Clinical Trials Register

Summary
EudraCT Number:	2017-000808-22
Sponsor's Protocol Code Number:	000278
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-09-19
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2017-000808-22

A.3

Full title of the trial

An Open-label Trial Investigating the Association Between Nocturia and Sleep During 12 Weeks of Treatment with Desmopressin Orally Disintegrating Tablet (ODT) for Nocturia due to Nocturnal Polyuria in Adults

Nyílt vizsgálat a nocturia és az alvás összefüggésének vizsgálatára, nokturnális polyuria okozta túlzott éjszakai vizeletürítés dezmopresszin szájban oldódó tablettával történő 12 hetes kezelése során, felnőttek esetében.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Trial Investigating the Association Between Nocturia and Sleep
During 12 Weeks of Treatment with Desmopressin for Nocturia due to Nocturnal Polyuria in Adults

A.3.2

Name or abbreviated title of the trial where available

AWAKEN

A.4.1

Sponsor's protocol code number

000278

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Ferring Pharmaceuticals A/S
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Ferring Pharmaceuticals A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ferring Pharmaceuticals A/S
B.5.2	Functional name of contact point	Clinical Development Support
B.5.3	Address:
B.5.3.1	Street Address	Kay Fiskers Plads 11
B.5.3.2	Town/ city	Copenhagen
B.5.3.3	Post code	2300
B.5.3.4	Country	Denmark
B.5.6	E-mail	DK0-Disclosure@ferring.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	NOCDURNA
D.2.1.1.2	Name of the Marketing Authorisation holder	Ferring Lægemidler A/S
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Nocdurna 50 microgram oral lyophilisate
D.3.4	Pharmaceutical form	Oral lyophilisate
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DESMOPRESSIN ACETATE
D.3.9.1	CAS number	62357-86-2
D.3.9.4	EV Substance Code	SUB01597MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	NOCDURNA
D.2.1.1.2	Name of the Marketing Authorisation holder	Ferring Lægemidler A/S
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Nocdurna 25 microgram oral lyophilisate
D.3.4	Pharmaceutical form	Oral lyophilisate
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DESMOPRESSIN ACETATE
D.3.9.1	CAS number	62357-86-2
D.3.9.4	EV Substance Code	SUB01597MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Nocturia due to Nocturnal Polyuria

E.1.1.1

Medical condition in easily understood language

Frequent nocturnal voiding

E.1.1.2

Therapeutic area

Body processes [G] - Metabolic Phenomena [G03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10064016
E.1.2	Term	Nocturnal polyuria
E.1.2	System Organ Class	100000017861

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the association between changes in the number of nocturnal voids and change in Nocturia Sleep Quality Scale (NSQS) total score in adult subjects with nocturia due to Nocturnal Polyuria (NP)

E.2.2

Secondary objectives of the trial

- To assess the association between changes in Patient Global Impression of Severity (PGI-S) and change in Nocturia Sleep Quality Scale (NSQS) total score
- To assess the association between Patient Global Impression of Improvement (PGI-I) and change in NSQS total score
- To assess the association between change in First Undisturbed Sleep Period (FUSP) and change in NSQS total score
- To assess changes from baseline in NSQS total score
- To assess changes from baseline in PGI-S and Bother scales
- To assess PGI-I scores
- To assess changes from baseline in number of nocturnal voids
- To assess changes from baseline in FUSP

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent prior to performance of any trial-related activity
2. Adults ≥18 years of age (at the time of written consent)
3. Female subjects of child-bearing potential must be willing and able to use adequate contraception throughout the trial. Documentation of an acceptable effective method of contraception must be available. All pre- and perimenopausal subjects have to perform pregnancy tests. Amenorrhea of more than 12 months duration based on the reported date of the last menstrual period is sufficient documentation of post-menopausal status and does not require any pregnancy test
4. Medical history of, or subject reported nocturia symptoms during the 6 months prior to Visit 1
5. ≥2 nocturnal voids per night (an average over 3 days) as documented in the 3-day e-Diary prior to Visit 2
6. The largest single voided volume must be >250 mL (at least 1 void >250 mL) as documented in the 3-day e-Diary prior to Visit 2
7. Nocturnal polyuria, defined as NPi >33%, a ratio of Nocturnal Urine Volume (NUV) in excess of 33% of total daily (24-hour) urine volume as documented in the 3-day e-Diary prior to Visit 2
8. Bothered by nocturia as defined by an NI Diary Total Score of ≥10 points (raw score) as documented in the 3-day e-Diary prior to Visit 2

E.4

Principal exclusion criteria

1. Current diagnosis of Obstructive Sleep Apnoea (OSA). In case of no current diagnosis of OSA, high-risk subjects should be excluded as assessed by the STOP-Bang questionnaire at Visit 1
2. Restless Legs Syndrome (RLS)
3. Current mild to severe depression as assessed by a score of ≥14 on the Beck Depression Inventory-II (BDI-II) scale at Visit 1 or Visit 2
4. History or suspicion of moderate to severe Lower Urinary Tract Symptoms (LUTS) with or without Bladder Outlet Obstruction (BOO). In case of suspicion of moderate or severe LUTS with or without BOO, subjects should be excluded from the trial as follows:
- All subjects with a Post-void Residual (PVR) >150 mL, as confirmed by ultrasound during screening prior to Visit 2
- Male subjects who have International Prostate Symptom Score (IPSS) ≥13 points and urinary flow <5 mL/s, as confirmed by uroflowmetry during screening prior to Visit 2
5. Urinary incontinence defined as an average of >1 episode/day in the 3-day e-Diary prior to Visit 2 (occasional urge incontinence during daytime or at night on the way to void is not necessarily exclusionary)
6. Predominant daytime voiding dysfunction due to Overactive Bladder (OAB), at Visit 2, defined as:
Frequency (an average of >8 daytime voids per day during the 3-day diary period)
AND
≥1 daily urgency episode (the subject could not postpone voiding or the subject leaked before arriving to the toilet)
7. Any pelvic or lower urinary tract surgery and/or radiotherapy or previous pelvic irradiation within the past 6 months prior to Visit 1. Including e.g., transurethral resection for BOO or Benign Prostatic Hyperplasia (BPH), hysterectomy or female incontinence procedures
8. Genito-urinary tract pathology that can in the investigator’s opinion be responsible for urgency or urinary incontinence e.g., symptomatic or recurrent urinary tract infections, interstitial cystitis, bladder-related pain, or stone in the bladder or urethra causing symptoms
9. A history of cancer with the last date of disease activity/prescence of malignancy within the last 12 months prior to Visit 1, except for adequately treated basal cell carcinoma of the skin
10. History of any neurological disease affecting bladder function or muscle strength (e.g., Multiple Sclerosis, Parkinson’s, spinal cord injury, spina bifida)
11. Habitual (fluid intake >3L per day) or psychogenic polydipsia
12. Uncontrolled hypertension, as judged by the investigator
13. Uncontrolled diabetes mellitus, as judged by the investigator
14. Central or nephrogenic diabetes insipidus
15. Known history of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion
16. History of gastric retention
17. Known or suspected cardiac insufficiency or other conditions associated with fluid overload,
sufficient to require treatment with diuretics, including a history of such conditions
18. Hyponatraemia (serum sodium level <135 mmol/L) at Visit 1 (re-tested and confirmed, with
results available within 7 days)
19. Renal insufficiency (estimated glomerular filtration rate ≤60 mL/min)
20. Hepatic and/or biliary diseases:
- Child-Pugh Class A, B, or C
- Aspartate aminotransferase and/or alanine aminotransferase levels ≥2x the upper limit of normal range
- Total bilirubin level >1.5 mg/dL
21. Known history of hypersensitivity to desmopressin ODT
31. Use of any prohibited therapy listed below:
- Current or former (within 3 months prior to screening) treatment with any other IMP
- Unstable electrostimulation or behavioural bladder training program less than 3 months prior to screening (stable electrostimulation or behavioural bladder training program started at least 3 months before screening are acceptable)
- Thiazide diuretics
- V2-receptor antagonists/agonists (e.g., vaptans/desmopressin, vasopressin)
- Loperamide
- Botulinum toxin (cosmetic non-urological use is acceptable)
- Valproate
32. Subjects with a known history of type IIB or platelet-type (pseudo) von Willebrand's disease (because of the risk of platelet aggregation and thrombocytopenia).
33. Subjects with existing medical conditions, which lead to sodium losing states such as nausea, bulimia, anorexia nervosa, chronic vomiting, diarrhoea, adrenocortical insufficiency and salt losing nephropathies.

E.5 End points

E.5.1

Primary end point(s)

Pearson correlation coefficient between change from baseline to Week 12 in number of nocturnal voids and the Nocturia Sleep Quality Scale (NSQS) total score

E.5.1.1

Timepoint(s) of evaluation of this end point

please refer to section E.5.1

E.5.2

Secondary end point(s)

- Pearson correlation coefficient between change from baseline to Weeks 1, 4 and 8 in number of nocturnal voids and the Nocturia Sleep Quality Scale (NSQS) total score
- Pearson correlation coefficient between change from baseline to Weeks 1, 4, 8 and 12 in Patient Global Impression of Severity (PGI-S) and NSQS total score
- Pearson correlation coefficient between PGI-I scores and change from baseline to Weeks 1, 4, 8 and 12 in NSQS total score
- Pearson correlation coefficient between change from baseline to Weeks 1, 4, 8 and 12 in First Undisturbed Sleep Period (FUSP) and NSQS total score
- Change from baseline in NSQS total score at Weeks 1, 4, 8 and 12 and during 12 weeks of treatment
- Change from baseline in PGI-S scores at Weeks 1, 4, 8 and 12
- Change from baseline in Bother as measured by the Hsu 5-point Likert Bother Scale at Weeks 1, 4, 8 and 12
- PGI-I scores at Weeks 1, 4, 8 and 12
- Change from baseline in number of nocturnal voids during 12 weeks of treatment
- Change from baseline in FUSP during 12 weeks of treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

please refer to section E.5.2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

In the present trial, the association between nocturia and sleep will be investigated in adult subjects with nocturia due to Nocturnal Polyuria (NP) following treatment with desmopressin.
In addition, sleep-related changes in metabolic biomarkers will be explored.

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Czech Republic

Hungary

Netherlands

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Trial completion is defined as when the last subject has completed the last visit in the treatment period (Visit 6).

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

138

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None (Patients will receive local standard medical care after trial end)

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-11-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-11-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-07-13

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