Clinical Trial Results:
A Double-blind, Randomised, Parallel-group Trial Investigating Sleep Behaviour and Daytime Performance in Nocturia Patients Treated with Desmopressin Orally Disintegrating Tablets as compared to Placebo.
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Summary
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EudraCT number |
2012-004388-34 |
Trial protocol |
GB |
Global end of trial date |
01 Jun 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Mar 2016
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First version publication date |
18 Jul 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
000088
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01779466 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Ferring Pharmaceuticals A/S
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Sponsor organisation address |
Kay Fiskers Plads 11, Copenhagen S, Denmark, 2300
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Public contact |
Clinical Development Support, Ferring Pharmaceuticals, DK0-Disclosure@ferring.com
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Scientific contact |
Clinical Development Support, Ferring Pharmaceuticals, DK0-Disclosure@ferring.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Jul 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Jun 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Jun 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Efficacy Objectives
• To investigate the relationship between nocturia, sleep, and daytime performance
• To investigate the efficacy of desmopressin orally disintegrating tablets (50 µg in men and 25 µg in women) versus placebo for treatment of patients with nocturia with respect to nocturia, sleep, and daytime performance.
Safety Objective
• To confirm the safety of desmopressin orally disintegrating tablets (50 µg in men and 25 µg in women) in the treatment of nocturia.
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Protection of trial subjects |
Subjects were fully informed of all pertinent aspects of the clinical trial including the possibility to discontinue at any time in language and terms appropriate for the patient and considering the local culture. Collected personal data and human biological samples were processed in compliance with the Declaration of Helsinki and its amendments in force at the initiation of the trial in compliance with the approved protocol and its amendments, Good Clinical Practice (GCP) and applicable regulatory requirements.
For safety reasons, serum sodium levels were monitored at regular intervals and a patient was to be withdrawn from the trial if the serum sodium level was ≤125 mmol/L or had any other sign of fluid overload such as peripheral or pulmonary oedema at any time point during the trial.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
09 Apr 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 5
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Worldwide total number of subjects |
5
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EEA total number of subjects |
5
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted in United Kingdom between 09 Apr 2013 to 01 Jun 2014. Screening was stopped on 26 Feb 2014 due to poor recruitment. At that time, only five female subjects had been randomised. | |||||||||
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Pre-assignment
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Screening details |
The intent was to randomise eligible subjects to one of the three treatments: Placebo, Desmopressin 50 µg (for men), and Desmopressin 25 µg (for females). However, only five female subjects (three in Desmopressin 25 µg, two in Placebo) and no male subjects (Desmopressin 50 µg) could be enrolled in the trial. | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Assessor | |||||||||
Blinding implementation details |
Treatment was blinded throughout. Both active and placebo IMP were provided as round, white tablets, marked with a diamond shaped figure on one side.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Desmopressin 25 μg orally disintegrating tablets | |||||||||
Arm description |
Desmopressin 25 μg orally disintegrating tablets for sublingual administration in the strength of 25 μg – for women only | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Desmopressin 25 μg
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Investigational medicinal product code |
FE 992026
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Other name |
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Pharmaceutical forms |
Sublingual tablet
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Routes of administration |
Sublingual use
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Dosage and administration details |
Subjects had to take one orally disintegrating tablet each night, approximately one hour prior to bedtime, for the entire duration of the three-month treatment period. Patients were instructed to place the tablet under the tongue and not to chew or swallow the table. They were also advised to minimise fluid intake from two hours before bedtime until seven hours after.
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Arm title
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Placebo | |||||||||
Arm description |
Placebo (not active) orally disintegrating tablets for sublingual administration – for both men and women. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Sublingual tablet
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Routes of administration |
Sublingual use
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Dosage and administration details |
Patients had to take one orally disintegrating tablet each night, approximately one hour prior to bedtime, for the entire duration of the three-month treatment period. Patients were instructed to place the tablet under the tongue and not to chew or swallow the table. They were also advised to minimise fluid intake from two hours before bedtime until seven hours after.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Desmopressin 25 μg orally disintegrating tablets
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Reporting group description |
Desmopressin 25 μg orally disintegrating tablets for sublingual administration in the strength of 25 μg – for women only | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo (not active) orally disintegrating tablets for sublingual administration – for both men and women. | ||
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End point title |
Efficacy Endpoints [1] | |||||||||
End point description |
There was no efficacy evaluation.
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End point type |
Primary
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End point timeframe |
There was no efficacy evaluation.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No efficacy objectives/endpoints were analysed due to low number of subjects. |
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| Notes [2] - Efficacy not evaluated since only five females were enrolled. [3] - Efficacy not evaluated since only five females were enrolled. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Clinically significant laboratory results [4] | |||||||||
End point description |
Safety laboratory variables included clinical chemistry, haematology and urinalysis. The Investigator reviewed the laboratory results and documented whether the results were normal or abnormal, and whether results were clinically or not clinically significant.
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End point type |
Primary
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End point timeframe |
Blood and urine samples for the assessment of safety laboratory variables were taken at Visit 0 (Screening) and Visit 5, Day 3. An additional blood sample for the analysis and monitoring of serum sodium were taken at Visit 3.
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The safety assessments were only presented as patient data listings i.e., no statistical analyses was performed as only five female subjects were enrolled in the trial. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Clinically significant vital signs and physical examinations [5] | |||||||||
End point description |
Vitals: Diastolic and systolic blood pressure (mmHg) and pulse (beats per minute) were measured after resting for 5 minutes in a sitting position. Vital signs measurements outside normal ranges were to be assessed as “abnormal, not clinically significant” or “abnormal, clinically significant” by the Investigator. Any abnormal, clinically significant changes were to be reported as adverse events (AEs).
Physical examinations: Physical examinations were performed by the Investigator or a delegated medically licensed qualified Sub-investigator. Any abnormal, clinically significant changes was to be reported as AEs.
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End point type |
Primary
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End point timeframe |
Vitals (Blood pressure and pulse rate): Visit 0, each day of Visits 2, 3, 4 and 5.
Physical examinations:Visit 0 and Visit 5; Day 3.
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The safety assessments were only presented as patient data listings i.e., no statistical analyses was performed as only five female subjects were enrolled in the trial. |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
The Investigator monitored the condition of the patient throughout the trial from the time of obtaining informed consent until the last visit.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16
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Reporting groups
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Reporting group title |
Desmopressin 25 μg orally disintegrating tablets
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Reporting group description |
AEs are presented by-subject for one of the three subjects dosed with Desmopressin 25 μg orally disintegrating tablets. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
AEs are presented by-subject for one of the two subjects dosed with placebo orally disintegrating tablets. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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06 Sep 2013 |
Inclusion criteria updated to:
•Male or female patients, aged 25-65 years (in place of 35-65 years) at the time of written consent, who currently had a regular sleep/wake schedule with minimal daytime napping (in place of a regular daytime schedule)
•At least 2 nocturnal voids per night as judged by the Investigator during both 3-day diary periods
•A habitual time-in-bed period, attempting to sleep, of between 6.0 and 9.5 hours per night (based on screening diary [CSD] and actigraphy)
The exclusion criteria regarding stress incontinence was updated to only moderate or severe cases, as judged by the Investigator.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| The trial also included a third arm Desmopressin 50 µg orally disintegrating tablets for sublingual administration, for men only. However, no subjects could be enrolled in the arm, hence the details are not presented. | |||||||
