Nocturia
Conditions
Keywords
nocturia, bladder function
Brief summary
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.
Interventions
DRUGDesmopressin
Desmopressin oral lyophilisate melt tablet, in either the 10, 25, 50, or 100 μg dosage, for sublingual administration
DRUGPlacebo
Placebo melt tablet for sublingual administration
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Action Defined as the Time With Urine Osmolality Above 200 mOsm/kg - Period 1 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time When Urine Production <0.12 ml/kg/Min | 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 due to water-loading 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 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 | Duration of first period of undisturbed sleep is defined as the length of time from initial sleep to first awakening. Records of nocturia and sleep over three consecutive days per week were kept in voiding-sleep diaries by study participants. The average length of first period of undisturbed sleep of the 3 days recorded in the last week of the study (between study days 25-32) was compared to average baseline readings. |
| 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 | Total sleep time is defined as the time spent asleep from initial sleep to final awakening. Records of nocturia and sleep over three consecutive days per week were kept in voiding-sleep diaries by study participants. The average of the total time asleep of the 3 days recorded in the last week of the study (between study days 25-32) was compared to average baseline readings. |
| 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 | Number of daytime voids was recorded over three consecutive days per week in diaries kept by study participants. The average number of daytime voids of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings. |
| 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 | Number of voids in 24 hours was recorded over three consecutive days per week in diaries kept by study participants. The average number of 24-hour voids of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings. |
| 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 | Nocturnal urine volume was recorded over three consecutive days per week in diaries kept by study participants. The average nocturnal urine volume of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings. |
| Area Under the Urine Osmolality Curve (AUCosm) | Day 1 | Area under the urine osmolality curve, from dose administration to end of action (AUCosm). |
| 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 | Twenty-four hour urine volume was recorded over three consecutive days per week in diaries kept by study participants. Urine volume per body weight was calculated. The average 24-hour urine volume per kg of body weight of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings. |
| 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 | Nocturnal polyuria index is defined as a proportion of nocturnal urine volume to the 24-hour urine volume. Urine volume and time of day of those voids was recorded over three consecutive days per week in diaries kept by study participants. The average nocturnal polyuria index of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings. |
| 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 | N-QoL assesses the impact of nocturia on quality of life (QoL) and treatment outcomes. N-QoL is a self-administered questionnaire with 13 items using scales of 0 = no negative impact to QoL to the upper number = signficant negative impact to QoL. The sleep/energy domain consists of 7 questions with a scale of 0 to 28. The bother/concern domain consists of 5 questions for a scale of 0 to 20. The 13th question is an overall assessment scored from 0 to 10. The Total Score includes all 13 questions with a scale of 0 (no negative impact to QoL) to 58 (significant negative impact to QoL). |
| 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 | The Global Score of the Pittsburgh Sleep Quality Index (PSQI) is comprised of Questions 2-9 with a total scale of 0 (no difficulty sleeping) to 21 (severe difficulty). The change in Global Score is Global Score at the end of period 2 (day 32) - Global Score at the start of Period 2 (day 4). A negative change indicates an improvement in quality of life. |
| Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | Days 4- 32 | Serum sodium levels were monitored throughout the trial as part of the clinical chemistry panel. If the value was ≤125 mEq/L, the participant was to be withdrawn from the trial and treatment stopped immediately. This outcome reports participants' lowest recorded serum sodium levels during the second treatment period. |
| 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 | Twenty-four hour urine volume was recorded over three consecutive days per week in diaries kept by study participants. The average 24-hour urine volume of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings. |
| Area Under the Urine Production Curve (AUCurine Prod) | Day 1 | Area under the urine production curve, from dose administration to end of action (AUCurine prod) |
Countries
Japan
Participant flow
Pre-assignment details
139 patients randomized and 116 treated. Withdrawals during the screening period were due to urine production did not meet \>0.12 mL/kg/min within 2 hours of dosing (22 patients) and violation of inclusion/exclusion criteria (1 patient).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days. | 23 |
| Desmopressin 10µg Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days. | 23 |
| Desmopressin 25µg Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days. | 22 |
| Desmopressin 50µg Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days. | 21 |
| Desmopressin 100µg Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days. | 24 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Period 1: Single Dose | Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Period 1: Single Dose | Insufficient urine production | 0 | 1 | 0 | 0 | 0 |
| Period 1: Single Dose | Protocol Violation | 0 | 1 | 0 | 0 | 0 |
| Period 2: Daily Dose for 28 Days | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Period 2: Daily Dose for 28 Days | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Desmopressin 100µg | Desmopressin 50µg | Desmopressin 25µg | Desmopressin 10µg |
|---|---|---|---|---|---|---|
| 24-Hour Urine Volume | 1742.32 mL STANDARD_DEVIATION 344.99 | 1775.93 mL STANDARD_DEVIATION 423.67 | 1785.65 mL STANDARD_DEVIATION 404.67 | 1848.32 mL STANDARD_DEVIATION 497.96 | 1881.67 mL STANDARD_DEVIATION 399.42 | 1632.17 mL STANDARD_DEVIATION 454.75 |
| Age Continuous | 64.3 years STANDARD_DEVIATION 6.4 | 65.4 years STANDARD_DEVIATION 6.1 | 65.3 years STANDARD_DEVIATION 5.6 | 64.9 years STANDARD_DEVIATION 7.1 | 65.5 years STANDARD_DEVIATION 6 | 67.0 years STANDARD_DEVIATION 5.6 |
| Age, Customized >=55 and <65 years | 12 participants | 52 participants | 12 participants | 10 participants | 10 participants | 8 participants |
| Age, Customized >=65 and <76 years | 11 participants | 61 participants | 12 participants | 11 participants | 12 participants | 15 participants |
| Nocturnal Urine Volume | 634.78 mL STANDARD_DEVIATION 210.54 | 616.64 mL STANDARD_DEVIATION 200.13 | 631.78 mL STANDARD_DEVIATION 175.02 | 635.87 mL STANDARD_DEVIATION 211.53 | 613.06 mL STANDARD_DEVIATION 182.47 | 568.55 mL STANDARD_DEVIATION 227.4 |
| Number of 24-hour Voids | 9.83 voids STANDARD_DEVIATION 1.52 | 10.58 voids STANDARD_DEVIATION 1.83 | 10.60 voids STANDARD_DEVIATION 1.6 | 10.95 voids STANDARD_DEVIATION 2.12 | 11.15 voids STANDARD_DEVIATION 1.79 | 10.41 voids STANDARD_DEVIATION 1.94 |
| Number of Daytime Voids | 7.67 daytime voids STANDARD_DEVIATION 1.48 | 8.26 daytime voids STANDARD_DEVIATION 1.74 | 8.33 daytime voids STANDARD_DEVIATION 1.65 | 8.67 daytime voids STANDARD_DEVIATION 1.99 | 8.70 daytime voids STANDARD_DEVIATION 1.53 | 7.97 daytime voids STANDARD_DEVIATION 1.91 |
| Number of Nocturnal Voids | 2.16 nocturnal voids STANDARD_DEVIATION 0.26 | 2.32 nocturnal voids STANDARD_DEVIATION 0.42 | 2.26 nocturnal voids STANDARD_DEVIATION 0.38 | 2.29 nocturnal voids STANDARD_DEVIATION 0.44 | 2.45 nocturnal voids STANDARD_DEVIATION 0.45 | 2.43 nocturnal voids STANDARD_DEVIATION 0.51 |
| Sex: Female, Male Female | 12 Participants | 58 Participants | 12 Participants | 11 Participants | 11 Participants | 12 Participants |
| Sex: Female, Male Male | 11 Participants | 55 Participants | 12 Participants | 10 Participants | 11 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 23 | 1 / 25 | 1 / 22 | 4 / 22 | 7 / 24 | 3 / 23 | 1 / 23 | 4 / 22 | 1 / 22 | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 25 | 0 / 22 | 0 / 22 | 0 / 24 | 0 / 23 | 0 / 23 | 0 / 22 | 0 / 22 | 0 / 23 |
Outcome results
Primary
Change From Baseline in Number of Nocturnal Voids After 28 Days of Treatment - Period 2
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.
Time frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Number of Nocturnal Voids After 28 Days of Treatment - Period 2 | -0.735 nocturnal voids |
| Desmopressin 10µg | Change From Baseline in Number of Nocturnal Voids After 28 Days of Treatment - Period 2 | -1.007 nocturnal voids |
| Desmopressin 25µg | Change From Baseline in Number of Nocturnal Voids After 28 Days of Treatment - Period 2 | -1.282 nocturnal voids |
| Desmopressin 50µg | Change From Baseline in Number of Nocturnal Voids After 28 Days of Treatment - Period 2 | -1.589 nocturnal voids |
| Desmopressin 100µg | Change From Baseline in Number of Nocturnal Voids After 28 Days of Treatment - Period 2 | -1.624 nocturnal voids |
p-value: 0.19495% CI: [-0.685, -0.141]ANCOVA
p-value: 0.01595% CI: [-0.985, -0.108]ANCOVA
p-value: <0.00195% CI: [-1.317, -0.391]ANCOVA
p-value: 0.00195% CI: [-1.426, -0.351]ANCOVA
Primary
Duration of Action Defined as the Time With Urine Osmolality Above 200 mOsm/kg - Period 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.
Time frame: Day 1
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Duration of Action Defined as the Time With Urine Osmolality Above 200 mOsm/kg - Period 1 | 0.00 hours | Standard Deviation 0 |
| Desmopressin 10µg | Duration of Action Defined as the Time With Urine Osmolality Above 200 mOsm/kg - Period 1 | 0.09 hours | Standard Deviation 0.32 |
| Desmopressin 25µg | Duration of Action Defined as the Time With Urine Osmolality Above 200 mOsm/kg - Period 1 | 2.00 hours | Standard Deviation 3.56 |
| Desmopressin 50µg | Duration of Action Defined as the Time With Urine Osmolality Above 200 mOsm/kg - Period 1 | 3.45 hours | Standard Deviation 2.88 |
| Desmopressin 100µg | Duration of Action Defined as the Time With Urine Osmolality Above 200 mOsm/kg - Period 1 | 5.74 hours | Standard Deviation 2.99 |
p-value: 0.211t-test, 2 sided
p-value: 0.01t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
Secondary
Area Under the Urine Osmolality Curve (AUCosm)
Area under the urine osmolality curve, from dose administration to end of action (AUCosm).
Time frame: Day 1
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Urine Osmolality Curve (AUCosm) | 0.00 h*mOsm/kg | Standard Deviation 0 |
| Desmopressin 10µg | Area Under the Urine Osmolality Curve (AUCosm) | 24.67 h*mOsm/kg | Standard Deviation 97.5 |
| Desmopressin 25µg | Area Under the Urine Osmolality Curve (AUCosm) | 852.00 h*mOsm/kg | Standard Deviation 1576.1 |
| Desmopressin 50µg | Area Under the Urine Osmolality Curve (AUCosm) | 1551.01 h*mOsm/kg | Standard Deviation 1501.21 |
| Desmopressin 100µg | Area Under the Urine Osmolality Curve (AUCosm) | 3112.53 h*mOsm/kg | Standard Deviation 2131.69 |
Secondary
Area Under the Urine Production Curve (AUCurine Prod)
Area under the urine production curve, from dose administration to end of action (AUCurine prod)
Time frame: Day 1
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Urine Production Curve (AUCurine Prod) | 59.34 h*mL | Standard Deviation 153.78 |
| Desmopressin 10µg | Area Under the Urine Production Curve (AUCurine Prod) | 214.24 h*mL | Standard Deviation 266.86 |
| Desmopressin 25µg | Area Under the Urine Production Curve (AUCurine Prod) | 297.17 h*mL | Standard Deviation 322.51 |
| Desmopressin 50µg | Area Under the Urine Production Curve (AUCurine Prod) | 522.99 h*mL | Standard Deviation 283.9 |
| Desmopressin 100µg | Area Under the Urine Production Curve (AUCurine Prod) | 537.08 h*mL | Standard Deviation 330.67 |
Secondary
Change From Baseline in 24-Hour Urine Production Per Body Weight at Approximately Day 32
Twenty-four hour urine volume was recorded over three consecutive days per week in diaries kept by study participants. Urine volume per body weight was calculated. The average 24-hour urine volume per kg of body weight of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.
Time frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in 24-Hour Urine Production Per Body Weight at Approximately Day 32 | -2.017 ml/kg | Standard Deviation 6.205 |
| Desmopressin 10µg | Change From Baseline in 24-Hour Urine Production Per Body Weight at Approximately Day 32 | -0.096 ml/kg | Standard Deviation 6.814 |
| Desmopressin 25µg | Change From Baseline in 24-Hour Urine Production Per Body Weight at Approximately Day 32 | -3.523 ml/kg | Standard Deviation 7.621 |
| Desmopressin 50µg | Change From Baseline in 24-Hour Urine Production Per Body Weight at Approximately Day 32 | -4.573 ml/kg | Standard Deviation 6.183 |
| Desmopressin 100µg | Change From Baseline in 24-Hour Urine Production Per Body Weight at Approximately Day 32 | -3.058 ml/kg | Standard Deviation 6.263 |
Secondary
Change From Baseline in 24-Hour Urine Volume at Approximately Day 32
Twenty-four hour urine volume was recorded over three consecutive days per week in diaries kept by study participants. The average 24-hour urine volume of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.
Time frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in 24-Hour Urine Volume at Approximately Day 32 | -104.47 ml | Standard Deviation 386.27 |
| Desmopressin 10µg | Change From Baseline in 24-Hour Urine Volume at Approximately Day 32 | -19.47 ml | Standard Deviation 371.72 |
| Desmopressin 25µg | Change From Baseline in 24-Hour Urine Volume at Approximately Day 32 | -201.83 ml | Standard Deviation 487.49 |
| Desmopressin 50µg | Change From Baseline in 24-Hour Urine Volume at Approximately Day 32 | -270.53 ml | Standard Deviation 344.29 |
| Desmopressin 100µg | Change From Baseline in 24-Hour Urine Volume at Approximately Day 32 | -187.25 ml | Standard Deviation 369.61 |
Secondary
Change From Baseline in Duration of First Period of Undisturbed Sleep After 28 Days of Treatment - Period 2
Duration of first period of undisturbed sleep is defined as the length of time from initial sleep to first awakening. Records of nocturia and sleep over three consecutive days per week were kept in voiding-sleep diaries by study participants. The average length of first period of undisturbed sleep of the 3 days recorded in the last week of the study (between study days 25-32) was compared to average baseline readings.
Time frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Duration of First Period of Undisturbed Sleep After 28 Days of Treatment - Period 2 | 68.39 minutes | Standard Deviation 93.32 |
| Desmopressin 10µg | Change From Baseline in Duration of First Period of Undisturbed Sleep After 28 Days of Treatment - Period 2 | 101.85 minutes | Standard Deviation 120.26 |
| Desmopressin 25µg | Change From Baseline in Duration of First Period of Undisturbed Sleep After 28 Days of Treatment - Period 2 | 113.45 minutes | Standard Deviation 120.22 |
| Desmopressin 50µg | Change From Baseline in Duration of First Period of Undisturbed Sleep After 28 Days of Treatment - Period 2 | 190.77 minutes | Standard Deviation 124.32 |
| Desmopressin 100µg | Change From Baseline in Duration of First Period of Undisturbed Sleep After 28 Days of Treatment - Period 2 | 194.25 minutes | Standard Deviation 99.17 |
Secondary
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
N-QoL assesses the impact of nocturia on quality of life (QoL) and treatment outcomes. N-QoL is a self-administered questionnaire with 13 items using scales of 0 = no negative impact to QoL to the upper number = signficant negative impact to QoL. The sleep/energy domain consists of 7 questions with a scale of 0 to 28. The bother/concern domain consists of 5 questions for a scale of 0 to 20. The 13th question is an overall assessment scored from 0 to 10. The Total Score includes all 13 questions with a scale of 0 (no negative impact to QoL) to 58 (significant negative impact to QoL).
Time frame: Approximately Day 4 (start of period 2) and Day 32
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | Sleep/Energy subscale | 7.77 units on a scale | Standard Deviation 11.66 |
| Placebo | 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 | Total Score | 7.04 units on a scale | Standard Deviation 14.05 |
| Placebo | 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 | Bother/Concern subscale | 6.36 units on a scale | Standard Deviation 19.02 |
| Desmopressin 10µg | 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 | Bother/Concern subscale | 8.99 units on a scale | Standard Deviation 16.91 |
| Desmopressin 10µg | 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 | Sleep/Energy subscale | 10.69 units on a scale | Standard Deviation 15.33 |
| Desmopressin 10µg | 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 | Total Score | 9.98 units on a scale | Standard Deviation 14.65 |
| Desmopressin 25µg | 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 | Bother/Concern subscale | 16.33 units on a scale | Standard Deviation 18.35 |
| Desmopressin 25µg | 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 | Sleep/Energy subscale | 13.26 units on a scale | Standard Deviation 15.46 |
| Desmopressin 25µg | 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 | Total Score | 14.78 units on a scale | Standard Deviation 16.28 |
| Desmopressin 50µg | 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 | Sleep/Energy subscale | 12.30 units on a scale | Standard Deviation 10.82 |
| Desmopressin 50µg | 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 | Total Score | 11.44 units on a scale | Standard Deviation 13 |
| Desmopressin 50µg | 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 | Bother/Concern subscale | 10.67 units on a scale | Standard Deviation 19.37 |
| Desmopressin 100µg | 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 | Bother/Concern subscale | 10.15 units on a scale | Standard Deviation 14 |
| Desmopressin 100µg | 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 | Sleep/Energy subscale | 8.52 units on a scale | Standard Deviation 12.23 |
| Desmopressin 100µg | 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 | Total Score | 9.39 units on a scale | Standard Deviation 11.11 |
Secondary
Change From Baseline in Nocturnal Polyuria Index at Approximately Day 32
Nocturnal polyuria index is defined as a proportion of nocturnal urine volume to the 24-hour urine volume. Urine volume and time of day of those voids was recorded over three consecutive days per week in diaries kept by study participants. The average nocturnal polyuria index of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.
Time frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Nocturnal Polyuria Index at Approximately Day 32 | -4.72 nocturnal urine volume / 24-hour urine | Standard Deviation 6.75 |
| Desmopressin 10µg | Change From Baseline in Nocturnal Polyuria Index at Approximately Day 32 | -7.82 nocturnal urine volume / 24-hour urine | Standard Deviation 6.65 |
| Desmopressin 25µg | Change From Baseline in Nocturnal Polyuria Index at Approximately Day 32 | -8.61 nocturnal urine volume / 24-hour urine | Standard Deviation 9.28 |
| Desmopressin 50µg | Change From Baseline in Nocturnal Polyuria Index at Approximately Day 32 | -13.56 nocturnal urine volume / 24-hour urine | Standard Deviation 9.72 |
| Desmopressin 100µg | Change From Baseline in Nocturnal Polyuria Index at Approximately Day 32 | -16.00 nocturnal urine volume / 24-hour urine | Standard Deviation 6.87 |
Secondary
Change From Baseline in Nocturnal Urine Volume at Approximately Day 32
Nocturnal urine volume was recorded over three consecutive days per week in diaries kept by study participants. The average nocturnal urine volume of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.
Time frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Nocturnal Urine Volume at Approximately Day 32 | -114.70 ml | Standard Deviation 224.53 |
| Desmopressin 10µg | Change From Baseline in Nocturnal Urine Volume at Approximately Day 32 | -140.68 ml | Standard Deviation 168.62 |
| Desmopressin 25µg | Change From Baseline in Nocturnal Urine Volume at Approximately Day 32 | -209.87 ml | Standard Deviation 262.89 |
| Desmopressin 50µg | Change From Baseline in Nocturnal Urine Volume at Approximately Day 32 | -295.02 ml | Standard Deviation 196.71 |
| Desmopressin 100µg | Change From Baseline in Nocturnal Urine Volume at Approximately Day 32 | -333.22 ml | Standard Deviation 154.05 |
Secondary
Change From Baseline in Number of 24-hour Urine Voids at Approximately Day 32
Number of voids in 24 hours was recorded over three consecutive days per week in diaries kept by study participants. The average number of 24-hour voids of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.
Time frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Number of 24-hour Urine Voids at Approximately Day 32 | -0.15 voids | Standard Deviation 1.71 |
| Desmopressin 10µg | Change From Baseline in Number of 24-hour Urine Voids at Approximately Day 32 | -0.47 voids | Standard Deviation 1.93 |
| Desmopressin 25µg | Change From Baseline in Number of 24-hour Urine Voids at Approximately Day 32 | -1.19 voids | Standard Deviation 1.85 |
| Desmopressin 50µg | Change From Baseline in Number of 24-hour Urine Voids at Approximately Day 32 | -1.33 voids | Standard Deviation 1.81 |
| Desmopressin 100µg | Change From Baseline in Number of 24-hour Urine Voids at Approximately Day 32 | -0.96 voids | Standard Deviation 1.69 |
Secondary
Change From Baseline in Number of Daytime Voids at Approximately Day 32
Number of daytime voids was recorded over three consecutive days per week in diaries kept by study participants. The average number of daytime voids of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.
Time frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Number of Daytime Voids at Approximately Day 32 | 0.49 voids | Standard Deviation 1.33 |
| Desmopressin 10µg | Change From Baseline in Number of Daytime Voids at Approximately Day 32 | 0.68 voids | Standard Deviation 1.53 |
| Desmopressin 25µg | Change From Baseline in Number of Daytime Voids at Approximately Day 32 | 0.15 voids | Standard Deviation 1.66 |
| Desmopressin 50µg | Change From Baseline in Number of Daytime Voids at Approximately Day 32 | 0.23 voids | Standard Deviation 1.51 |
| Desmopressin 100µg | Change From Baseline in Number of Daytime Voids at Approximately Day 32 | 0.63 voids | Standard Deviation 1.74 |
Secondary
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
The Global Score of the Pittsburgh Sleep Quality Index (PSQI) is comprised of Questions 2-9 with a total scale of 0 (no difficulty sleeping) to 21 (severe difficulty). The change in Global Score is Global Score at the end of period 2 (day 32) - Global Score at the start of Period 2 (day 4). A negative change indicates an improvement in quality of life.
Time frame: Approximately Day 4 (start of period 2) and Day 32
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 | -1.2 units on a scale | Standard Deviation 2 |
| Desmopressin 10µg | 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 | -0.6 units on a scale | Standard Deviation 2.3 |
| Desmopressin 25µg | 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 | -1.5 units on a scale | Standard Deviation 2.2 |
| Desmopressin 50µg | 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 | -1.4 units on a scale | Standard Deviation 2.5 |
| Desmopressin 100µg | 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 | -1.3 units on a scale | Standard Deviation 1.8 |
Secondary
Change From Baseline in Total Sleep Time at Approximately Day 32
Total sleep time is defined as the time spent asleep from initial sleep to final awakening. Records of nocturia and sleep over three consecutive days per week were kept in voiding-sleep diaries by study participants. The average of the total time asleep of the 3 days recorded in the last week of the study (between study days 25-32) was compared to average baseline readings.
Time frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance. Missing values post baseline were imputed using last observation carried forward (LOCF) where at least one post baseline measurement was available at a visit before the missing observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total Sleep Time at Approximately Day 32 | 2.47 minutes | Standard Deviation 49.94 |
| Desmopressin 10µg | Change From Baseline in Total Sleep Time at Approximately Day 32 | -11.86 minutes | Standard Deviation 48.57 |
| Desmopressin 25µg | Change From Baseline in Total Sleep Time at Approximately Day 32 | -33.04 minutes | Standard Deviation 116.09 |
| Desmopressin 50µg | Change From Baseline in Total Sleep Time at Approximately Day 32 | 6.81 minutes | Standard Deviation 69.04 |
| Desmopressin 100µg | Change From Baseline in Total Sleep Time at Approximately Day 32 | 14.07 minutes | Standard Deviation 54.06 |
Secondary
Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32)
Serum sodium levels were monitored throughout the trial as part of the clinical chemistry panel. If the value was ≤125 mEq/L, the participant was to be withdrawn from the trial and treatment stopped immediately. This outcome reports participants' lowest recorded serum sodium levels during the second treatment period.
Time frame: Days 4- 32
Population: Safety population which included all randomised and exposed participants. Participants were analysed according to the actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | >= 135 mEq/L | 23 participants |
| Placebo | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | <130 mEq/L | 0 participants |
| Placebo | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | >=130 mEq/L to <135 mEq/L | 0 participants |
| Desmopressin 10µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | >=130 mEq/L to <135 mEq/L | 0 participants |
| Desmopressin 10µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | >= 135 mEq/L | 23 participants |
| Desmopressin 10µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | <130 mEq/L | 0 participants |
| Desmopressin 25µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | >=130 mEq/L to <135 mEq/L | 1 participants |
| Desmopressin 25µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | >= 135 mEq/L | 21 participants |
| Desmopressin 25µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | <130 mEq/L | 0 participants |
| Desmopressin 50µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | >= 135 mEq/L | 21 participants |
| Desmopressin 50µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | <130 mEq/L | 0 participants |
| Desmopressin 50µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | >=130 mEq/L to <135 mEq/L | 1 participants |
| Desmopressin 100µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | >=130 mEq/L to <135 mEq/L | 0 participants |
| Desmopressin 100µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | >= 135 mEq/L | 23 participants |
| Desmopressin 100µg | Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) | <130 mEq/L | 0 participants |
Secondary
Time When Urine Production <0.12 ml/kg/Min
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 due to water-loading 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.
Time frame: Day 1
Population: Per protocol population, consisting of treated participants without major protocol violations and with \>=80% treatment compliance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time When Urine Production <0.12 ml/kg/Min | 0.41 hours | Standard Deviation 1.15 |
| Desmopressin 10µg | Time When Urine Production <0.12 ml/kg/Min | 1.67 hours | Standard Deviation 2.16 |
| Desmopressin 25µg | Time When Urine Production <0.12 ml/kg/Min | 3.50 hours | Standard Deviation 4.17 |
| Desmopressin 50µg | Time When Urine Production <0.12 ml/kg/Min | 6.05 hours | Standard Deviation 3.56 |
| Desmopressin 100µg | Time When Urine Production <0.12 ml/kg/Min | 8.20 hours | Standard Deviation 2.59 |