A Trial to Investigate Efficacy, Safety and Tolerability of FE 201836 for Nocturia Due to Nocturnal Polyuria in Adults

Nocturia Clinical Trial

Official title:

A Randomised, Double-blind, Placebo-controlled, Response-adaptive Dose-finding Trial Investigating the Efficacy, Safety and Tolerability of Oral Doses of FE 201836, With Desmopressin Orally Disintegrating Tablet as a Benchmark, During 12 Weeks of Treatment for Nocturia Due to Nocturnal Polyuria in Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03201419
• Other study ID #: 000233
• Secondary ID: 2016-003851-31
• Status: Completed
• Phase: Phase 2
• Start date: July 27, 2017
• Est. completion date: October 31, 2019

Study information

• Verified date: October 2020
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial was to investigate the efficacy, safety and tolerability of different oral doses of FE 201836, with desmopressin as a benchmark, during 12 weeks of treatment for nocturia due to nocturnal polyuria in adults

Recruitment information / eligibility

• Status: Completed
• Enrollment: 302
• Est. completion date: October 31, 2019
• Est. primary completion date: October 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults =18 years of age (at the time of written consent)

• Medical history of, or subject reported nocturia symptoms during the 6 months prior to Visit 1

• =2 nocturnal voids (an average over 3 days) as documented in the 3-day e-Diary prior to Visit 2

• The largest single voided volume must be =200 mL (at least 1 void =200 mL) as documented in the 3-day e-Diary prior to Visit 2

• Nocturnal polyuria, defined as Nocturnal Polyuria index >33%, a ratio of Nocturnal Urine Volume in excess of 33% of total daily (24-hour) urine volume as documented in the 3-day e-Diary prior to Visit 2

• =20% decrease in the nocturnal diuresis rate (mL/min) (that was recorded at Visit 2) as documented in the 3-day e-Diary prior to Visit 3

Exclusion Criteria:

• Current diagnosis of Obstructive Sleep Apnoea (OSA)

• Restless Legs Syndrome (RLS)

• Bladder Outlet Obstruction (BOO) or urine flow <5 mL/s, as confirmed by uroflowmetry upon suspicion during screening prior to Visit 2

• 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)

• Any pelvic or lower urinary tract surgery and/or radio therapy or previous pelvic irradiation within the past 6 months prior to Visit 1. Including e.g., transurethral resection for Bladder Outlet Obstruction or Benign Prostatic Hyperplasia, hysterectomy or female incontinence procedures

• 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, chronic pelvic pain syndrome, or stone in the bladder or urethra causing symptoms

• A history of cancer with the last date of disease activity/presence of malignancy within the last 12 months prior to Visit 1, except for adequately treated basal cell carcinoma of the skin

• History of any neurological disease affecting bladder function or muscle strength (e.g., Multiple Sclerosis, Parkinson's, spinal cord injury, spina bifida)

• Habitual (fluid intake >3L per day) or psychogenic polydipsia

• Uncontrolled hypertension, as judged by the investigator

• Uncontrolled diabetes mellitus, as judged by the investigator

• Central or nephrogenic diabetes insipidus

• Known history of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion

• History of gastric retention

• Suspicion or evidence of congestive heart failure, (New York Heart Association (NYHA) class II, III, IV)

• Hyponatraemia:

• Serum sodium level <135 mmol/L at Visit 1(re-tested, with results available within 7 days)

• Serum sodium level <130 mmol/L at Visit 3 (re-tested, with results available within 7 days)

• Use of any prohibited therapy listed below:

• Current or former (within 3 months prior to screening) treatment with any other investigational medicinal product (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

• Antiarrhythmic agents

• V2-receptor antagonists/agonists (e.g., vaptans/desmopressin, vasopressin)

• Loperamide

• Botulinum toxin (cosmetic non-urological use is acceptable)

• Valproate

Related Conditions & MeSH terms

• Nocturia
• Polyuria

Intervention

Drug:
• FE 201836
Oral solution for daily intake
• Desmopressin
Desmopressin Orally Disintegrating Tablet (ODT)
• Placebo oral solution
Manufactured to mimic experimental drug
• Placebo ODT
Manufactured to mimic experimental drug

Locations

Country	Name	City	State
Belgium	ULB Hopital Erasme	Bruxelles
Belgium	UZ Antwerpen	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	AZ Groeninge - Campus Vercruysselaan	Kortrijk
Belgium	UZ Leuven	Leuven
Canada	Milestone Research	London
Canada	SKDS Research Inc.	Newmarket
Canada	Ultra-Med Inc.	Pointe-Claire	Quebec
Canada	DIEX Recherche Quebec Inc.	Quebec
Canada	Clinique Médicale St-Louis (Recherche) inc d/b/a/ Centre de Recherche Saint-Louis	Québec
Canada	Bluewater Health-Norman Site	Sarnia
Canada	CHUS - Hôpital Fleurimont	Sherbrooke
Canada	DIEX Recherche Sherbrooke Inc.	Sherbrooke
Canada	Ferring Investigational Site	Toronto
Canada	DIEX Recherche Victoriaville Inc.	Victoriaville
Czechia	Urologie Benešov - Afimed s.r.o.	Benešov
Czechia	Fakultni nemocnice Brno, Dept of Klinika nemoci plicnich a tuberkulozy	Brno
Czechia	Krajska nemocnice Liberec, a.s.	Liberec
Czechia	Urocentrum Plzen	Plzen
Czechia	Thomayerova nemocnice, PARENT	Praha
Germany	Gemeinschaftspraxis fuer Urologie und Andrologie	Duisburg
Germany	Urologische Gemeinschaftspraxis	Emmendingen
Germany	Klinikum Weiden, Klinik f. Urologie, Andrologie und Kinderurologie	Weiden
Hungary	Jahn Ferenc Del-pesti Korhaz es Rendelointezet	Budapest
Hungary	Synexus Magyarorszag Kft.	Budapest
Hungary	Bagoly Egeszseghaz	Kecskemet
Hungary	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz Urologia	Nyiregyhaza
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet	Szolnok
Poland	Nasz Lekarz Osrodek Badan Klinicznych	Bydgoszcz
United States	South Florida Medical Research	Aventura	Florida
United States	American Health Network of Indiana, LLC	Avon	Indiana
United States	Achieve Clinical Research, LLC	Birmingham	Alabama
United States	American Health Research, Inc.	Charlotte	North Carolina
United States	Tampa Bay Medical Research, Inc.	Clearwater	Florida
United States	Women's Medical Research Group, LLC	Clearwater	Florida
United States	Ericksen Research & Development, LLC	Clinton	Utah
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Downtown Women's Health Care	Denver	Colorado
United States	Genitourinary Surgical Consultants, P.C.	Denver	Colorado
United States	HWC Women's Research Center	Englewood	Ohio
United States	Finlay Medical Research Corp	Greenacres City	Florida
United States	American Health Network of Indiana, LLC	Greenfield	Indiana
United States	Medication Management, LLC	Greensboro	North Carolina
United States	Peters Medical Research	High Point	North Carolina
United States	MCA Research - Partner	Houston	Texas
United States	Beyer Research	Kalamazoo	Michigan
United States	Clinical Research Consortium, an AMR company	Las Vegas	Nevada
United States	Clinical Trials Research	Lincoln	California
United States	Doctors Research Institute Corporation	Miami	Florida
United States	Pharmax Research Clinic	Miami	Florida
United States	Sanitas Research	Miami	Florida
United States	Coastal Clinical Research, an AMR company	Mobile	Alabama
United States	Coastal Carolina Research Center, Inc	Mount Pleasant	South Carolina
United States	PMG Research of Charleston, LLC	Mount Pleasant	South Carolina
United States	Tri Valley Urology Medical Group	Murrieta	California
United States	Bayside Clinical Research LLC	New Port Richey	Florida
United States	Mid Hudson Medical Research, PLLC	New Windsor	New York
United States	Clinical Research Associates of Tidewater, an AMR company	Norfolk	Virginia
United States	Advanced Research Institute	Ogden	Utah
United States	Quality Clinical Research Center, Inc.	Omaha	Nebraska
United States	Pines Care Research Center, Inc	Pembroke Pines	Florida
United States	Clinical Research Center of Florida	Pompano Beach	Florida
United States	Premier Medical Group of the Hudson Valley, PC	Poughkeepsie	New York
United States	NECCR Primacare Research, LLC	Providence	Rhode Island
United States	PMG Research of Raleigh, LLC	Raleigh	North Carolina
United States	Remedica LLC	Rochester	Michigan
United States	Meridien Research, Inc.	Saint Petersburg	Florida
United States	San Diego Clinical Trials	San Diego	California
United States	Bay State Clinical Trials, Inc.	Watertown	Massachusetts
United States	Advanced Rx Clinical Research Group, Inc.	Westminster	California
United States	PMG Research of Wilmington, LLC	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Germany,  Hungary,  Poland, 

References & Publications (1)

Hudgens S, Howerter A, Polek E, Andersson FL. Psychometric validation and interpretation of the Nocturia Impact Diary in a clinical trial setting. Qual Life Res. 2021 Dec 21. doi: 10.1007/s11136-021-03060-4. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment	Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.; The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits.; Level estimated for baseline value of mean number of nocturnal voids equal to 2, and 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval are presented in this endpoint.	Baseline, during 12 weeks of treatment
Secondary	Change From Baseline in Mean Number of Nocturnal Voids at Week 1	Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.; The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.; MMRM=Mixed Model for Repeated Measurements.; For all visit-specific results, the tables present the number of subjects with an observation of the endpoints in question at the specific visit. All secondary analyses are performed using the observed-case approach based on repeated measurements for all subjects in the ITT-RT population. That is, these secondary analyses are based on all subjects with at least one non-missing post-baseline observation (with a baseline value if relevant).	Baseline, Week 1
Secondary	Change From Baseline in Mean Number of Nocturnal Voids at Week 4	Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.; The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.	Baseline, Week 4
Secondary	Change From Baseline in Mean Number of Nocturnal Voids at Week 8	Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.; The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.	Baseline, Week 8
Secondary	Change From Baseline in Mean Number of Nocturnal Voids at Week 12	Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning.; The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2.	Baseline, Week 12
Secondary	Responder Rate in Nocturnal Voids at Week 1	Defined as 50% reduction in nocturnal voids from baseline.; Adjusted visit-specific estimated odds of at least 50% in the reduction mean number of nocturnal voids are estimated using a baseline value of 2.; The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).	Week 1
Secondary	Responder Rate in Nocturnal Voids at Week 4	Defined as 50% reduction in nocturnal voids from baseline.; Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2.; The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).	Week 4
Secondary	Responder Rate in Nocturnal Voids at Week 8	Defined as 50% reduction in nocturnal voids from baseline.; Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2.; The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).	Week 8
Secondary	Responder Rate in Nocturnal Voids at Week 12	Defined as 50% reduction in nocturnal voids from baseline.; Adjusted visit-specific estimated odds of at least 50% reduction in the mean number of nocturnal voids are estimated using a baseline value of 2.; The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).	Week 12
Secondary	Responder Rate in Nocturnal Voids During 12 Weeks of Treatment	Defined as 50% reduction in nocturnal voids from baseline.; Estimated odds of at least 50% reduction in the aggregated mean number of nocturnal voids for a subject with 2 nocturnal voids at baseline are presented in this endpoint.; The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.; The estimated odd equals the probability of response divided by the probability of non-response; these odds may vary between 0 and infinity. For example, if the probability of responding is 80%, the odd of responding is 4, as it is 4 times more likely to respond (80%) then it is not to respond (20%).	During 12 weeks of treatment
Secondary	Change From Baseline in Mean NI Diary Total Score at Week 1	The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall quality of life (QoL) impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items.Responses are scored from 0 to 4 (lowest t o highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).; The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.	Baseline, Week 1
Secondary	Change From Baseline in Mean NI Diary Total Score at Week 4	The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).; The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.	Baseline, Week 4
Secondary	Change From Baseline in Mean NI Diary Total Score at Week 8	The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).; The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.	Baseline, Week 8
Secondary	Change From Baseline in Mean NI Diary Total Score at Week 12	The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).; The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40.	Baseline, Week 12
Secondary	Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment	The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardized from 0 to 100 (lowest to highest impact).; The score at each visit was calculated as the mean over the three consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits.; Level estimated for baseline value of mean NI Diary Total Score equal to 40 is presented in this endpoint.; The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.	Baseline, during 12 weeks of treatment
Secondary	Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment	The percentages of nights during the treatment period with at most one nocturnal void are presented in this endpoint.; Level estimated for baseline value of mean number of nocturnal voids equal to 2 is presented in this endpoint.	During 12 weeks of treatment
Secondary	Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment	The percentages of nights during the treatment period with complete response, i.e. no nocturnal voids are presented in this endpoint.; Level estimated for baseline value of mean number of nocturnal voids equal to 2 is presented in this endpoint.	During 12 weeks of treatment
Secondary	Change From Baseline in Mean NI Diary Overall Impact Score at Week 1	The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).; The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.	Baseline, Week 1
Secondary	Change From Baseline in Mean NI Diary Overall Impact Score at Week 4	The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).; The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.	Baseline, Week 4
Secondary	Change From Baseline in Mean NI Diary Overall Impact Score at Week 8	The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).; The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.	Baseline, Week 8
Secondary	Change From Baseline in Mean NI Diary Overall Impact Score at Week 12	The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).; The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40.	Baseline, Week 12
Secondary	Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment	The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardized from 0 to 100 (lowest to highest impact).; The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits.; Level estimated for baseline value of mean NI Diary Overall Impact Score equal to 40 is presented in this endpoint.; The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.	Baseline, during 12 weeks of treatment
Secondary	Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1	The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).; Visit-specific PGI-I in urinary symptoms is presented in this endpoint.	Week 1
Secondary	Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4	The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).; Visit-specific PGI-I in urinary symptoms is presented in this endpoint.	Week 4
Secondary	Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8	The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).; Visit-specific PGI-I in urinary symptoms is presented in this endpoint.	Week 8
Secondary	Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12	The PGI-I is a 1-item questionnaire designed to assess the patient's impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse).; Visit-specific PGI-I in urinary symptoms is presented in this endpoint.	Week 12
Secondary	Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1	The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).; Change from baseline in visit-specific PGI-S is presented in this endpoint.; Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.	Baseline, Week 1
Secondary	Change From Baseline in PGI-S Scores at Week 4	The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).; Change from baseline in visit-specific PGI-S is presented in this endpoint.; Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.	Baseline, Week 4
Secondary	Change From Baseline in PGI-S Scores at Week 8	The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).; Change from baseline in visit-specific PGI-S is presented in this endpoint.; Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.	Baseline, Week 8
Secondary	Change From Baseline in PGI-S Scores at Week 12	The PGI-S is a 1-item questionnaire designed to assess patient's impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe).; Change from baseline in visit-specific PGI-S is presented in this endpoint.; Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint.	Baseline, Week 12
Secondary	Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1	The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).; Change from baseline in visit-specific Hsu Bother is presented in this endpoint.; Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.	Baseline, Week 1
Secondary	Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4	The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).; Change from baseline in visit-specific Hsu Bother is presented in this endpoint.; Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.	Baseline, Week 4
Secondary	Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8	The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).; Change from baseline in visit-specific Hsu Bother is presented in this endpoint.; Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.	Baseline, Week 8
Secondary	Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12	The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely).; Change from baseline in visit-specific Hsu Bother is presented in this endpoint.; Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint.	Baseline, Week 12
Secondary	Change From Baseline in ISI at Week 4	The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia).; Change from baseline in visit-specific ISI is presented in this endpoint.; Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.	Baseline, Week 4
Secondary	Change From Baseline in ISI at Week 8	The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia).; Change from baseline in visit-specific ISI is presented in this endpoint.; Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.	Baseline, Week 8
Secondary	Change From Baseline in ISI at Week 12	The ISI is a 7-item questionnaire which comprises of four 'sleep-related' items and three 'wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia).; Change from baseline in visit-specific ISI is presented in this endpoint.; Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.	Baseline, Week 12
Secondary	Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1	The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occured.; The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).	Baseline, Week 1
Secondary	Change From Baseline in Mean Duration of FUSP at Week 4	The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.; The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).	Baseline, Week 4
Secondary	Change From Baseline in Mean Duration of FUSP at Week 8	The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.; The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).	Baseline, Week 8
Secondary	Change From Baseline in Mean Duration of FUSP at Week 12	The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.; The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min).	Baseline, Week 12
Secondary	Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment	The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred.; The visit-specific means were aggregated into a mean of current and preceding visits.; Level estimated for baseline value of mean duration of FUSP (minutes) equal to 180 is presented in this endpoint.; The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint.	Baseline, During 12 Weeks of Treatment
Secondary	Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1	The nocturnal diuresis rate (mL/min) is calculated as the mean of the nocturnal diuresis for each of the three nights, with the single-night nocturnal diuresis calculated as the ratio of NUV to total time in bed.; Change from baseline in visit-specific mean nocturnal diuresis (mL/min) is presented.; Level estimated for baseline value of mean nocturnal diuresis (mL/min) equal to 1.3 is presented in this endpoint.	Baseline, Week 1
Secondary	Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12	The nocturnal diuresis rate (mL/min) is calculated as the mean of the nocturnal diuresis for each of the three nights, with the single-night nocturnal diuresis calculated as the ratio of NUV to total time in bed.; Change from baseline in visit-specific mean nocturnal diuresis (mL/min) is presented.; Level estimated for baseline value of mean nocturnal diuresis (mL/min) equal to 1.3 is presented in this endpoint.	Baseline, Week 12
Secondary	Change From Baseline in Mean NUV in Week 1	The NUV is defined as the total urine volume from 5 minutes after bedtime with the intention to sleep including the first void within 30 minutes of rising in the morning.; The NUV at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NUV are estimated using a baseline value of 750 (mL).	Baseline, Week 1
Secondary	Change From Baseline in Mean NUV at Week 12	The NUV is defined as the total urine volume from 5 minutes after bedtime with the intention to sleep including the first void within 30 minutes of rising in the morning.; The NUV at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NUV are estimated using a baseline value of 750 (mL).	Baseline, Week 12