Nocturnal Enuresis
Conditions
Brief summary
This is multi-center, randomized, placebo-controlled, parallel-group, double-blind, dose-escalating clinical trial designed to assess the efficacy and safety of desmopressin orally lyophilisate for the treatment of nocturnal enuresis with decreased nighttime urinary osmolality.
Interventions
DRUGDesmopressin
Desmopressin oral lyophilisate tablet, 120 μg or 240 μg, administered sublingually once a day 1½ hours before bedtime.
DRUGPlacebo
Placebo oral lyophilisate tablet was administered sublingually once a day 1½ hours before bedtime.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed nocturnal enuresis with reduced nighttime urinary osmolality * Age 6 or above but under 16 regardless of gender * Out-patient * Had 10 or more wet nights during the 14-day baseline period and at least 4 wet nights in each respective week * Deemed healthy by the investigator * Able to agree to and comply with fluid-intake restriction during the clinical trial and matters specified in the clinical trial protocol * Consent from the pediatric patient's legally acceptable representative * Demonstrate an understanding about this clinical trial after receiving an explanation corresponding to the prospective subject's intelligibility * Show no possibility of being a nursing mother or pregnant, or becoming pregnant * If under drug or medical therapy other than Desmopressin for treating nocturnal enuresis: able to discontinue such treatment
Exclusion criteria
* Suffer from enuresis with an underlying disease * Participated in another clinical trial within six months preceding consent * Used an intranasal Desmopressin in the past * Presently undergoing a systemic antibiotic treatment, a treatment with an antidiuretic or a drug that affects urinary concentration, or a drug or medical therapy for overactive bladder * Have an anomaly or a disease that may affect the oral absorption of drug products * Hard to get cooperation from subject by school refusal, punishment or bullying * Deemed by the investigator to be inappropriate to participate in this trial * Unable to be placed on water-intake restriction starting from two hours before bedtime * Evidence of hepatic, renal, cardiac, or pulmonary dysfunction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Number of Wet Nights Between Baseline and Treatment Period II | Baseline (14-day period prior to starting study treatment) and Treatment Period II (weeks 3-4 after treatment initiation). | The number of wet nights was recorded by participants (or their caregivers) in a daily diary. The difference was calculated from the number of wet nights during the 14-day Baseline Period minus the number of wet nights during the 14-day Treatment Period II. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Number of Wet Nights Between Baseline and Treatment Period I | Baseline (14-day period prior to starting study treatment) and Treatment Period I (weeks 1-2 after treatment initiation). | The number of wet nights was recorded by participants (or their caregivers) in a daily diary. The difference was calculated from the number of wet nights during the 14-day Baseline Period minus the number of wet nights during the 14-day Treatment Period I. |
| Change in Number of Wet Nights Between Treatment Periods I and II | Treatment Period I (weeks 1-2) and Treatment Period II (weeks 3-4) | The number of wet nights was recorded by participants (or their caregivers) in a daily diary. The difference was calculated from the number of wet nights during the 14-day Treatment Period I minus the number of wet nights during the 14-day Treatment Period II. |
Countries
Japan
Participant flow
Pre-assignment details
174 subjects consented and entered the 14-day screening period during which Baseline characteristics regarding enuretic episodes were established. Eligible patients who met the criterion were randomized 1:1 to receive either desmopressin or matching placebo. Randomization was stratified by gender, age and number of wet nights at Baseline.
Participants by arm
| Arm | Count |
|---|---|
| Desmopressin During treatment period I participants received 120 μg per day desmopressin oral lyophilisate tablet for 14 days. Participants for whom treatment was effective (a reduction of ≥ 75% from Baseline in the number of wet nights), and who showed no problems with tolerability, continued to receive the same treatment for a further 14 days in treatment period II. Participants for whom efficacy was inadequate (a reduction of \<75% from Baseline in the number of wet nights), but who showed no tolerability problems, received an increased dose of desmopressin oral lyophilisate tablet 240 µg for 14 days in treatment period II. | 45 |
| Placebo Participants received matching placebo tablets during treatment periods I and II according to the same efficacy criteria as participants in the Desmopressin treatment group. | 44 |
| Total | 89 |
Baseline characteristics
| Characteristic | Desmopressin | Placebo | Total |
|---|---|---|---|
| Age Continuous | 8.2 years STANDARD_DEVIATION 1.6 | 8.1 years STANDARD_DEVIATION 1.4 | 8.1 years STANDARD_DEVIATION 1.5 |
| Age, Customized 10 to15 years old | 9 participants | 8 participants | 17 participants |
| Age, Customized 6 to 9 years old | 36 participants | 36 participants | 72 participants |
| Body Mass Index (BMI) | 16.46 kg/m˄2 STANDARD_DEVIATION 2.47 | 16.43 kg/m˄2 STANDARD_DEVIATION 1.77 | 16.44 kg/m˄2 STANDARD_DEVIATION 2.14 |
| Height | 128.14 cm STANDARD_DEVIATION 11.3 | 127.68 cm STANDARD_DEVIATION 8.61 | 127.92 cm STANDARD_DEVIATION 10.01 |
| Number of Wet Nights during Baseline | 12.2 days STANDARD_DEVIATION 1.5 | 12.4 days STANDARD_DEVIATION 1.5 | 12.3 days STANDARD_DEVIATION 1.5 |
| Number of Wet Nights during Baseline by stratification criteria 10 to 13 wet nights | 32 participants | 30 participants | 62 participants |
| Number of Wet Nights during Baseline by stratification criteria 14 wet nights | 13 participants | 14 participants | 27 participants |
| Prior treatment of Nocturnal Enuresis with Drugs No prior treatment | 45 participants | 44 participants | 89 participants |
| Prior treatment of Nocturnal Enuresis with Drugs Prior treatment received | 0 participants | 0 participants | 0 participants |
| Prior treatment of Nocturnal Enuresis with Therapy No prior therapy | 0 participants | 0 participants | 0 participants |
| Prior treatment of Nocturnal Enuresis with Therapy Prior therapy | 45 participants | 44 participants | 89 participants |
| Region of Enrollment Japan | 45 participants | 44 participants | 89 participants |
| Sex: Female, Male Female | 17 Participants | 21 Participants | 38 Participants |
| Sex: Female, Male Male | 28 Participants | 23 Participants | 51 Participants |
| Weight | 27.59 kg STANDARD_DEVIATION 8.4 | 27.01 kg STANDARD_DEVIATION 5.32 | 27.30 kg STANDARD_DEVIATION 7.01 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 45 | 14 / 44 |
| serious Total, serious adverse events | 0 / 45 | 0 / 44 |
Outcome results
Primary
Change in the Number of Wet Nights Between Baseline and Treatment Period II
The number of wet nights was recorded by participants (or their caregivers) in a daily diary. The difference was calculated from the number of wet nights during the 14-day Baseline Period minus the number of wet nights during the 14-day Treatment Period II.
Time frame: Baseline (14-day period prior to starting study treatment) and Treatment Period II (weeks 3-4 after treatment initiation).
Population: The Full Analysis Set (FAS) included all participants who received at least one dose of study treatment, satisfied all the major eligibility criteria and for whom efficacy data was obtained.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Desmopressin | Change in the Number of Wet Nights Between Baseline and Treatment Period II | 3.264 wet nights |
| Placebo | Change in the Number of Wet Nights Between Baseline and Treatment Period II | 1.451 wet nights |
p-value: 0.00995% CI: [0.462, 3.163]ANCOVA
Secondary
Change in Number of Wet Nights Between Baseline and Treatment Period I
The number of wet nights was recorded by participants (or their caregivers) in a daily diary. The difference was calculated from the number of wet nights during the 14-day Baseline Period minus the number of wet nights during the 14-day Treatment Period I.
Time frame: Baseline (14-day period prior to starting study treatment) and Treatment Period I (weeks 1-2 after treatment initiation).
Population: The Full analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Desmopressin | Change in Number of Wet Nights Between Baseline and Treatment Period I | 2.946 wet nights |
| Placebo | Change in Number of Wet Nights Between Baseline and Treatment Period I | 1.317 wet nights |
p-value: 0.01895% CI: [0.287, 2.972]ANCOVA
Secondary
Change in Number of Wet Nights Between Treatment Periods I and II
The number of wet nights was recorded by participants (or their caregivers) in a daily diary. The difference was calculated from the number of wet nights during the 14-day Treatment Period I minus the number of wet nights during the 14-day Treatment Period II.
Time frame: Treatment Period I (weeks 1-2) and Treatment Period II (weeks 3-4)
Population: The full analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Desmopressin | Change in Number of Wet Nights Between Treatment Periods I and II | 0.318 wet nights |
| Placebo | Change in Number of Wet Nights Between Treatment Periods I and II | 0.135 wet nights |
p-value: 0.75295% CI: [-0.968, 1.335]ANCOVA