Nocturia
Conditions
Brief summary
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.
Interventions
Oral lyophilisate of desmopressin acetate placed under the participant's tongue, without water, once daily approximately 1 hour before bedtime in the assigned dosage: 10, 25, 50 or 100 μg
DRUGPlacebo
Oral placebo placed under the participant's tongue, without water, once daily approximately 1 hour before bedtime.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent prior to the performance of any study-related activity. 2. Patients 18 years and older with an average of ≥ 2 nocturnal voids per night as determined by a 3 day frequency-volume chart during the screening period.
Exclusion criteria
Males: 1. 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 2. Surgical treatment for bladder outlet obstruction/benign prostatic hyperplasia performed within the past 6 months Females: 3. Pregnancy. Females of reproductive age must have documentation of a reliable method of contraception. 4. Use of pessary for pelvic prolapse. 5. Unexplained pelvic mass. Males and Females: 6. 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. 7. Current or past urologic malignancy (e.g., bladder cancer, prostate cancer). 8. Clinical evidence of current genitourinary tract pathology that could interfere with voiding. 9. History of neurogenic detrusor activity (previously known as detrusor hyperreflexia). 10. Suspicion or evidence of cardiac failure. 11. Uncontrolled hypertension. 12. Uncontrolled diabetes mellitus. 13. Renal insufficiency. Serum creatinine must be within normal limits and estimated glomerular filtration rate (eGFR) \>=60 mL/min. 14. 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. 15. Hyponatremia. Serum sodium level must be within normal limits 16. Syndrome of Inappropriate antidiuretic hormone secretion (SIADH). 17. Diabetes insipidus (urine output \> 40 ml/kg over 24 hours) as determined by the 3-day voiding diary. 18. Psychogenic or habitual polydipsia 19. Obstructive sleep apnea Other 20. Known alcohol or substance abuse 21. Work or lifestyle potentially interfering with regular nighttime sleep (e.g., shift workers) 22. Previous desmopressin treatment for nocturia. 23. 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. 24. 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. 25. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | - 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. |
| Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4 | - 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Total sleep time was recorded by participants in study diaries. |
| 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) | Initial period of undisturbed sleep was the time elapsed from first falling asleep until either first void or morning arising. Data were captured in patient diaries. |
| 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) | The ICIQ-N is a self-administered questionnaire designed to assess the frequency and bother of daytime and nighttime urination. Subjects were asked to rate the degree of bother of daytime urination and nighttime urination on a scale ranging from 0 (not at all) to 10 (a great deal). Higher numbers indicate lower quality of life. |
| 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) | The NQoL questionnaire is a self-administered questionnaire designed to assess the impact of nocturia on quality of life. It contains a sleep/energy domain (6 questions), a bother/concern domain (6 questions), and 1 global QoL question. The twelve core questions are scored on a 0 to 4 scale with higher numbers indicating a better quality of life. Domain summary scores were calculated by transforming the raw score into a 0-100 scale with higher numbers indicating a better quality of life. |
| 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 outcomes tested the durability of the effect observed in Part I. The number of nocturnal voids was the average over 3 consecutive 24-hours periods prior to Part I baseline and prior to the Part II visit as recorded in participant diaries. |
| 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) | The SF-12v2 was used to measure the impact of nocturia and lack of sleep on general quality of life. The SF-12 consists of 12 questions. Data were analyzed using norm-based scoring and summarized along 2 dimensions: Physical Health Summary and Mental Health Summary. Each summary has a range from 0 (poor health) to 100 (highest level of health). Higher numbers indicate better quality of life. |
| Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Day 1 up to Week 4 (end of Part I) | A treatment-emergent adverse event (AE) was any AE occurring during the treatment period or a pretreatment AE that worsened in intensity during the treatment period. The treatment period was the period during which a subject received investigational medicinal product. If a subject discontinued the investigational medicinal product, the date of last dose was the last day of the treatment period. |
| Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Week 5 up to Day 169 | A treatment-emergent adverse event (AE) was any AE occurring during the treatment period or a pretreatment AE that worsened in intensity during the treatment period. The treatment period was the period during which a subject received investigational medicinal product. If a subject discontinued the investigational medicinal product, the date of last dose was the last day of the treatment period. |
| 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) | The PSQI is a self-administered 19-item questionnaire designed to assess sleep quality and disturbances. The global score ranges from 0 (better sleep quality) to 21 (worse sleep quality). Higher numbers indicate lower quality of life. |
| 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 II outcomes tested the durability of the effect observed in Part I. Percentage of participants in each treatment arm that had a greater than 33% reduction from baseline to Days 29, 57, 113 and 169 in mean number of nocturnal voids. Nocturnal void data were recorded in participant diaries. |
Countries
Canada, United States
Participant flow
Recruitment details
Eighty-eight (88) sites were initiated in the United States and Canada, and 81 of these sites screened subjects; 78 sites enrolled and randomized subjects. A total of 1412 subjects were screened for Part I of the study; 613 subjects were screening failures.
Pre-assignment details
Potential subjects were given a sleep/voiding diary and urine collection device to record the time and volume of each void for 3 consecutive 24-hour periods. Randomization was stratified by age (\<65, ≥65 years) and by the absence/presence of nocturnal polyuria, defined as a ratio of nighttime urine volume/24-hour urine volume ≥33%.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants took a placebo 'melt' for 28 days to complete Part I of the study. In Part II, placebo patients were randomized to one of the other four treatment arms to receive active desmopressin melt for between 1-6 months (until the database for part 1 was locked and treatment was unblinded). | 156 |
| Desmopressin Melt 10 μg Participants took desmopressin melt 10 μg for 28 days to complete Part I of the study. Participants continued on this dose in study Part II for between 1-6 months (until the database for Part I was locked and treatment was unblinded). | 155 |
| Desmopressin Melt 25 μg Participants took desmopressin melt 25 μg for 28 days to complete Part I of the study. Participants continued on this dose in study Part II for between 1-6 months (until the database for Part I was locked and treatment was unblinded). | 152 |
| Desmopressin Melt 50 μg Participants took desmopressin melt 50 μg for 28 days to complete Part I of the study. Participants continued on this dose in study Part II for between 1-6 months (until the database for Part I was locked and treatment was unblinded). | 148 |
| Desmopressin Melt 100 μg Participants took desmopressin melt 100 μg for 28 days to complete Part I of the study. Participants continued on this dose in study Part II for between 1-6 months (until the database for Part I was locked and treatment was unblinded). | 146 |
| Total | 757 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Part I: 4 Week Efficacy | Adverse Event | 1 | 4 | 0 | 5 | 6 | 0 | 0 | 0 | 0 |
| Part I: 4 Week Efficacy | Lost to Follow-up | 2 | 4 | 1 | 5 | 3 | 0 | 0 | 0 | 0 |
| Part I: 4 Week Efficacy | Not Reported | 1 | 2 | 3 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part I: 4 Week Efficacy | Other, not specified | 2 | 4 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Part I: 4 Week Efficacy | Protocol Violation | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part I: 4 Week Efficacy | Serum Sodium <= 125mmol/L | 1 | 0 | 0 | 5 | 4 | 0 | 0 | 0 | 0 |
| Part I: 4 Week Efficacy | Withdrawal by Subject | 6 | 5 | 6 | 4 | 9 | 0 | 0 | 0 | 0 |
| Part II: Extension Week 5 up to Day 169 | Adverse Event | 0 | 2 | 3 | 1 | 1 | 1 | 1 | 1 | 4 |
| Part II: Extension Week 5 up to Day 169 | Decreased sodium | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 |
| Part II: Extension Week 5 up to Day 169 | Excluded medication | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part II: Extension Week 5 up to Day 169 | Lost to Follow-up | 0 | 3 | 2 | 0 | 5 | 0 | 1 | 0 | 0 |
| Part II: Extension Week 5 up to Day 169 | Not reported | 0 | 3 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part II: Extension Week 5 up to Day 169 | Other, not specified | 0 | 4 | 2 | 4 | 2 | 1 | 1 | 0 | 1 |
| Part II: Extension Week 5 up to Day 169 | Withdrawal by Subject | 0 | 15 | 7 | 7 | 10 | 4 | 2 | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo | Desmopressin Melt 10 μg | Desmopressin Melt 25 μg | Desmopressin Melt 50 μg | Desmopressin Melt 100 μg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 62.1 years STANDARD_DEVIATION 13.39 | 61.7 years STANDARD_DEVIATION 14.41 | 62.4 years STANDARD_DEVIATION 13.22 | 61.6 years STANDARD_DEVIATION 11.8 | 62.1 years STANDARD_DEVIATION 12.34 | 62.0 years STANDARD_DEVIATION 13.05 |
| Ethnic Origin Hispanic | 13 participants | 10 participants | 10 participants | 13 participants | 6 participants | 52 participants |
| Ethnic Origin Not Hispanic | 143 participants | 145 participants | 142 participants | 135 participants | 140 participants | 705 participants |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 0 participants | 2 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 3 participants | 2 participants | 2 participants | 3 participants | 6 participants | 16 participants |
| Race/Ethnicity, Customized Black/African American | 16 participants | 21 participants | 28 participants | 24 participants | 27 participants | 116 participants |
| Race/Ethnicity, Customized Caucasian | 136 participants | 123 participants | 120 participants | 119 participants | 111 participants | 609 participants |
| Race/Ethnicity, Customized Native Hawaiian/other Pacific Islander | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Other | 1 participants | 6 participants | 1 participants | 2 participants | 2 participants | 12 participants |
| Sex: Female, Male Female | 66 Participants | 73 Participants | 65 Participants | 71 Participants | 66 Participants | 341 Participants |
| Sex: Female, Male Male | 90 Participants | 82 Participants | 87 Participants | 77 Participants | 80 Participants | 416 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 | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 64 / 160 | 67 / 163 | 62 / 158 | 76 / 158 | 79 / 160 | 71 / 135 | 69 / 135 | 66 / 132 | 73 / 127 | 17 / 31 | 23 / 37 | 19 / 34 | 20 / 34 |
| serious Total, serious adverse events | 1 / 160 | 2 / 163 | 1 / 158 | 2 / 158 | 0 / 160 | 3 / 135 | 1 / 135 | 0 / 132 | 2 / 127 | 0 / 31 | 0 / 37 | 2 / 34 | 2 / 34 |
Outcome results
Primary
Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4
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.
Time frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
Population: Intent to treat (ITT) population --All randomized participants who received at least one dose of study drug and provided at least one primary efficacy measure (i.e., nocturnal voids) during Part I were included in the ITT analysis dataset
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -0.86 nocturnal voids | Standard Deviation 1.054 |
| Desmopressin Melt 10 μg | Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -0.83 nocturnal voids | Standard Deviation 1.069 |
| Desmopressin Melt 25 μg | Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -1.00 nocturnal voids | Standard Deviation 1.125 |
| Desmopressin Melt 50 μg | Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -1.18 nocturnal voids | Standard Deviation 1.187 |
| Desmopressin Melt 100 μg | Part I: Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -1.43 nocturnal voids | Standard Deviation 1.219 |
p-value: 0.930395% CI: [-0.221, 0.242]ANCOVA
p-value: 0.310495% CI: [-0.353, 0.112]ANCOVA
Comparison: The trial was to be declared positive only if in the 100 μg group, a statistically significant positive effect as compared to placebo on both co-primaries was demonstrated. And only then, the next higher dose group (i.e., 50 μg) could be claimed superior to placebo, if it showed a statistically significant improvement over placebo on both co-primaries.p-value: 0.020795% CI: [-0.511, -0.042]ANCOVA
Comparison: The trial was to be declared positive only if in the 100 μg group, a statistically significant positive effect as compared to placebo on both co-primaries was demonstrated. And only then, the next higher dose group (i.e., 50 μg) could be claimed superior to placebo, if it showed a statistically significant improvement over placebo on both co-primaries.p-value: <0.000195% CI: [-0.848, -0.378]ANCOVA
Primary
Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4
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.
Time frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
Population: Intent to treat (ITT) population --All randomized participants who received at least one dose of study drug and provided at least one primary efficacy measure (i.e., nocturnal voids) during Part I were included in the ITT analysis dataset
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4 | 47 percentage of participants |
| Desmopressin Melt 10 μg | Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4 | 47 percentage of participants |
| Desmopressin Melt 25 μg | Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4 | 50 percentage of participants |
| Desmopressin Melt 50 μg | Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4 | 53 percentage of participants |
| Desmopressin Melt 100 μg | Part I: Percentage of Participants With Greater Than 33 Percent Reduction From Baseline in Mean Number of Nocturnal Voids at Week 4 | 71 percentage of participants |
p-value: 0.94295% CI: [0.647, 1.598]Regression, Logistic
p-value: 0.552795% CI: [0.729, 1.807]Regression, Logistic
Comparison: The trial was to be declared positive only if in the 100 μg group, a statistically significant positive effect as compared to placebo on both co-primaries was demonstrated. And only then, the next higher dose group (i.e., 50 μg) could be claimed superior to placebo, if it showed a statistically significant improvement over placebo on both co-primaries.p-value: 0.266295% CI: [0.821, 2.05]Regression, Logistic
Comparison: The trial was to be declared positive only if in the 100 μg group, a statistically significant positive effect as compared to placebo on both co-primaries was demonstrated. And only then, the next higher dose group (i.e., 50 μg) could be claimed superior to placebo, if it showed a statistically significant improvement over placebo on both co-primaries.p-value: <0.000195% CI: [1.795, 4.715]Regression, Logistic
Secondary
Part I: Change From Baseline in Initial Period of Undisturbed Sleep at Week 4
Initial period of undisturbed sleep was the time elapsed from first falling asleep until either first void or morning arising. Data were captured in patient diaries.
Time frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
Population: ITT population --All randomized subjects who received at least one dose of study drug and provided at least one primary efficacy measure (i.e., number of nocturnal voids) during Part I were included in the ITT analysis dataset. Participants with both baseline and Week 4/Day 28/End of Part I data are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part I: Change From Baseline in Initial Period of Undisturbed Sleep at Week 4 | 38.7 minutes | Standard Deviation 88.79 |
| Desmopressin Melt 10 μg | Part I: Change From Baseline in Initial Period of Undisturbed Sleep at Week 4 | 50.9 minutes | Standard Deviation 111.47 |
| Desmopressin Melt 25 μg | Part I: Change From Baseline in Initial Period of Undisturbed Sleep at Week 4 | 82.7 minutes | Standard Deviation 105.57 |
| Desmopressin Melt 50 μg | Part I: Change From Baseline in Initial Period of Undisturbed Sleep at Week 4 | 85.1 minutes | Standard Deviation 109.33 |
| Desmopressin Melt 100 μg | Part I: Change From Baseline in Initial Period of Undisturbed Sleep at Week 4 | 106.7 minutes | Standard Deviation 116.18 |
Secondary
Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4
The ICIQ-N is a self-administered questionnaire designed to assess the frequency and bother of daytime and nighttime urination. Subjects were asked to rate the degree of bother of daytime urination and nighttime urination on a scale ranging from 0 (not at all) to 10 (a great deal). Higher numbers indicate lower quality of life.
Time frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
Population: Intent to treat population of participants who completed the questionnaire at both baseline and end of Part 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4 | Daytime urination: How much does it bother you? | -0.7 units on a scale | Standard Deviation 2.61 |
| Placebo | Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4 | Nighttime urination: How much does it bother you? | -1.4 units on a scale | Standard Deviation 2.86 |
| Desmopressin Melt 10 μg | Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4 | Daytime urination: How much does it bother you? | -0.7 units on a scale | Standard Deviation 2.59 |
| Desmopressin Melt 10 μg | Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4 | Nighttime urination: How much does it bother you? | -1.8 units on a scale | Standard Deviation 2.96 |
| Desmopressin Melt 25 μg | Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4 | Daytime urination: How much does it bother you? | -0.9 units on a scale | Standard Deviation 2.96 |
| Desmopressin Melt 25 μg | Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4 | Nighttime urination: How much does it bother you? | -2.1 units on a scale | Standard Deviation 3.19 |
| Desmopressin Melt 50 μg | Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4 | Nighttime urination: How much does it bother you? | -2.2 units on a scale | Standard Deviation 3.33 |
| Desmopressin Melt 50 μg | Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4 | Daytime urination: How much does it bother you? | -0.7 units on a scale | Standard Deviation 2.86 |
| Desmopressin Melt 100 μg | Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4 | Daytime urination: How much does it bother you? | -1.0 units on a scale | Standard Deviation 2.9 |
| Desmopressin Melt 100 μg | Part I: Change From Baseline in Quality of Life Assessed by The International Consultation on Incontinence Modular Questionnaire - Nocturia (ICIQ-N) at Week 4 | Nighttime urination: How much does it bother you? | -2.5 units on a scale | Standard Deviation 3.32 |
Secondary
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
The PSQI is a self-administered 19-item questionnaire designed to assess sleep quality and disturbances. The global score ranges from 0 (better sleep quality) to 21 (worse sleep quality). Higher numbers indicate lower quality of life.
Time frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
Population: Intent to treat population of participants who completed the questionnaire at both baseline and end of Part 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 | -1.6 units on a scale | Standard Deviation 2.8 |
| Desmopressin Melt 10 μg | 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 | -1.6 units on a scale | Standard Deviation 2.8 |
| Desmopressin Melt 25 μg | 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 | -1.8 units on a scale | Standard Deviation 3 |
| Desmopressin Melt 50 μg | 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 | -2.0 units on a scale | Standard Deviation 3.2 |
| Desmopressin Melt 100 μg | 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 | -1.9 units on a scale | Standard Deviation 3 |
Secondary
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
The SF-12v2 was used to measure the impact of nocturia and lack of sleep on general quality of life. The SF-12 consists of 12 questions. Data were analyzed using norm-based scoring and summarized along 2 dimensions: Physical Health Summary and Mental Health Summary. Each summary has a range from 0 (poor health) to 100 (highest level of health). Higher numbers indicate better quality of life.
Time frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
Population: Intent to treat population of participants who completed the questionnaire at both baseline and end of Part 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | Mental Health Summary | 2.4 units on a scale | Standard Deviation 7.98 |
| Placebo | 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 | Physical Health Summary | 1.0 units on a scale | Standard Deviation 6.81 |
| Desmopressin Melt 10 μg | 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 | Mental Health Summary | 2.5 units on a scale | Standard Deviation 8.06 |
| Desmopressin Melt 10 μg | 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 | Physical Health Summary | 0.5 units on a scale | Standard Deviation 6.89 |
| Desmopressin Melt 25 μg | 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 | Mental Health Summary | 2.1 units on a scale | Standard Deviation 8.16 |
| Desmopressin Melt 25 μg | 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 | Physical Health Summary | 1.2 units on a scale | Standard Deviation 7.17 |
| Desmopressin Melt 50 μg | 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 | Physical Health Summary | 0.6 units on a scale | Standard Deviation 7.1 |
| Desmopressin Melt 50 μg | 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 | Mental Health Summary | 2.2 units on a scale | Standard Deviation 8.39 |
| Desmopressin Melt 100 μg | 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 | Mental Health Summary | 1.7 units on a scale | Standard Deviation 7.73 |
| Desmopressin Melt 100 μg | 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 | Physical Health Summary | 2.3 units on a scale | Standard Deviation 6.62 |
Secondary
Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4
The NQoL questionnaire is a self-administered questionnaire designed to assess the impact of nocturia on quality of life. It contains a sleep/energy domain (6 questions), a bother/concern domain (6 questions), and 1 global QoL question. The twelve core questions are scored on a 0 to 4 scale with higher numbers indicating a better quality of life. Domain summary scores were calculated by transforming the raw score into a 0-100 scale with higher numbers indicating a better quality of life.
Time frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
Population: Intent to treat population of participants who completed the questionnaire at both baseline and end of Part 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4 | Sleep/Energy Domain | 15.2 units on a scale | Standard Deviation 19.3 |
| Placebo | Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4 | Bother/Concern Domain | 12.7 units on a scale | Standard Deviation 19.73 |
| Desmopressin Melt 10 μg | Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4 | Sleep/Energy Domain | 12.3 units on a scale | Standard Deviation 23.54 |
| Desmopressin Melt 10 μg | Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4 | Bother/Concern Domain | 14.7 units on a scale | Standard Deviation 23.42 |
| Desmopressin Melt 25 μg | Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4 | Sleep/Energy Domain | 14.6 units on a scale | Standard Deviation 18.71 |
| Desmopressin Melt 25 μg | Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4 | Bother/Concern Domain | 15.7 units on a scale | Standard Deviation 21.29 |
| Desmopressin Melt 50 μg | Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4 | Bother/Concern Domain | 15.2 units on a scale | Standard Deviation 25.46 |
| Desmopressin Melt 50 μg | Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4 | Sleep/Energy Domain | 14.7 units on a scale | Standard Deviation 20.92 |
| Desmopressin Melt 100 μg | Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4 | Sleep/Energy Domain | 16.3 units on a scale | Standard Deviation 21.09 |
| Desmopressin Melt 100 μg | Part I: Change From Baseline in the Two Domain Scores of the Nocturia Quality of Life (NQoL) Questionnaire at Week 4 | Bother/Concern Domain | 18.2 units on a scale | Standard Deviation 23.29 |
Secondary
Part I: Change From Baseline in Total Reported Sleep Time at Week 4
Total sleep time was recorded by participants in study diaries.
Time frame: - Week 3 to Day 1 (Baseline), Week 4 (end of Part I)
Population: Intent to treat (ITT) population --All randomized subjects who received at least one dose of study drug and provided at least one primary efficacy measure (i.e., number of nocturnal voids) during Part I were included in the ITT analysis dataset. Participants analyzed had baseline and Week 4/Day 28/End of Part 1 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part I: Change From Baseline in Total Reported Sleep Time at Week 4 | 24.6 minutes | Standard Deviation 80.66 |
| Desmopressin Melt 10 μg | Part I: Change From Baseline in Total Reported Sleep Time at Week 4 | 7.8 minutes | Standard Deviation 58.55 |
| Desmopressin Melt 25 μg | Part I: Change From Baseline in Total Reported Sleep Time at Week 4 | 15.9 minutes | Standard Deviation 53.92 |
| Desmopressin Melt 50 μg | Part I: Change From Baseline in Total Reported Sleep Time at Week 4 | 24.9 minutes | Standard Deviation 72.21 |
| Desmopressin Melt 100 μg | Part I: Change From Baseline in Total Reported Sleep Time at Week 4 | 19.0 minutes | Standard Deviation 68.94 |
Secondary
Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169
Part II outcomes tested the durability of the effect observed in Part I. The number of nocturnal voids was the average over 3 consecutive 24-hours periods prior to Part I baseline and prior to the Part II visit as recorded in participant diaries.
Time frame: - Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169
Population: Observed Cases (OC) Analysis Set which consisted of participants who had information on mean number of nocturnal voids for both the screening visit and the final visit in Part I (Day 28) and did not have any major protocol deviations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 29 (n=104,100,93,104,22,28,27,22) | -1.12 nocturnal voids | Standard Deviation 1.161 |
| Placebo | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 57 (n=86,85,78,81,17,24,21,16) | -1.14 nocturnal voids | Standard Deviation 1.147 |
| Placebo | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 113 (n=53,56,49,47,11,15,13,11) | -1.31 nocturnal voids | Standard Deviation 1.195 |
| Placebo | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 169 (n=17,15,17,15,3,3,4,2) | -1.47 nocturnal voids | Standard Deviation 1.537 |
| Desmopressin Melt 10 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 169 (n=17,15,17,15,3,3,4,2) | -1.71 nocturnal voids | Standard Deviation 1.214 |
| Desmopressin Melt 10 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 57 (n=86,85,78,81,17,24,21,16) | -1.42 nocturnal voids | Standard Deviation 1.231 |
| Desmopressin Melt 10 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 29 (n=104,100,93,104,22,28,27,22) | -1.31 nocturnal voids | Standard Deviation 1.163 |
| Desmopressin Melt 10 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 113 (n=53,56,49,47,11,15,13,11) | -1.56 nocturnal voids | Standard Deviation 1.158 |
| Desmopressin Melt 25 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 29 (n=104,100,93,104,22,28,27,22) | -1.43 nocturnal voids | Standard Deviation 1.273 |
| Desmopressin Melt 25 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 169 (n=17,15,17,15,3,3,4,2) | -1.65 nocturnal voids | Standard Deviation 0.916 |
| Desmopressin Melt 25 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 57 (n=86,85,78,81,17,24,21,16) | -1.50 nocturnal voids | Standard Deviation 1.156 |
| Desmopressin Melt 25 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 113 (n=53,56,49,47,11,15,13,11) | -1.65 nocturnal voids | — |
| Desmopressin Melt 50 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 29 (n=104,100,93,104,22,28,27,22) | -1.47 nocturnal voids | Standard Deviation 1.08 |
| Desmopressin Melt 50 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 57 (n=86,85,78,81,17,24,21,16) | -1.74 nocturnal voids | Standard Deviation 1.036 |
| Desmopressin Melt 50 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 113 (n=53,56,49,47,11,15,13,11) | -1.95 nocturnal voids | Standard Deviation 1.088 |
| Desmopressin Melt 50 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 169 (n=17,15,17,15,3,3,4,2) | -1.76 nocturnal voids | Standard Deviation 0.801 |
| Desmopressin Melt 100 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 169 (n=17,15,17,15,3,3,4,2) | -1.78 nocturnal voids | Standard Deviation 0.192 |
| Desmopressin Melt 100 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 113 (n=53,56,49,47,11,15,13,11) | -0.76 nocturnal voids | Standard Deviation 0.87 |
| Desmopressin Melt 100 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 57 (n=86,85,78,81,17,24,21,16) | -1.08 nocturnal voids | Standard Deviation 0.618 |
| Desmopressin Melt 100 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 29 (n=104,100,93,104,22,28,27,22) | -1.20 nocturnal voids | Standard Deviation 0.912 |
| Placebo to 25 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 169 (n=17,15,17,15,3,3,4,2) | -2.00 nocturnal voids | Standard Deviation 2 |
| Placebo to 25 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 113 (n=53,56,49,47,11,15,13,11) | -1.67 nocturnal voids | Standard Deviation 1.039 |
| Placebo to 25 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 57 (n=86,85,78,81,17,24,21,16) | -1.53 nocturnal voids | Standard Deviation 1.183 |
| Placebo to 25 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 29 (n=104,100,93,104,22,28,27,22) | -1.19 nocturnal voids | Standard Deviation 1.215 |
| Placebo to 50 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 169 (n=17,15,17,15,3,3,4,2) | -2.33 nocturnal voids | Standard Deviation 0.272 |
| Placebo to 50 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 29 (n=104,100,93,104,22,28,27,22) | -1.00 nocturnal voids | Standard Deviation 1.14 |
| Placebo to 50 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 113 (n=53,56,49,47,11,15,13,11) | -1.21 nocturnal voids | Standard Deviation 1.085 |
| Placebo to 50 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 57 (n=86,85,78,81,17,24,21,16) | -1.03 nocturnal voids | Standard Deviation 1.264 |
| Placebo to 100 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 57 (n=86,85,78,81,17,24,21,16) | -1.35 nocturnal voids | Standard Deviation 1.363 |
| Placebo to 100 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 113 (n=53,56,49,47,11,15,13,11) | -1.76 nocturnal voids | Standard Deviation 1.193 |
| Placebo to 100 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 169 (n=17,15,17,15,3,3,4,2) | -2.50 nocturnal voids | Standard Deviation 1.179 |
| Placebo to 100 μg | Part II: Change From Baseline in Mean Number of Nocturnal Voids to Days 29, 57, 113 and 169 | Day 29 (n=104,100,93,104,22,28,27,22) | -1.58 nocturnal voids | Standard Deviation 1.169 |
Secondary
Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II
A treatment-emergent adverse event (AE) was any AE occurring during the treatment period or a pretreatment AE that worsened in intensity during the treatment period. The treatment period was the period during which a subject received investigational medicinal product. If a subject discontinued the investigational medicinal product, the date of last dose was the last day of the treatment period.
Time frame: Week 5 up to Day 169
Population: Part II Safety Population includes study participants who received study intervention and had at least one safety assessment during study Part II.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Serious AEs | 3 participants |
| Placebo | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Adverse Drug Reactions | 64 participants |
| Placebo | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | All AEs | 95 participants |
| Placebo | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Deaths | 0 participants |
| Placebo | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Severe AEs | 7 participants |
| Placebo | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | AEs leading to discontinuation | 3 participants |
| Desmopressin Melt 10 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | All AEs | 95 participants |
| Desmopressin Melt 10 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | AEs leading to discontinuation | 3 participants |
| Desmopressin Melt 10 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Deaths | 0 participants |
| Desmopressin Melt 10 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Adverse Drug Reactions | 59 participants |
| Desmopressin Melt 10 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Severe AEs | 4 participants |
| Desmopressin Melt 10 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Serious AEs | 1 participants |
| Desmopressin Melt 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | AEs leading to discontinuation | 2 participants |
| Desmopressin Melt 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Serious AEs | 0 participants |
| Desmopressin Melt 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Severe AEs | 9 participants |
| Desmopressin Melt 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Adverse Drug Reactions | 58 participants |
| Desmopressin Melt 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | All AEs | 92 participants |
| Desmopressin Melt 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Deaths | 0 participants |
| Desmopressin Melt 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | All AEs | 100 participants |
| Desmopressin Melt 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Severe AEs | 5 participants |
| Desmopressin Melt 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Adverse Drug Reactions | 68 participants |
| Desmopressin Melt 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Deaths | 0 participants |
| Desmopressin Melt 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Serious AEs | 2 participants |
| Desmopressin Melt 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | AEs leading to discontinuation | 4 participants |
| Desmopressin Melt 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Severe AEs | 1 participants |
| Desmopressin Melt 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Deaths | 0 participants |
| Desmopressin Melt 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Adverse Drug Reactions | 10 participants |
| Desmopressin Melt 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | All AEs | 20 participants |
| Desmopressin Melt 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | AEs leading to discontinuation | 1 participants |
| Desmopressin Melt 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Serious AEs | 0 participants |
| Placebo to 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | AEs leading to discontinuation | 2 participants |
| Placebo to 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | All AEs | 27 participants |
| Placebo to 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Deaths | 0 participants |
| Placebo to 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Serious AEs | 0 participants |
| Placebo to 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Adverse Drug Reactions | 16 participants |
| Placebo to 25 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Severe AEs | 3 participants |
| Placebo to 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Severe AEs | 2 participants |
| Placebo to 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Deaths | 0 participants |
| Placebo to 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Serious AEs | 2 participants |
| Placebo to 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | All AEs | 25 participants |
| Placebo to 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Adverse Drug Reactions | 15 participants |
| Placebo to 50 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | AEs leading to discontinuation | 2 participants |
| Placebo to 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | AEs leading to discontinuation | 5 participants |
| Placebo to 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Serious AEs | 2 participants |
| Placebo to 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Adverse Drug Reactions | 18 participants |
| Placebo to 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Severe AEs | 1 participants |
| Placebo to 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | Deaths | 0 participants |
| Placebo to 100 μg | Part II: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part II | All AEs | 28 participants |
Secondary
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
Part II outcomes tested the durability of the effect observed in Part I. Percentage of participants in each treatment arm that had a greater than 33% reduction from baseline to Days 29, 57, 113 and 169 in mean number of nocturnal voids. Nocturnal void data were recorded in participant diaries.
Time frame: - Week 3 to Day 1 (Baseline), Days 29, 57, 113 and 169
Population: Observed Cases (OC) Analysis Set which consisted of participants who had information on mean number of nocturnal voids for both the screening visit and the final visit in Part I (Day 28) and did not have any major protocol deviations. Participants had data representing the visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 | Day 29 (n=104,100,93,104,22,28,27,22) | 57 percentage of participants |
| Placebo | 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 | Day 57 (n=86,85,78,81,17,24,21,16) | 59 percentage of participants |
| Placebo | 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 | Day 113 (n=53,56,49,47,11,15,13,11) | 58 percentage of participants |
| Placebo | 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 | Day 169 (n=17,15,17,15,3,3,4,2) | 61 percentage of participants |
| Desmopressin Melt 10 μg | 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 | Day 169 (n=17,15,17,15,3,3,4,2) | 80 percentage of participants |
| Desmopressin Melt 10 μg | 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 | Day 57 (n=86,85,78,81,17,24,21,16) | 68 percentage of participants |
| Desmopressin Melt 10 μg | 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 | Day 29 (n=104,100,93,104,22,28,27,22) | 64 percentage of participants |
| Desmopressin Melt 10 μg | 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 | Day 113 (n=53,56,49,47,11,15,13,11) | 79 percentage of participants |
| Desmopressin Melt 25 μg | 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 | Day 29 (n=104,100,93,104,22,28,27,22) | 68 percentage of participants |
| Desmopressin Melt 25 μg | 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 | Day 169 (n=17,15,17,15,3,3,4,2) | 76 percentage of participants |
| Desmopressin Melt 25 μg | 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 | Day 57 (n=86,85,78,81,17,24,21,16) | 71 percentage of participants |
| Desmopressin Melt 25 μg | 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 | Day 113 (n=53,56,49,47,11,15,13,11) | 69 percentage of participants |
| Desmopressin Melt 50 μg | 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 | Day 29 (n=104,100,93,104,22,28,27,22) | 68 percentage of participants |
| Desmopressin Melt 50 μg | 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 | Day 57 (n=86,85,78,81,17,24,21,16) | 83 percentage of participants |
| Desmopressin Melt 50 μg | 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 | Day 113 (n=53,56,49,47,11,15,13,11) | 87 percentage of participants |
| Desmopressin Melt 50 μg | 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 | Day 169 (n=17,15,17,15,3,3,4,2) | 87 percentage of participants |
| Desmopressin Melt 100 μg | 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 | Day 169 (n=17,15,17,15,3,3,4,2) | 100 percentage of participants |
| Desmopressin Melt 100 μg | 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 | Day 113 (n=53,56,49,47,11,15,13,11) | 55 percentage of participants |
| Desmopressin Melt 100 μg | 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 | Day 57 (n=86,85,78,81,17,24,21,16) | 41 percentage of participants |
| Desmopressin Melt 100 μg | 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 | Day 29 (n=104,100,93,104,22,28,27,22) | 73 percentage of participants |
| Placebo to 25 μg | 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 | Day 169 (n=17,15,17,15,3,3,4,2) | 67 percentage of participants |
| Placebo to 25 μg | 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 | Day 113 (n=53,56,49,47,11,15,13,11) | 73 percentage of participants |
| Placebo to 25 μg | 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 | Day 57 (n=86,85,78,81,17,24,21,16) | 71 percentage of participants |
| Placebo to 25 μg | 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 | Day 29 (n=104,100,93,104,22,28,27,22) | 43 percentage of participants |
| Placebo to 50 μg | 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 | Day 169 (n=17,15,17,15,3,3,4,2) | 100 percentage of participants |
| Placebo to 50 μg | 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 | Day 29 (n=104,100,93,104,22,28,27,22) | 48 percentage of participants |
| Placebo to 50 μg | 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 | Day 113 (n=53,56,49,47,11,15,13,11) | 54 percentage of participants |
| Placebo to 50 μg | 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 | Day 57 (n=86,85,78,81,17,24,21,16) | 43 percentage of participants |
| Placebo to 100 μg | 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 | Day 57 (n=86,85,78,81,17,24,21,16) | 69 percentage of participants |
| Placebo to 100 μg | 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 | Day 113 (n=53,56,49,47,11,15,13,11) | 73 percentage of participants |
| Placebo to 100 μg | 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 | Day 169 (n=17,15,17,15,3,3,4,2) | 100 percentage of participants |
| Placebo to 100 μg | 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 | Day 29 (n=104,100,93,104,22,28,27,22) | 73 percentage of participants |
Secondary
Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I
A treatment-emergent adverse event (AE) was any AE occurring during the treatment period or a pretreatment AE that worsened in intensity during the treatment period. The treatment period was the period during which a subject received investigational medicinal product. If a subject discontinued the investigational medicinal product, the date of last dose was the last day of the treatment period.
Time frame: Day 1 up to Week 4 (end of Part I)
Population: Part I Safety Population includes study participants who received study intervention and had at least one safety assessment during study Part I.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Serious AEs | 1 participants |
| Placebo | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | AEs leading to discontinuation | 8 participants |
| Placebo | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Deaths | 0 participants |
| Placebo | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Severe AEs | 4 participants |
| Placebo | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | All AEs | 94 participants |
| Placebo | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Adverse drug reactions (ADRs) | 62 participants |
| Desmopressin Melt 10 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Adverse drug reactions (ADRs) | 62 participants |
| Desmopressin Melt 10 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Serious AEs | 2 participants |
| Desmopressin Melt 10 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Severe AEs | 8 participants |
| Desmopressin Melt 10 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Deaths | 0 participants |
| Desmopressin Melt 10 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | AEs leading to discontinuation | 6 participants |
| Desmopressin Melt 10 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | All AEs | 100 participants |
| Desmopressin Melt 25 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | AEs leading to discontinuation | 2 participants |
| Desmopressin Melt 25 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Severe AEs | 5 participants |
| Desmopressin Melt 25 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | All AEs | 98 participants |
| Desmopressin Melt 25 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Adverse drug reactions (ADRs) | 61 participants |
| Desmopressin Melt 25 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Deaths | 0 participants |
| Desmopressin Melt 25 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Serious AEs | 1 participants |
| Desmopressin Melt 50 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Serious AEs | 2 participants |
| Desmopressin Melt 50 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | All AEs | 103 participants |
| Desmopressin Melt 50 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Deaths | 0 participants |
| Desmopressin Melt 50 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | AEs leading to discontinuation | 13 participants |
| Desmopressin Melt 50 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Severe AEs | 13 participants |
| Desmopressin Melt 50 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Adverse drug reactions (ADRs) | 73 participants |
| Desmopressin Melt 100 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Severe AEs | 7 participants |
| Desmopressin Melt 100 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Deaths | 0 participants |
| Desmopressin Melt 100 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | All AEs | 110 participants |
| Desmopressin Melt 100 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Serious AEs | 0 participants |
| Desmopressin Melt 100 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | AEs leading to discontinuation | 13 participants |
| Desmopressin Melt 100 μg | Part I: Participants With Treatment-Emergent Adverse Events (AEs) During Study Part I | Adverse drug reactions (ADRs) | 80 participants |