (0) ≤ 125 5 (1. 1) 0 (0) 1 (0. 2) Interpretation of Results ● SER 120 showed a dose response with a higher percentage of responders at the 1. 5 mcg dose in both studies Figure 2. Reduction in INTU Mean Total and Nighttime Domain Scores (DB 4) 1. 5 mcg Responders 119 0. 75 mcg Nonresponders 124 163 ● Efficacy endpoints including the INTU questionnaire showed substantial incremental improvements for the responders compared with the nonresponders ● Among responding patients, both doses of SER 120 (1. 5 mcg and 0. 75 mcg) showed similar improvement 124 CONCLUSIONS -5 Score n= Serum sodium range, mmol/L, n (%) -1, 0 Data are reported as LS mean ± SE ● SER 120 decreased the number of nocturic episodes and prolonged -10 the first period of sleep in responding patients -15 ● Responding patients reported an improvement in nocturic -20 symptoms using a validated 1 quality-of-life questionnaire on the impact of nighttime urination (INTU) ● SER 120 at doses of 1. 5 mcg and 0. 75 mcg had an acceptable safety profile, and was well tolerated and effective for the treatment of nocturia in adult patients Total Score -25 -30 Data are reported as LS mean ± SE Figure 3. Time From Bedtime to First Void (Posttreatment) (DB 3 and DB 4) 6 REFERENCES DB 3 DB 4 5 Time (h) DB 3 DB 4 20 Volume (m. L) DB 3 Responders, n (%) 0 139 80 Table 1. Number (Percentage) of Treatment Responders and Treatment Nonresponders (DB 3 and DB 4) 0, 0 86 169 100 DB 4 studies are shown in Table 1 77 109 0. 75 mcg 1. 5 mcg Nonresponders Figure 5. Change in Percent of Nights (on Per-patient Basis) With ≤ 1 Nocturic Voids (DB 3 and DB 4) ● The percentage of treatment responders and treatment nonresponders in the DB 3 and n= 121 Figure 6. Change in Nocturnal Urine Volume (DB 3 and DB 4) RESULTS SER 120 Dose (mcg) 93 1. 5 mcg Responders Data are reported as LS mean ± SE % of Nights ● The study designs of the 2 phase 3 studies (DB 3 and DB 4; NCT 01357356 and 93 0. 75 mcg Responders STUDY DESIGN ● Scan to obtain PDF of poster University, Nashville, TN, USA; 2 University of Pennsylvania, Philadelphia, PA, USA; 3 Serenity Pharmaceuticals, LLC, Milford, PA, USA; 4 Allergan plc, Irvine, CA, USA % of Nights 1 Vanderbilt 4 1. Psychometric Evaluation Report of the Questionnaire on the Impact of Nighttime Urination (INTU). Adelphi Values prepared for Allergan plc. , March 2015. DISCLOSURES This study was sponsored by Serenity Pharmaceuticals, LLC, Milford, PA, USA, and Allergan plc, Dublin, Ireland. Writing and editorial assistance was provided to the authors by Meryl Mandle of Evidence Scientific Solutions, Philadelphia, PA, USA, and funded by Allergan plc, Dublin, Ireland. All authors met the ICMJE authorship criteria. Neither honoraria nor payments were made for authorship. 3 2 Financial arrangements of the authors with companies whose products may be related to the present report are listed below, as declared by the authors. RD has served as a consultant/advisor to Allergan plc, Ferring, and Merck; and as a study investigator for Allergan plc. AW has served as a consultant to Allergan plc, Serenity Pharmaceuticals, LLC, Medtronic, and Axonics. LC, MC, SH, and SF are employees of Serenity Pharmaceuticals, LLC. SA is an employee of Allergan plc. 1 0 n= 77 93 0. 75 mcg Responders Data are reported as LS mean ± SE 93 121 1. 5 mcg Responders 109 169 0. 75 mcg Nonresponders 86 139 1. 5 mcg Nonresponders To obtain a PDF of this poster: Scan the QR code OR Visit www. allergancongressposters. com/614143 Charges may apply. No personal information is stored. Presented at the International Continence Society (ICS) 2016 Annual Meeting, 13– 16 September 2016, Tokyo, Japan