A Randomized, Double Blind, Placebo Controlled, Parallel Group, Multi-Center Study With a Double Blind Extension Investigating the Efficacy and Safety of a Fast- Dissolving ("Melt") Formulation of Desmopressin for the Treatment of Nocturia in Adults
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 799
- 试验地点
- 72
- 主要终点
- Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4
研究概览
简要总结
The purpose of this study is to investigate the efficacy and safety of several doses of the melt formulation of desmopressin in a broad population of adult patients with nocturia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Clinical suspicion of bladder outlet obstruction and/or urine flow < 5 ml/s. If medical history and/or physical examination suggest bladder outlet obstruction, uroflowmetry should be performed to confirm the diagnosis
- •Surgical treatment for bladder outlet obstruction/benign prostatic hyperplasia performed within the past 6 months
- •Pregnancy. Females of reproductive age must have documentation of a reliable method of contraception.
- •Use of pessary for pelvic prolapse.
- •Unexplained pelvic mass.
- •Males and Females:
- •Clinical suspicion of urinary retention and/or post void residual volume > 150 ml. If medical history and/or physical examination suggest urinary retention, bladder ultrasound or catheterization should be performed to confirm the diagnosis.
- •Current or past urologic malignancy (e.g., bladder cancer, prostate cancer).
- •Clinical evidence of current genitourinary tract pathology that could interfere with voiding.
- •History of neurogenic detrusor activity (previously known as detrusor hyperreflexia).
- •Suspicion or evidence of cardiac failure.
- •Uncontrolled hypertension.
- •Uncontrolled diabetes mellitus.
- •Renal insufficiency. Serum creatinine must be within normal limits and estimated glomerular filtration rate (eGFR) >=60 mL/min.
- •Active hepatic and/or biliary disease. Aspartate transaminase (AST) or alanine transaminase (ALT) should not be >2 times the upper limit of normal. Total bilirubin should not be > 1.5 mg/dL.
- •Hyponatremia. Serum sodium level must be within normal limits
- •Syndrome of Inappropriate antidiuretic hormone secretion (SIADH).
- •Diabetes insipidus (urine output > 40 ml/kg over 24 hours) as determined by the 3-day voiding diary.
- •Psychogenic or habitual polydipsia
- •Obstructive sleep apnea
- •Known alcohol or substance abuse
- •Work or lifestyle potentially interfering with regular nighttime sleep (e.g., shift workers)
- •Previous desmopressin treatment for nocturia.
- •Any other medical condition, laboratory abnormality, psychiatric condition, mental incapacity or language barrier that, in the judgment of the investigator, could impair patient participation in the trial.
- •Use of loop diuretics (furosemide, torsemide, ethacrynic acid). Other classes of diuretics (thiazides, triamterene, chlorthalidone, amiloride, indapamide) were permitted, either as monotherapy or combination therapy. Subjects using a diuretic were to be encouraged to take it in the morning, if medically feasible.
- •Use of any other investigational drug within 30 days of screening.
- •Concomitant Medications
- •The following medications are permitted provided that the subject has been on a stable dose for the 3 months prior to the screening date (i.e. treatment has not been initiated or discontinued and there has been no change in dose):
- •Alpha-blockers: Cardura (doxazosin); Flomax (tamsulosin); Hytrin (terazosin); Uroxatral (alfuzosin)
- •5 alpha-reductase inhibitors: Avodart (dutasteride); Proscar (finasteride)
- •Antispasmodic, anticholinergic, antimuscarinic therapy for overactive bladder: Detrol, Detrol LA (tolterodine); Ditropan, Ditropan XL (oxybutynin); Enablex (darifenacin); Levsin(hyoscyamine); Oxytrol transdermal (oxybutynin); Sanctura (trospium); Vesicare (solifenacin)
- •Sedative/hypnotic medications for sleep disorders
- •Selective serotonin and mixed norepinephrine/serotonin reuptake inhibitors: Celexa (citalopram); Cymbalta (duloxetine); Effexor (venlafaxine); Lexapro (escitalopram); Paxil(paroxetine); Prozac (fluoxetine); Zoloft (sertraline)
- •Chronic use of nonsteroidal anti-inflammatory agents
- •Diabinese (chlorpropamide)
- •Carbamazepine (carbatrol/tegretol)
- •Amiodarone
研究组 & 干预措施
Placebo
Participants took a placebo 'melt' for 28 days to complete part 1 of the study. In part 2, placebo patients were randomized to one of the other 4 treatment arms based on assignments predetermined at the initial randomization, to receive active desmopressin melt for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).
干预措施: Placebo (Drug)
desmopressin melt 10 μg
Participants took desmopressin melt 10 μg for 28 days to complete part 1 of the study. Participants continued on this dose in part 2 of the study for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).
干预措施: desmopressin acetate (Drug)
desmopressin melt 25 μg
Participants took desmopressin melt 25 μg for 28 days to complete part 1 of the study. Participants continued on this dose in part 2 of the study for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).
干预措施: desmopressin acetate (Drug)
desmopressin melt 50 μg
Participants took desmopressin melt 50 μg for 28 days to complete part 1 of the study. Participants continued on this dose in part 2 of the study for between 1 and 6 months (until the database for part 1 was locked and treatment was unblinded).
干预措施: desmopressin acetate (Drug)
desmopressin melt 100 μg
Participants will take desmopressin melt 100 μg for 28 days to complete part 1 of the study. Participants will continue on this dose in part 2 of the study for between 1-6 months (until the database for part 1 is locked and treatment is unblinded).
干预措施: desmopressin acetate (Drug)
结局指标
主要结局
Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4
时间窗: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
Percentage of participants in each treatment arm that had a greater than 33% reduction from baseline to the end of Part I (week 4) in mean number of nocturnal voids. Nocturnal void data were recorded in participant diaries. This was the second co-primary outcome.
Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4
时间窗: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
The number of nocturnal voids was the average over 3 consecutive 24-hours periods prior to Day 1 and prior to the week 4 visit as recorded in participant diaries. This was the first co-primary outcome.
次要结局
- Part I: Change From Baseline in Total Reported Sleep Time at Week 4(- Week 3 to Day 1 (Baseline), Week 4 (end of Part I))
- Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169(- Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169)
- Part II: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169(- Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169)
- Part I: Change From Baseline in Initial Period of Undisturbed Sleep at Week 4(- Week 3 to Day 1 (Baseline), Week 4 (end of Part I))
- Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4(- Week 3 to Day 1 (Baseline), Week 4 (end of Part I))
- Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4(- Week 3 to Day 1 (Baseline), Week 4 (end of Part I))
- Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II(Week 5 up to Day 169)
- Part I: Change From Baseline in Quality of Sleep as Assessed by the Global Score of the Pittsburgh Sleep Quality Index (PSQI) at Week 4(- Week 3 to Day 1 (Baseline), Week 4 (end of Part I))
- Part I: Change From Baseline in the Mental Health Summary and the Physical Health Summary of the Short Form-12 Version 2 (SF-12v2) at Week 4(- Week 3 to Day 1 (Baseline), Week 4 (end of Part I))
- Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I(Day 1 up to Week 4 (end of Part I))