Nocturia
Conditions
Brief 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
Interventions
DRUGFE 201836
Oral solution for daily intake
DRUGDesmopressin
Desmopressin Orally Disintegrating Tablet (ODT)
Manufactured to mimic experimental drug
DRUGPlacebo ODT
Manufactured to mimic experimental drug
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Each subject will receive 2 medications (an oral solution and an orally disintegrating tablet (ODT) formulation) throughout the trial, in order to keep the treatment blinded.
Intervention model description
The trial consisted of a 2 week period of screening/lifestyle changes during which no treatment was given, a 2 week enrichment period (including a 1 week single blind active run-in period \[FE 201836 500 µg\] and a 1 week washout period) followed by a 12 week randomized treatment period for each subject. Prior to the first interim analysis, the first 129 subjects were randomized to daily treatment with FE 201836 500 µg, placebo, or desmopressin (25 µg for females and 50 µg for males) in a 2:2:1 ratio. After the first interim analysis, subjects were randomized to daily treatment with FE 201836 (50 µg, 100 µg, 150 µg, 250 µg, 350 µg, or 500 µg), placebo, or desmopressin (25 µg for females and 50 µg for males) using response adaptive allocation probabilities.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment | Baseline, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | Baseline, 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. |
| Change From Baseline in Mean Number of Nocturnal Voids at Week 8 | Baseline, 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. |
| Change From Baseline in Mean Number of Nocturnal Voids at Week 12 | Baseline, 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. |
| Responder Rate in Nocturnal Voids at Week 1 | 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%). |
| Responder Rate in Nocturnal Voids at Week 4 | 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%). |
| Responder Rate in Nocturnal Voids at Week 8 | 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%). |
| Responder Rate in Nocturnal Voids at Week 12 | 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%). |
| Responder Rate in Nocturnal Voids During 12 Weeks of Treatment | 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%). |
| Change From Baseline in Mean NI Diary Total Score at Week 1 | Baseline, 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. |
| Change From Baseline in Mean NI Diary Total Score at Week 4 | Baseline, 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. |
| Change From Baseline in Mean NI Diary Total Score at Week 8 | Baseline, 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. |
| Change From Baseline in Mean NI Diary Total Score at Week 12 | Baseline, 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. |
| Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment | Baseline, 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. |
| Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment | 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. |
| Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment | 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. |
| Change From Baseline in Mean NI Diary Overall Impact Score at Week 1 | Baseline, 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. |
| Change From Baseline in Mean NI Diary Overall Impact Score at Week 4 | Baseline, 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. |
| Change From Baseline in Mean NI Diary Overall Impact Score at Week 8 | Baseline, 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. |
| Change From Baseline in Mean NI Diary Overall Impact Score at Week 12 | Baseline, 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. |
| Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment | Baseline, 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. |
| Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1 | 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. |
| Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4 | 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. |
| Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8 | 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. |
| Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12 | 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. |
| Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1 | Baseline, 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. |
| Change From Baseline in PGI-S Scores at Week 4 | Baseline, 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. |
| Change From Baseline in PGI-S Scores at Week 8 | Baseline, 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. |
| Change From Baseline in PGI-S Scores at Week 12 | Baseline, 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. |
| Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1 | Baseline, 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. |
| Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4 | Baseline, 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. |
| Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8 | Baseline, 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. |
| Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12 | Baseline, 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. |
| Change From Baseline in ISI at Week 4 | Baseline, 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. |
| Change From Baseline in ISI at Week 8 | Baseline, 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. |
| Change From Baseline in ISI at Week 12 | Baseline, 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. |
| Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1 | Baseline, 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). |
| Change From Baseline in Mean Duration of FUSP at Week 4 | Baseline, 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). |
| Change From Baseline in Mean Duration of FUSP at Week 8 | Baseline, 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). |
| Change From Baseline in Mean Duration of FUSP at Week 12 | Baseline, 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). |
| Change From Baseline in Mean Number of Nocturnal Voids at Week 1 | Baseline, 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). |
| Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1 | Baseline, 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. |
| Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12 | Baseline, 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. |
| Change From Baseline in Mean NUV in Week 1 | Baseline, 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). |
| Change From Baseline in Mean NUV at Week 12 | Baseline, 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). |
| Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment | Baseline, 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. |
Countries
Belgium, Canada, Czechia, Germany, Hungary, Poland, United States
Participant flow
Recruitment details
A total of 71 sites were authorized to recruit subjects for the trial between July 2017 and July 2019. The trial sites that screened subjects to the trial were: 5 in Belgium, 10 in Canada, 5 in Czech Republic, 2 in Germany, 5 in Hungary, 1 in Poland and 43 in the Unites States of America (USA).
Pre-assignment details
A total of 1721 subjects were screened, wherein, 531 met the eligibility criteria and entered the enrichment period. Of these, 302 subjects met the eligibility criteria at Visit (V) 4 (randomization), and were randomized to treatment with FE 201836 (different doses), placebo, or desmopressin. A total of 278 subjects completed the trial.
Participants by arm
| Arm | Count |
|---|---|
| FE 201836 500 µg (Randomized Treatment Period) FE 201836 500 µg oral solution and placebo ODT, administered once daily | 60 |
| FE 201836 350 µg (Randomized Treatment Period) FE 201836 350 µg oral solution and placebo ODT, administered once daily | 27 |
| FE 201836 250 µg (Randomized Treatment Period) FE 201836 250 µg oral solution and placebo ODT, administered once daily | 24 |
| FE 201836 150 µg (Randomized Treatment Period) FE 201836 150 µg oral solution and placebo ODT, administered once daily | 14 |
| FE 201836 100 µg (Randomized Treatment Period) FE 201836 100 µg oral solution and placebo ODT, administered once daily | 13 |
| FE 201836 50 µg (Randomized Treatment Period) FE 201836 50 µg oral solution and placebo ODT, administered once daily | 34 |
| Placebo (Randomized Treatment Period) Placebo oral solution and placebo ODT, administered once daily | 87 |
| Desmopressin 25µg (Randomized Treatment Period) Desmopressin 25 µg ODT and placebo oral solution, administered once daily (female subjects) | 26 |
| Desmopressin 50 µg (Randomized Treatment Period) Desmopressin 50 µg ODT and placebo oral solution, administered once daily (male subjects) | 17 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 0 | 0 | 1 | 1 | 5 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Deviation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 2 | 1 | 0 | 0 | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | FE 201836 350 µg (Randomized Treatment Period) | FE 201836 250 µg (Randomized Treatment Period) | FE 201836 150 µg (Randomized Treatment Period) | FE 201836 100 µg (Randomized Treatment Period) | FE 201836 50 µg (Randomized Treatment Period) | FE 201836 500 µg (Randomized Treatment Period) | Placebo (Randomized Treatment Period) | Desmopressin 25µg (Randomized Treatment Period) | Desmopressin 50 µg (Randomized Treatment Period) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.0 years STANDARD_DEVIATION 14.3 | 60.8 years STANDARD_DEVIATION 13 | 63.9 years STANDARD_DEVIATION 7.5 | 61.5 years STANDARD_DEVIATION 9.2 | 59.1 years STANDARD_DEVIATION 10.4 | 59.0 years STANDARD_DEVIATION 14.1 | 58.9 years STANDARD_DEVIATION 13.9 | 51.1 years STANDARD_DEVIATION 11.1 | 60.9 years STANDARD_DEVIATION 9.5 | 58.8 years STANDARD_DEVIATION 12.8 |
| Age, Customized <65 years old | 19 years | 14 years | 6 years | 6 years | 21 years | 35 years | 52 years | 24 years | 11 years | 188 years |
| Age, Customized >=65 years old | 8 years | 10 years | 8 years | 7 years | 13 years | 25 years | 35 years | 2 years | 6 years | 114 years |
| Baseline body mass index (BMI) | 29.91 kg/m^2 STANDARD_DEVIATION 4.64 | 29.56 kg/m^2 STANDARD_DEVIATION 6.5 | 32.03 kg/m^2 STANDARD_DEVIATION 8.26 | 31.52 kg/m^2 STANDARD_DEVIATION 4.6 | 30.93 kg/m^2 STANDARD_DEVIATION 6.16 | 30.66 kg/m^2 STANDARD_DEVIATION 6.05 | 29.54 kg/m^2 STANDARD_DEVIATION 5.14 | 31.89 kg/m^2 STANDARD_DEVIATION 7.99 | 31.05 kg/m^2 STANDARD_DEVIATION 6.49 | 30.44 kg/m^2 STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 6 Participants | 3 Participants | 7 Participants | 12 Participants | 17 Participants | 35 Participants | 12 Participants | 4 Participants | 105 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 18 Participants | 11 Participants | 6 Participants | 22 Participants | 42 Participants | 51 Participants | 14 Participants | 13 Participants | 195 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Insomnia Severity Index (ISI) | 15.7 score on a scale STANDARD_DEVIATION 6.1 | 14.3 score on a scale STANDARD_DEVIATION 5.1 | 13.0 score on a scale STANDARD_DEVIATION 6.7 | 16.4 score on a scale STANDARD_DEVIATION 5.6 | 14.7 score on a scale STANDARD_DEVIATION 4.8 | 15.8 score on a scale STANDARD_DEVIATION 5.4 | 15.6 score on a scale STANDARD_DEVIATION 5.8 | 18.2 score on a scale STANDARD_DEVIATION 4.7 | 15.5 score on a scale STANDARD_DEVIATION 6.8 | 15.6 score on a scale STANDARD_DEVIATION 5.6 |
| Mean NI Diary Overall Impact Score | 62.3 score on a scale STANDARD_DEVIATION 29.8 | 55.9 score on a scale STANDARD_DEVIATION 21.6 | 53.0 score on a scale STANDARD_DEVIATION 30.6 | 68.6 score on a scale STANDARD_DEVIATION 20.7 | 59.9 score on a scale STANDARD_DEVIATION 26.8 | 59.2 score on a scale STANDARD_DEVIATION 25.4 | 62.7 score on a scale STANDARD_DEVIATION 26.8 | 71.5 score on a scale STANDARD_DEVIATION 23.8 | 54.2 score on a scale STANDARD_DEVIATION 28 | 61.2 score on a scale STANDARD_DEVIATION 26.3 |
| Mean Nocturia Impact (NI) Diary Total Score | 47.03 score on a scale STANDARD_DEVIATION 28.44 | 38.76 score on a scale STANDARD_DEVIATION 19.09 | 36.28 score on a scale STANDARD_DEVIATION 22.1 | 51.63 score on a scale STANDARD_DEVIATION 17.73 | 42.46 score on a scale STANDARD_DEVIATION 23.28 | 47.20 score on a scale STANDARD_DEVIATION 18.39 | 47.66 score on a scale STANDARD_DEVIATION 21.25 | 58.06 score on a scale STANDARD_DEVIATION 20.78 | 39.88 score on a scale STANDARD_DEVIATION 23.08 | 46.30 score on a scale STANDARD_DEVIATION 21.81 |
| Mean Nocturnal Polyuria Index | 46.76 percentage STANDARD_DEVIATION 10.08 | 49.75 percentage STANDARD_DEVIATION 15.96 | 50.99 percentage STANDARD_DEVIATION 12.93 | 44.59 percentage STANDARD_DEVIATION 6.58 | 47.01 percentage STANDARD_DEVIATION 9.86 | 48.87 percentage STANDARD_DEVIATION 12.04 | 47.91 percentage STANDARD_DEVIATION 14.29 | 49.21 percentage STANDARD_DEVIATION 13.93 | 49.10 percentage STANDARD_DEVIATION 17.93 | 48.24 percentage STANDARD_DEVIATION 12.99 |
| Mean Nocturnal Urine Volume (NUV) | 766.0 mL STANDARD_DEVIATION 242.1 | 897.3 mL STANDARD_DEVIATION 373.6 | 803.1 mL STANDARD_DEVIATION 304.7 | 892.4 mL STANDARD_DEVIATION 206.7 | 879.9 mL STANDARD_DEVIATION 354.1 | 804.6 mL STANDARD_DEVIATION 313.8 | 752.3 mL STANDARD_DEVIATION 269.5 | 839.3 mL STANDARD_DEVIATION 286.4 | 803.5 mL STANDARD_DEVIATION 425.8 | 808.8 mL STANDARD_DEVIATION 307.5 |
| Mean Number of Nocturnal Voids | 3.01 nocturnal voids STANDARD_DEVIATION 0.72 | 3.10 nocturnal voids STANDARD_DEVIATION 1.11 | 2.98 nocturnal voids STANDARD_DEVIATION 0.84 | 3.33 nocturnal voids STANDARD_DEVIATION 0.82 | 3.24 nocturnal voids STANDARD_DEVIATION 1.18 | 2.88 nocturnal voids STANDARD_DEVIATION 0.84 | 3.09 nocturnal voids STANDARD_DEVIATION 0.83 | 3.38 nocturnal voids STANDARD_DEVIATION 1.45 | 3.16 nocturnal voids STANDARD_DEVIATION 1.22 | 3.09 nocturnal voids STANDARD_DEVIATION 0.98 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 6 Participants | 5 Participants | 6 Participants | 4 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 22 Participants | 14 Participants | 11 Participants | 31 Participants | 52 Participants | 78 Participants | 19 Participants | 13 Participants | 264 Participants |
| Sex: Female, Male Female | 18 Participants | 16 Participants | 5 Participants | 8 Participants | 16 Participants | 40 Participants | 51 Participants | 26 Participants | 0 Participants | 180 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 9 Participants | 5 Participants | 18 Participants | 20 Participants | 36 Participants | 0 Participants | 17 Participants | 122 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 531 | 0 / 60 | 0 / 27 | 0 / 24 | 0 / 14 | 0 / 13 | 0 / 34 | 0 / 87 | 0 / 26 | 0 / 17 |
| other Total, other adverse events | 0 / 531 | 16 / 60 | 3 / 27 | 3 / 24 | 8 / 14 | 5 / 13 | 7 / 34 | 16 / 87 | 8 / 26 | 9 / 17 |
| serious Total, serious adverse events | 2 / 531 | 1 / 60 | 2 / 27 | 1 / 24 | 0 / 14 | 1 / 13 | 0 / 34 | 2 / 87 | 0 / 26 | 0 / 17 |
Outcome results
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.
Time frame: Baseline, during 12 weeks of treatment
Population: The intention-to-treat analysis set for the randomized treatment period (ITT-RT) comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment | -1.06 nocturnal voids |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment | -0.99 nocturnal voids |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment | -0.89 nocturnal voids |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment | -0.80 nocturnal voids |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment | -0.77 nocturnal voids |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment | -0.76 nocturnal voids |
| Placebo (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment | -0.76 nocturnal voids |
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.54, -0.07]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.46, -0.02]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.36, 0]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.23, 0]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.14, 0]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.07, 0]
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.
Time frame: Baseline, During 12 Weeks of Treatment
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment | 154.98 minutes |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment | 150.23 minutes |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment | 145.95 minutes |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment | 140.74 minutes |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment | 139.19 minutes |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment | 138.13 minutes |
| Placebo (Randomized Treatment Period) | Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment | 137.45 minutes |
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-6.19, 62.09]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.73, 55.89]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.14, 47.28]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.01, 28.07]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [0, 17.9]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [0, 7.55]
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.
Time frame: Baseline, during 12 weeks of treatment
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment | -6.50 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment | -6.25 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment | -6.11 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment | -6.00 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment | -5.98 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment | -5.97 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment | -5.96 score on a scale |
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-6.09, 2.28]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-4.3, 0.75]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-2.44, 0.33]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.92, 0.07]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.48, 0.02]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.15, 0]
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.
Time frame: Baseline, during 12 weeks of treatment
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment | -12.40 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment | -12.69 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment | -12.75 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment | -12.77 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment | -12.77 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment | -12.78 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment | -12.77 score on a scale |
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-1.41, 5.47]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.43, 1.19]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.16, 0.5]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.03, 0.15]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [-0.01, 0.05]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [0, 0.01]
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.
Time frame: Baseline, Week 1
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1 | -0.649 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1 | -1.072 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1 | -0.748 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1 | -0.458 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1 | -0.346 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1 | -0.376 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1 | -0.570 score on a scale |
p-value: 0.638195% CI: [-0.409, 0.251]MMRM
p-value: 0.022195% CI: [-0.931, -0.073]MMRM
p-value: 0.411295% CI: [-0.602, 0.247]MMRM
p-value: 0.676195% CI: [-0.416, 0.64]MMRM
p-value: 0.489895% CI: [-0.414, 0.861]MMRM
p-value: 0.331195% CI: [-0.198, 0.585]MMRM
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.
Time frame: Baseline, Week 12
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12 | -0.992 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12 | -1.249 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12 | -0.700 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12 | -0.880 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12 | -0.974 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12 | -0.921 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12 | -0.769 score on a scale |
p-value: 0.241295% CI: [-0.598, 0.151]MMRM
p-value: 0.050195% CI: [-0.959, 0]MMRM
p-value: 0.778895% CI: [-0.417, 0.556]MMRM
p-value: 0.711195% CI: [-0.698, 0.477]MMRM
p-value: 0.581695% CI: [-0.937, 0.527]MMRM
p-value: 0.498195% CI: [-0.595, 0.29]MMRM
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.
Time frame: Baseline, Week 4
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4 | -0.896 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4 | -0.940 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4 | -0.712 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4 | -0.606 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4 | -1.096 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4 | -0.861 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4 | -0.665 score on a scale |
p-value: 0.825695% CI: [-0.463, 0.369]MMRM
p-value: 0.158395% CI: [-0.551, 0.09]MMRM
p-value: 0.188495% CI: [-0.685, 0.136]MMRM
p-value: 0.819895% CI: [-0.455, 0.574]MMRM
p-value: 0.179395% CI: [-1.061, 0.199]MMRM
p-value: 0.315595% CI: [-0.581, 0.189]MMRM
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.
Time frame: Baseline, Week 8
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8 | -0.972 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8 | -1.044 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8 | -0.991 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8 | -0.499 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8 | -1.012 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8 | -0.881 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8 | -0.731 score on a scale |
p-value: 0.18395% CI: [-0.596, 0.114]MMRM
p-value: 0.161895% CI: [-0.751, 0.126]MMRM
p-value: 0.251995% CI: [-0.706, 0.186]MMRM
p-value: 0.404495% CI: [-0.316, 0.781]MMRM
p-value: 0.434895% CI: [-0.986, 0.426]MMRM
p-value: 0.478695% CI: [-0.565, 0.266]MMRM
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.
Time frame: Baseline, Week 12
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 12 | -7.807 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 12 | -9.329 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 12 | -6.355 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 12 | -6.193 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 12 | -5.002 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 12 | -7.908 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in ISI at Week 12 | -6.678 score on a scale |
p-value: 0.289695% CI: [-3.226, 0.967]MMRM
p-value: 0.049895% CI: [-5.301, -0.003]MMRM
p-value: 0.815995% CI: [-2.409, 3.055]MMRM
p-value: 0.771995% CI: [-2.809, 3.779]MMRM
p-value: 0.419395% CI: [-2.407, 5.76]MMRM
p-value: 0.333395% CI: [-3.73, 1.27]MMRM
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.
Time frame: Baseline, Week 4
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 4 | -6.589 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 4 | -6.652 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 4 | -5.630 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 4 | -5.428 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 4 | -4.510 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 4 | -6.372 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in ISI at Week 4 | -5.277 score on a scale |
p-value: 0.173395% CI: [-3.207, 0.582]MMRM
p-value: 0.253895% CI: [-3.745, 0.994]MMRM
p-value: 0.778295% CI: [-2.818, 2.113]MMRM
p-value: 0.921895% CI: [-3.182, 2.88]MMRM
p-value: 0.682395% CI: [-2.923, 4.457]MMRM
p-value: 0.343695% CI: [-3.369, 1.179]MMRM
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.
Time frame: Baseline, Week 8
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 8 | -7.643 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 8 | -8.091 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 8 | -6.693 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 8 | -6.959 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 8 | -5.707 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in ISI at Week 8 | -7.167 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in ISI at Week 8 | -6.408 score on a scale |
p-value: 0.204295% CI: [-3.146, 0.676]MMRM
p-value: 0.159195% CI: [-4.031, 0.665]MMRM
p-value: 0.816895% CI: [-2.708, 2.138]MMRM
p-value: 0.714895% CI: [-3.517, 2.416]MMRM
p-value: 0.714195% CI: [-3.066, 4.468]MMRM
p-value: 0.504195% CI: [-2.995, 1.477]MMRM
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).
Time frame: Baseline, Week 1
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1 | 122.9 minutes |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1 | 187.0 minutes |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1 | 106.0 minutes |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1 | 91.7 minutes |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1 | 82.9 minutes |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1 | 51.3 minutes |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1 | 81.1 minutes |
p-value: 0.00195% CI: [43.4, 168.4]MMRM
p-value: 0.441895% CI: [-38.8, 88.6]MMRM
p-value: 0.790295% CI: [-68.2, 89.6]MMRM
p-value: 0.085395% CI: [-5.9, 89.6]MMRM
p-value: 0.966495% CI: [-84.2, 87.9]MMRM
p-value: 0.297795% CI: [-85.9, 26.4]MMRM
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).
Time frame: Baseline, Week 12
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 12 | 178.5 minutes |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 12 | 160.0 minutes |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 12 | 180.7 minutes |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 12 | 111.5 minutes |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 12 | 141.1 minutes |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 12 | 166.2 minutes |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 12 | 162.8 minutes |
p-value: 0.596495% CI: [-42.7, 74.2]MMRM
p-value: 0.941895% CI: [-78.5, 72.9]MMRM
p-value: 0.645295% CI: [-58.8, 94.7]MMRM
p-value: 0.256595% CI: [-140.2, 37.6]MMRM
p-value: 0.660595% CI: [-118.6, 75.4]MMRM
p-value: 0.919195% CI: [-62.6, 69.4]MMRM
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).
Time frame: Baseline, Week 4
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 4 | 164.5 minutes |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 4 | 211.0 minutes |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 4 | 132.3 minutes |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 4 | 89.5 minutes |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 4 | 122.0 minutes |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 4 | 95.5 minutes |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 4 | 150.2 minutes |
p-value: 0.552395% CI: [-33, 61.5]MMRM
p-value: 0.055695% CI: [-1.5, 123]MMRM
p-value: 0.583795% CI: [-82, 46.3]MMRM
p-value: 0.136395% CI: [-140.7, 19.3]MMRM
p-value: 0.493895% CI: [-109.1, 52.8]MMRM
p-value: 0.053595% CI: [-110.2, 0.8]MMRM
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).
Time frame: Baseline, Week 8
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 8 | 160.4 minutes |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 8 | 225.4 minutes |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 8 | 190.2 minutes |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 8 | 136.8 minutes |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 8 | 163.2 minutes |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 8 | 164.3 minutes |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean Duration of FUSP at Week 8 | 161.0 minutes |
p-value: 0.982995% CI: [-62.2, 60.9]MMRM
p-value: 0.103895% CI: [-13.3, 142.1]MMRM
p-value: 0.476495% CI: [-51.4, 109.8]MMRM
p-value: 0.620495% CI: [-120.5, 72]MMRM
p-value: 0.96695% CI: [-100.1, 104.6]MMRM
p-value: 0.927595% CI: [-67.4, 73.9]MMRM
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.
Time frame: Baseline, Week 1
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 1 | -10.98 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 1 | -30.39 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 1 | -15.51 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 1 | -11.77 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 1 | -2.79 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 1 | -12.26 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 1 | -13.46 score on a scale |
p-value: 0.484695% CI: [-4.5, 9.46]MMRM
p-value: 0.000495% CI: [-26.26, -7.6]MMRM
p-value: 0.668595% CI: [-11.47, 7.37]MMRM
p-value: 0.777295% CI: [-10.07, 13.46]MMRM
p-value: 0.089595% CI: [-1.66, 23]MMRM
p-value: 0.78295% CI: [-7.34, 9.74]MMRM
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.
Time frame: Baseline, Week 12
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 12 | -30.47 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 12 | -36.76 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 12 | -20.84 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 12 | -15.32 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 12 | -28.89 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 12 | -27.13 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 12 | -30.03 score on a scale |
p-value: 0.924595% CI: [-9.43, 8.57]MMRM
p-value: 0.265795% CI: [-18.59, 5.15]MMRM
p-value: 0.138395% CI: [-2.99, 21.38]MMRM
p-value: 0.052395% CI: [-0.15, 29.59]MMRM
p-value: 0.885595% CI: [-14.47, 16.75]MMRM
p-value: 0.597295% CI: [-7.91, 13.72]MMRM
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.
Time frame: Baseline, Week 4
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 4 | -22.17 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 4 | -26.07 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 4 | -19.35 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 4 | -18.36 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 4 | -17.95 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 4 | -21.40 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 4 | -21.75 score on a scale |
p-value: 0.917595% CI: [-8.25, 7.42]MMRM
p-value: 0.409895% CI: [-14.62, 5.98]MMRM
p-value: 0.656695% CI: [-8.25, 13.06]MMRM
p-value: 0.614495% CI: [-9.85, 16.63]MMRM
p-value: 0.579895% CI: [-9.71, 17.31]MMRM
p-value: 0.941795% CI: [-9.17, 9.88]MMRM
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.
Time frame: Baseline, Week 8
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 8 | -28.13 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 8 | -34.97 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 8 | -21.71 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 8 | -19.03 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 8 | -23.84 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 8 | -20.70 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Overall Impact Score at Week 8 | -25.32 score on a scale |
p-value: 0.514895% CI: [-11.31, 5.68]MMRM
p-value: 0.087995% CI: [-20.75, 1.44]MMRM
p-value: 0.533595% CI: [-7.79, 15]MMRM
p-value: 0.378795% CI: [-7.76, 20.34]MMRM
p-value: 0.844895% CI: [-13.41, 16.38]MMRM
p-value: 0.375195% CI: [-5.63, 14.87]MMRM
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.
Time frame: Baseline, Week 1
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 1 | -7.55 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 1 | -21.91 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 1 | -10.90 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 1 | -8.93 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 1 | -9.68 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 1 | -8.75 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 1 | -8.07 score on a scale |
p-value: 0.846395% CI: [-4.75, 5.78]MMRM
p-value: 0.000195% CI: [-20.89, -6.81]MMRM
p-value: 0.435595% CI: [-9.99, 4.32]MMRM
p-value: 0.848395% CI: [-9.79, 8.06]MMRM
p-value: 0.733695% CI: [-10.91, 7.69]MMRM
p-value: 0.834795% CI: [-7.15, 5.78]MMRM
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.
Time frame: Baseline, Week 12
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 12 | -16.92 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 12 | -24.44 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 12 | -14.68 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 12 | -10.13 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 12 | -22.59 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 12 | -17.18 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 12 | -17.45 score on a scale |
p-value: 0.864695% CI: [-5.54, 6.59]MMRM
p-value: 0.08795% CI: [-15, 1.02]MMRM
p-value: 0.5195% CI: [-5.5, 11.04]MMRM
p-value: 0.153595% CI: [-2.75, 17.39]MMRM
p-value: 0.336995% CI: [-15.66, 5.38]MMRM
p-value: 0.941795% CI: [-7.05, 7.59]MMRM
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.
Time frame: Baseline, Week 4
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 4 | -12.62 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 4 | -17.44 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 4 | -14.37 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 4 | -11.23 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 4 | -22.23 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 4 | -13.29 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 4 | -14.20 score on a scale |
p-value: 0.569595% CI: [-3.9, 7.07]MMRM
p-value: 0.378495% CI: [-10.46, 3.99]MMRM
p-value: 0.965395% CI: [-7.67, 7.34]MMRM
p-value: 0.530495% CI: [-6.35, 12.29]MMRM
p-value: 0.096895% CI: [-17.51, 1.46]MMRM
p-value: 0.788595% CI: [-5.79, 7.62]MMRM
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.
Time frame: Baseline, Week 8
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 8 | -16.03 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 8 | -23.22 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 8 | -15.10 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 8 | -12.04 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 8 | -19.23 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 8 | -14.11 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean NI Diary Total Score at Week 8 | -14.83 score on a scale |
p-value: 0.679295% CI: [-6.89, 4.5]MMRM
p-value: 0.027695% CI: [-15.84, -0.93]MMRM
p-value: 0.944595% CI: [-7.97, 7.42]MMRM
p-value: 0.563795% CI: [-6.71, 12.28]MMRM
p-value: 0.38795% CI: [-14.39, 5.6]MMRM
p-value: 0.837395% CI: [-6.19, 7.63]MMRM
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).
Time frame: Baseline, Week 1
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 1 | -0.714 nocturnal voids |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 1 | -1.162 nocturnal voids |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 1 | -0.722 nocturnal voids |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 1 | -0.520 nocturnal voids |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 1 | -0.722 nocturnal voids |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 1 | -0.325 nocturnal voids |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 1 | -0.575 nocturnal voids |
p-value: 0.421495% CI: [-0.48, 0.201]MMRM
p-value: 0.010195% CI: [-1.034, -0.141]MMRM
p-value: 0.520395% CI: [-0.599, 0.304]MMRM
p-value: 0.848395% CI: [-0.508, 0.617]MMRM
p-value: 0.635795% CI: [-0.759, 0.464]MMRM
p-value: 0.222295% CI: [-0.152, 0.652]MMRM
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.
Time frame: Baseline, Week 12
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 12 | -1.256 nocturnal voids |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 12 | -1.120 nocturnal voids |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 12 | -0.850 nocturnal voids |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 12 | -0.674 nocturnal voids |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 12 | -1.053 nocturnal voids |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 12 | -0.921 nocturnal voids |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 12 | -0.957 nocturnal voids |
p-value: 0.110695% CI: [-0.667, 0.069]MMRM
p-value: 0.500595% CI: [-0.639, 0.313]MMRM
p-value: 0.660495% CI: [-0.372, 0.586]MMRM
p-value: 0.317895% CI: [-0.275, 0.842]MMRM
p-value: 0.756195% CI: [-0.701, 0.51]MMRM
p-value: 0.861495% CI: [-0.378, 0.452]MMRM
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.
Time frame: Baseline, Week 4
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -1.078 nocturnal voids |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -1.330 nocturnal voids |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -0.784 nocturnal voids |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -0.471 nocturnal voids |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -0.952 nocturnal voids |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -0.518 nocturnal voids |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 4 | -0.912 nocturnal voids |
p-value: 0.882695% CI: [-0.568, 0.488]MMRM
p-value: 0.04495% CI: [-0.824, -0.011]MMRM
p-value: 0.543895% CI: [-0.288, 0.545]MMRM
p-value: 0.09695% CI: [-0.079, 0.962]MMRM
p-value: 0.290995% CI: [-0.474, 0.143]MMRM
p-value: 0.034495% CI: [0.029, 0.759]MMRM
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.
Time frame: Baseline, Week 8
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 8 | -1.085 nocturnal voids |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 8 | -1.177 nocturnal voids |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 8 | -0.965 nocturnal voids |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 8 | -0.490 nocturnal voids |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 8 | -1.077 nocturnal voids |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 8 | -0.786 nocturnal voids |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean Number of Nocturnal Voids at Week 8 | -0.953 nocturnal voids |
p-value: 0.473295% CI: [-0.496, 0.231]MMRM
p-value: 0.339495% CI: [-0.685, 0.237]MMRM
p-value: 0.9695% CI: [-0.488, 0.463]MMRM
p-value: 0.113195% CI: [-0.111, 1.037]MMRM
p-value: 0.685395% CI: [-0.729, 0.48]MMRM
p-value: 0.436495% CI: [-0.254, 0.587]MMRM
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).
Time frame: Baseline, Week 12
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV at Week 12 | -367.3 mL |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV at Week 12 | -392.4 mL |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV at Week 12 | -411.3 mL |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV at Week 12 | -284.2 mL |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV at Week 12 | -393.5 mL |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV at Week 12 | -403.2 mL |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean NUV at Week 12 | -317.8 mL |
p-value: 0.327395% CI: [-148.9, 49.9]MMRM
p-value: 0.2595% CI: [-202, 52.9]MMRM
p-value: 0.153795% CI: [-222.3, 35.2]MMRM
p-value: 0.651595% CI: [-113.1, 180.3]MMRM
p-value: 0.350695% CI: [-235.3, 83.9]MMRM
p-value: 0.125595% CI: [-194.8, 24.1]MMRM
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).
Time frame: Baseline, Week 1
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV in Week 1 | -328.8 mL |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV in Week 1 | -371.8 mL |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV in Week 1 | -352.4 mL |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV in Week 1 | -265.5 mL |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV in Week 1 | -312.6 mL |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Mean NUV in Week 1 | -218.2 mL |
| Placebo (Randomized Treatment Period) | Change From Baseline in Mean NUV in Week 1 | -241.6 mL |
p-value: 0.04795% CI: [-173.2, -1.2]MMRM
p-value: 0.023795% CI: [-242.9, -17.6]MMRM
p-value: 0.056995% CI: [-224.9, 3.3]MMRM
p-value: 0.738395% CI: [-164.8, 117]MMRM
p-value: 0.362695% CI: [-224.3, 82.3]MMRM
p-value: 0.652495% CI: [-78.9, 125.7]MMRM
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.
Time frame: Baseline, Week 1
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1 | -0.575 mL/min |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1 | -0.635 mL/min |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1 | -0.610 mL/min |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1 | -0.459 mL/min |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1 | -0.523 mL/min |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1 | -0.328 mL/min |
| Placebo (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1 | -0.402 mL/min |
p-value: 0.019695% CI: [-0.318, -0.028]MMRM
p-value: 0.016795% CI: [-0.423, -0.043]MMRM
p-value: 0.035295% CI: [-0.401, -0.015]MMRM
p-value: 0.640295% CI: [-0.295, 0.182]MMRM
p-value: 0.360295% CI: [-0.381, 0.139]MMRM
p-value: 0.401895% CI: [-0.099, 0.247]MMRM
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.
Time frame: Baseline, Week 12
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12 | -0.648 mL/min |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12 | -0.606 mL/min |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12 | -0.735 mL/min |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12 | -0.458 mL/min |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12 | -0.685 mL/min |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12 | -0.651 mL/min |
| Placebo (Randomized Treatment Period) | Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12 | -0.515 mL/min |
p-value: 0.135495% CI: [-0.308, 0.042]MMRM
p-value: 0.423895% CI: [-0.315, 0.133]MMRM
p-value: 0.057495% CI: [-0.446, 0.007]MMRM
p-value: 0.657995% CI: [-0.199, 0.315]MMRM
p-value: 0.233795% CI: [-0.45, 0.11]MMRM
p-value: 0.163995% CI: [-0.328, 0.056]MMRM
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.
Time frame: Baseline, Week 1
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1 | -0.739 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1 | -0.970 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1 | -0.811 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1 | -0.643 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1 | -0.417 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1 | -0.719 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1 | -0.593 score on a scale |
p-value: 0.23595% CI: [-0.388, 0.096]MMRM
p-value: 0.021595% CI: [-0.699, -0.056]MMRM
p-value: 0.181895% CI: [-0.54, 0.103]MMRM
p-value: 0.806395% CI: [-0.45, 0.35]MMRM
p-value: 0.441495% CI: [-0.274, 0.627]MMRM
p-value: 0.417995% CI: [-0.432, 0.18]MMRM
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.
Time frame: Baseline, Week 12
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 12 | -1.181 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 12 | -1.338 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 12 | -0.894 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 12 | -0.638 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 12 | -1.168 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 12 | -1.041 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 12 | -0.853 score on a scale |
p-value: 0.013395% CI: [-0.587, -0.069]MMRM
p-value: 0.004895% CI: [-0.819, -0.15]MMRM
p-value: 0.822395% CI: [-0.395, 0.314]MMRM
p-value: 0.308395% CI: [-0.2, 0.63]MMRM
p-value: 0.155695% CI: [-0.75, 0.121]MMRM
p-value: 0.242395% CI: [-0.504, 0.128]MMRM
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.
Time frame: Baseline, Week 4
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 4 | -0.837 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 4 | -1.025 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 4 | -0.798 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 4 | -0.749 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 4 | -0.656 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 4 | -0.936 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 4 | -0.898 score on a scale |
p-value: 0.604295% CI: [-0.17, 0.292]MMRM
p-value: 0.411495% CI: [-0.432, 0.177]MMRM
p-value: 0.539495% CI: [-0.219, 0.418]MMRM
p-value: 0.45995% CI: [-0.246, 0.544]MMRM
p-value: 0.239795% CI: [-0.163, 0.647]MMRM
p-value: 0.795495% CI: [-0.332, 0.254]MMRM
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.
Time frame: Baseline, Week 8
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 8 | -1.132 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 8 | -1.410 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 8 | -0.825 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 8 | -0.643 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 8 | -0.816 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 8 | -1.013 score on a scale |
| Placebo (Randomized Treatment Period) | Change From Baseline in PGI-S Scores at Week 8 | -0.800 score on a scale |
p-value: 0.007795% CI: [-0.576, -0.089]MMRM
p-value: 0.000295% CI: [-0.927, -0.293]MMRM
p-value: 0.877895% CI: [-0.352, 0.301]MMRM
p-value: 0.430995% CI: [-0.235, 0.549]MMRM
p-value: 0.939295% CI: [-0.444, 0.411]MMRM
p-value: 0.173495% CI: [-0.521, 0.094]MMRM
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.
Time frame: Week 1
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1 | 2.475 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1 | 2.045 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1 | 2.708 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1 | 2.786 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1 | 2.781 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1 | 2.758 score on a scale |
| Placebo (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1 | 2.745 score on a scale |
p-value: 0.05595% CI: [-0.545, 0.006]MMRM
p-value: 0.000295% CI: [-1.066, -0.335]MMRM
p-value: 0.84495% CI: [-0.404, 0.33]MMRM
p-value: 0.86195% CI: [-0.417, 0.498]MMRM
p-value: 0.887195% CI: [-0.46, 0.532]MMRM
p-value: 0.939695% CI: [-0.313, 0.338]MMRM
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.
Time frame: Week 12
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12 | 1.667 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12 | 1.671 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12 | 2.656 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12 | 2.452 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12 | 1.678 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12 | 2.384 score on a scale |
| Placebo (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12 | 2.490 score on a scale |
p-value: <0.000195% CI: [-1.22, -0.424]MMRM
p-value: 0.001995% CI: [-1.331, -0.306]MMRM
p-value: 0.55195% CI: [-0.383, 0.716]MMRM
p-value: 0.908695% CI: [-0.685, 0.61]MMRM
p-value: 0.018595% CI: [-1.486, -0.138]MMRM
p-value: 0.653795% CI: [-0.569, 0.357]MMRM
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.
Time frame: Week 4
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4 | 2.121 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4 | 2.191 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4 | 2.447 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4 | 2.521 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4 | 2.385 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4 | 2.582 score on a scale |
| Placebo (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4 | 2.596 score on a scale |
p-value: 0.00595% CI: [-0.806, -0.145]MMRM
p-value: 0.066595% CI: [-0.837, 0.028]MMRM
p-value: 0.524595% CI: [-0.608, 0.31]MMRM
p-value: 0.794795% CI: [-0.642, 0.492]MMRM
p-value: 0.462595% CI: [-0.777, 0.355]MMRM
p-value: 0.946595% CI: [-0.412, 0.385]MMRM
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.
Time frame: Week 8
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8 | 1.843 score on a scale |
| FE 201836 350 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8 | 1.887 score on a scale |
| FE 201836 250 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8 | 2.528 score on a scale |
| FE 201836 150 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8 | 2.286 score on a scale |
| FE 201836 100 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8 | 2.155 score on a scale |
| FE 201836 50 ug (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8 | 2.273 score on a scale |
| Placebo (Randomized Treatment Period) | Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8 | 2.573 score on a scale |
p-value: <0.000195% CI: [-1.078, -0.383]MMRM
p-value: 0.00395% CI: [-1.137, -0.236]MMRM
p-value: 0.85295% CI: [-0.517, 0.427]MMRM
p-value: 0.320595% CI: [-0.856, 0.281]MMRM
p-value: 0.176995% CI: [-1.026, 0.19]MMRM
p-value: 0.158495% CI: [-0.717, 0.118]MMRM
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.
Time frame: During 12 weeks of treatment
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment | 67.2 percentage of nights |
| FE 201836 350 ug (Randomized Treatment Period) | Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment | 77.5 percentage of nights |
| FE 201836 250 ug (Randomized Treatment Period) | Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment | 64.5 percentage of nights |
| FE 201836 150 ug (Randomized Treatment Period) | Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment | 55.3 percentage of nights |
| FE 201836 100 ug (Randomized Treatment Period) | Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment | 73.2 percentage of nights |
| FE 201836 50 ug (Randomized Treatment Period) | Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment | 61.4 percentage of nights |
| Placebo (Randomized Treatment Period) | Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment | 62.0 percentage of nights |
p-value: 0.332895% CI: [-5.3, 15.7]ANCOVA
p-value: 0.025595% CI: [1.9, 29.2]ANCOVA
p-value: 0.729695% CI: [-11.7, 16.7]ANCOVA
p-value: 0.458695% CI: [-24.5, 11.1]ANCOVA
p-value: 0.232795% CI: [-7.2, 29.5]ANCOVA
p-value: 0.92495% CI: [-13.3, 12.1]ANCOVA
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.
Time frame: During 12 weeks of treatment
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment | 23.3 percentage of nights |
| FE 201836 350 ug (Randomized Treatment Period) | Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment | 28.8 percentage of nights |
| FE 201836 250 ug (Randomized Treatment Period) | Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment | 17.3 percentage of nights |
| FE 201836 150 ug (Randomized Treatment Period) | Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment | 12.9 percentage of nights |
| FE 201836 100 ug (Randomized Treatment Period) | Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment | 14.8 percentage of nights |
| FE 201836 50 ug (Randomized Treatment Period) | Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment | 21.5 percentage of nights |
| Placebo (Randomized Treatment Period) | Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment | 23.0 percentage of nights |
p-value: 0.949995% CI: [-7.9, 8.5]ANCOVA
p-value: 0.284295% CI: [-4.8, 16.4]ANCOVA
p-value: 0.3195% CI: [-16.8, 5.4]ANCOVA
p-value: 0.149995% CI: [-23.9, 3.7]ANCOVA
p-value: 0.257195% CI: [-22.5, 6]ANCOVA
p-value: 0.762995% CI: [-11.4, 8.3]ANCOVA
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%).
Time frame: Week 1
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 1 | 0.844 odd of response |
| FE 201836 350 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 1 | 1.202 odd of response |
| FE 201836 250 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 1 | 0.682 odd of response |
| FE 201836 150 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 1 | 0.818 odd of response |
| FE 201836 100 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 1 | 0.810 odd of response |
| FE 201836 50 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 1 | 0.513 odd of response |
| Placebo (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 1 | 0.480 odd of response |
p-value: 0.11795% CI: [0.869, 3.56]Regression, Logistic
p-value: 0.04895% CI: [1.01, 6.214]Regression, Logistic
p-value: 0.4695% CI: [0.56, 3.602]Regression, Logistic
p-value: 0.36795% CI: [0.535, 5.427]Regression, Logistic
p-value: 0.40795% CI: [0.489, 5.825]Regression, Logistic
p-value: 0.87695% CI: [0.462, 2.473]Regression, Logistic
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%).
Time frame: Week 12
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 12 | 3.914 odd of response |
| FE 201836 350 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 12 | 1.891 odd of response |
| FE 201836 250 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 12 | 1.824 odd of response |
| FE 201836 150 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 12 | 0.854 odd of response |
| FE 201836 100 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 12 | 1.400 odd of response |
| FE 201836 50 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 12 | 1.395 odd of response |
| Placebo (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 12 | 1.590 odd of response |
p-value: 0.04695% CI: [1.017, 5.961]Regression, Logistic
p-value: 0.74595% CI: [0.418, 3.386]Regression, Logistic
p-value: 0.7995% CI: [0.417, 3.155]Regression, Logistic
p-value: 0.29395% CI: [0.169, 1.71]Regression, Logistic
p-value: 0.84395% CI: [0.252, 3.076]Regression, Logistic
p-value: 0.76395% CI: [0.375, 2.053]Regression, Logistic
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%).
Time frame: Week 4
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 4 | 1.199 odd of response |
| FE 201836 350 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 4 | 5.851 odd of response |
| FE 201836 250 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 4 | 0.634 odd of response |
| FE 201836 150 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 4 | 0.534 odd of response |
| FE 201836 100 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 4 | 1.760 odd of response |
| FE 201836 50 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 4 | 0.683 odd of response |
| Placebo (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 4 | 1.235 odd of response |
p-value: 0.93795% CI: [0.47, 2.005]Regression, Logistic
p-value: 0.02895% CI: [1.183, 18.968]Regression, Logistic
p-value: 0.16695% CI: [0.2, 1.318]Regression, Logistic
p-value: 0.17495% CI: [0.129, 1.447]Regression, Logistic
p-value: 0.60895% CI: [0.369, 5.512]Regression, Logistic
p-value: 0.17195% CI: [0.237, 1.292]Regression, Logistic
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%).
Time frame: Week 8
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 8 | 1.395 odd of response |
| FE 201836 350 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 8 | 3.398 odd of response |
| FE 201836 250 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 8 | 1.928 odd of response |
| FE 201836 150 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 8 | 0.877 odd of response |
| FE 201836 100 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 8 | 1.039 odd of response |
| FE 201836 50 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 8 | 1.489 odd of response |
| Placebo (Randomized Treatment Period) | Responder Rate in Nocturnal Voids at Week 8 | 1.503 odd of response |
p-value: 0.8595% CI: [0.43, 2.003]Regression, Logistic
p-value: 0.1595% CI: [0.745, 6.862]Regression, Logistic
p-value: 0.63295% CI: [0.462, 3.566]Regression, Logistic
p-value: 0.36395% CI: [0.183, 1.863]Regression, Logistic
p-value: 0.55595% CI: [0.203, 2.359]Regression, Logistic
p-value: 0.98495% CI: [0.408, 2.405]Regression, Logistic
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%).
Time frame: During 12 weeks of treatment
Population: The ITT-RT comprised of all the subjects randomized at Visit 4.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FE 201836 500 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids During 12 Weeks of Treatment | 1.129 odd of response |
| FE 201836 350 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids During 12 Weeks of Treatment | 1.095 odd of response |
| FE 201836 250 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids During 12 Weeks of Treatment | 1.032 odd of response |
| FE 201836 150 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids During 12 Weeks of Treatment | 0.934 odd of response |
| FE 201836 100 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids During 12 Weeks of Treatment | 0.887 odd of response |
| FE 201836 50 ug (Randomized Treatment Period) | Responder Rate in Nocturnal Voids During 12 Weeks of Treatment | 0.849 odd of response |
| Placebo (Randomized Treatment Period) | Responder Rate in Nocturnal Voids During 12 Weeks of Treatment | 0.834 odd of response |
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [0.868, 2.597]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [0.905, 2.45]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [0.927, 2.264]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [0.957, 1.896]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [0.972, 1.638]
Comparison: Based on a Bayesian analysis of a sigmoidal dose-response relationship.95% CI: [0.991, 1.313]