A Multi-centre, Double-blind, Randomised, Placebo-controlled, Parallel-group, Comparative Trial to Investigate the Dose-Response of 4 Different Dose Levels of Minirin Melt and Placebo in Water-loaded Male and Female Japanese Nocturia Patients (Single Dose), and to Study the Efficacy of 4 Different Dose Levels of Minirin Melt and Placebo After 28 Days of Dosing (Multiple Doses)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 116
- 试验地点
- 36
- 主要终点
- Duration of Action Defined as the Time With Urine Osmolality Above 200 mOsm/kg - Period 1
研究概览
简要总结
This is a multi-centre, randomised, placebo-controlled, double-blind, parallel-group comparative trial to be conducted in nocturia patients. The trial is designed to characterize the dose-response relationship of Minirin (desmopressin) Melt in order to establish correct dose recommendations in the target patient population. In particular, the trial is designed to link the duration of action to the clinical endpoint. Furthermore, the trial is designed to describe the safety of four different dose levels of desmopressin.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Given written informed consent prior to any trial-related activity is performed
- •Aged 55-75 years
- •Mean number of nocturnal voids of at least two per night
- •Reached post-menopause (applicable to females only)
排除标准
- •Evidence of bladder outlet obstruction (BOO); or a urine flow of less than 5 mL/s (applicable to males only)
- •A surgical treatment for BOO or prostatic hyperplasia within the past 6 months (applicable to males only)
- •Showing symptoms of any of the following diseases and having a mean number of nocturnal voids exceeding four per night: Benign prostatic hyperplasia, overactive bladder, interstitial cystitis, severe stress urinary incontinence
- •Psychosomatic or habitual polydipsia
- •Urinary retention; or a post void residual volume in excess of 150 mL
- •A history or complication of urologic malignancy (e.g. bladder cancer or prostate cancer)
- •Complication of genito-urinary pathology (e.g. infection, stone, or neoplasia)
- •Complication of neurogenic detrusor activity
- •Complication or suspicion of heart failure
- •Uncontrolled hypertension
- •Uncontrolled diabetes mellitus
- •Complication of hepatobiliary disease
- •Abnormal serum creatinine level
- •Complication of hyponatraemia, or serum sodium level <135 mEq/L
- •Central or nephrogenic diabetes insipidus (CDI or NDI)
- •Syndrome of inappropriate antidiuretic hormone (SIADH)
- •Obstructive sleep apnea
- •Alcohol dependency or drug abuse
- •A job or lifestyle that may interfere with regular night-time sleep
- •Previous desmopressin treatment
- •Treatment with another investigational product within the past 3 months
- •A need for treatment with a prohibited concomitant drug for a complication or other problem
- •A mental condition, the lack of decision-making ability, dementia or a speech handicap
- •Any other reason that the Investigator believes inappropriate
研究组 & 干预措施
Desmopressin 10µg
Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.
干预措施: Desmopressin (Drug)
Desmopressin 25µg
Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.
干预措施: Desmopressin (Drug)
Desmopressin 50µg
Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.
干预措施: Desmopressin (Drug)
Desmopressin 100µg
Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
干预措施: Desmopressin (Drug)
Placebo
Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Duration of Action Defined as the Time With Urine Osmolality Above 200 mOsm/kg - Period 1
时间窗: Day 1
Participants were water-loaded to suppress the endogenous release of vasopressin, thus all antidiuretic activity was generated by desmopressin only. Water-loading was initiated 2 hours before dosing on Day 1. Urine volume was registered and samples for osmolality check were collected every 30 minutes as long as there was an antidiuretic action defined as a urine production \<0.12 mL/kg/min. The hydration should have lasted until end of action, defined as when the urine production returned to \>0.12 mL/kg/min, but no longer than 12 hours.
Change From Baseline in Number of Nocturnal Voids After 28 Days of Treatment - Period 2
时间窗: 3 days between study days -6 to 0 (Baseline), and days 25 to 32
Records of nocturia and sleep over three consecutive days per week were kept in voiding-sleep diaries by study participants. The average number of nocturnal voids of the 3 days recorded in the last week of the study (between study days 25-32) was compared to average baseline readings.
次要结局
- Change From Baseline in Nocturnal Urine Volume at Approximately Day 32(3 days between study days -6 to 0 (Baseline), and days 25 to 32)
- Area Under the Urine Osmolality Curve (AUCosm)(Day 1)
- Area Under the Urine Production Curve (AUCurine Prod)(Day 1)
- Time When Urine Production <0.12 ml/kg/Min(Day 1)
- Change From Baseline in Duration of First Period of Undisturbed Sleep After 28 Days of Treatment - Period 2(3 days between study days -6 to 0 (Baseline), and days 25 to 32)
- Change From Baseline in Total Sleep Time at Approximately Day 32(3 days between study days -6 to 0 (Baseline), and days 25 to 32)
- Change From Baseline in Number of Daytime Voids at Approximately Day 32(3 days between study days -6 to 0 (Baseline), and days 25 to 32)
- Change From Baseline in Number of 24-hour Urine Voids at Approximately Day 32(3 days between study days -6 to 0 (Baseline), and days 25 to 32)
- Change From Baseline in 24-Hour Urine Volume at Approximately Day 32(3 days between study days -6 to 0 (Baseline), and days 25 to 32)
- Change From Baseline in 24-Hour Urine Production Per Body Weight at Approximately Day 32(3 days between study days -6 to 0 (Baseline), and days 25 to 32)
- Change From Baseline in Nocturnal Polyuria Index at Approximately Day 32(3 days between study days -6 to 0 (Baseline), and days 25 to 32)
- Change From Baseline in Nocturia-Related Quality of Life Based on Evaluation Provided by Nocturia Quality of Life Questionnaire (N-QoL) at Approximately Day 32(Approximately Day 4 (start of period 2) and Day 32)
- Change From Baseline in Sleep Related Quality of Life Based on the Global Score of the Pittsburgh Sleep Quality Index (PSQI) at Approximately Day 32(Approximately Day 4 (start of period 2) and Day 32)
- Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32)(Days 4- 32)