An Extension Study Investigating the Efficacy and Safety of a Fast-Dissolving (Melt) Formulation of Desmopressin for the Treatment of Nocturia in Adults

Participants completed a sleep diary on 3 consecutive mornings prior to each study visit, from which the initial period of undisturbed sleep was calculated and averaged for the 3 days. The Initial Period of Undisturbed Sleep is the time elapsed from bedtime to either first void or morning arising minus the minutes it took to fall asleep. Baseline refers to Baseline of Study CS29 and the number of weeks represents the total exposure to study drug. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29 and Weeks 8, 12, 20, 28, 52-56, 72-76, and 92-96.

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

Participants completed a voiding diary for 3 consecutive 24-hour periods prior to the study visit in which they recorded each nocturnal urination (void). The mean number of voids per night was the average number of voids from the 3-day diary. Baseline refers to Baseline of Study CS29 and the number of weeks represents the total exposure to study drug. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29 and Weeks 8, 12, 20, 28, 52-56, 72-76, and 92-96.

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

Percentage of participants with \>33% reduction from Baseline in the mean number of nocturnal urinations per night, calculated from the 3-day voiding diary completed prior to each study visit. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29 and Weeks 8, 12, 20, 28, 52-56, 72-76, and 92-96.

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

The ICIQ-N is a self-administered 4-item questionnaire designed to assess the frequency and bother of daytime and nighttime urination. To assess nighttime urination bother, participants were asked to rate the degree of bother of nighttime urination by answering the question Night time urination: How much does this bother you? on a scale ranging from 0 (not at all) to 10 (a great deal). Higher numbers indicate greater bother. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months)

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

The NQoL is a self-administered 13-item questionnaire designed to assess the impact of nocturia on quality of life. It contains a sleep/energy domain (6 questions), a bother/concern domain (6 questions), and 1 global QoL question (which is not included in the overall score). The 12 core items are scored on a 0 to 4 scale, and the overall score is calculated by transforming the raw score into a 0-100 scale with higher numbers indicating better impact on quality of life. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months)

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

The NQoL is a self-administered 13-item questionnaire designed to assess the impact of nocturia on quality of life. It contains a sleep/energy domain (6 questions), a bother/concern domain (6 questions), and 1 global QoL question. The 12 core items are scored on a 0 to 4 scale with higher numbers indicating a better quality of life. The sleep/energy domain summary score is calculated by transforming the raw score into a 0-100 scale with higher numbers indicating a better impact on quality of life. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months)

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

The NQoL is a self-administered 13-item questionnaire designed to assess the impact of nocturia on quality of life. It contains a sleep/energy domain (6 questions), a bother/concern domain (6 questions), and 1 global QoL question. The 12 core items are scored on a 0 to 4 scale with higher numbers indicating a better quality of life. The bother/concern domain summary score is calculated by transforming the raw score into a 0-100 scale with higher numbers indicating a better impact on quality of life. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months)

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

The PSQI is a self-administered 19-item questionnaire designed to assess sleep quality and disturbances. The 19 individual items are scored on an evenly weighted 0 to 3 scale and generate 7 component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score ranging from 0 to 21. Higher numbers indicate greater sleep disturbance. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months)

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

The NQoL is a self-administered 13-item questionnaire designed to assess the impact of nocturia on quality of life. It contains a sleep/energy domain (6 questions), a bother/concern domain (6 questions), and 1 global QoL question. The global QoL question is scored on a scale ranging from 0 (not at all) to 10 (a great deal). Higher numbers indicate better impact on quality of life. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months)

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

The SF-12v2 was used to measure the impact of nocturia and lack of sleep on general quality of life. The SF-12 consists of 12 questions spanning 8 domains: physical functioning, role function-physical, role function-emotional, bodily pain, general health, vitality, social functioning, and mental health. These scales are combined to create 2 summary measures: the Physical Health Summary and Mental Health Summary. The Mental Health Summary score ranges from 0 to 100, where higher numbers indicate better quality of life. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months)

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

The SF-12v2 was used to measure the impact of nocturia and lack of sleep on general quality of life. The SF-12 consists of 12 questions spanning 8 domains: physical functioning, role function-physical, role function-emotional, bodily pain, general health, vitality, social functioning, and mental health. These scales are combined to create 2 summary measures: the Physical Health Summary and Mental Health Summary. The Physical Health Summary score ranges from 0 to 100, where higher numbers indicate better quality of life. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29, Week 16, Visit 12 (approximately 56-78 weeks total study time) and End of Study (up to a maximum of 35 months)

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

Participants completed a sleep diary on 3 consecutive mornings prior to each study visit, from which the total sleep time was calculated and averaged for the 3 days. Baseline refers to Baseline of Study CS29 and the number of weeks represents the total exposure to study drug. Participants in the 10μg arm are included only until the time of dose escalation.

Time frame: Baseline of Study CS29 and Weeks 8, 12, 20, 28, 52-56, 72-76, and 92-96.

Population: Efficacy Analysis dataset = CS29 ITT population (all randomized patients who received \>=1 dose of study drug and provided \>=1 primary efficacy measure during Part I) who were on active treatment. # analyzed represents baseline participants. N= indicates # of participants for whom data were also available at the post-baseline time point.

An AE was any untoward medical occurrence that did not necessarily have a causal relationship with the study drug. An adverse drug reaction (ADR) was an AE evaluated by the Investigator as being probably or possibly causally related to treatment with the study drug. A serious AE (SAE) was any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or congenital anomaly/birth defect or was an important medical event that could have jeopardized the patient's safety or required medical or surgical intervention to prevent 1 of the outcomes listed above. The intensity of an AE was defined as severe if it resulted in the inability to work or perform usual activities.

Time frame: From first dose of study drug in Study CS29 until the end of study CS31 (up to 35 months).

Population: Safety dataset included all patients who received at least 1 dose of study drug in either Study CS29 or CS31 and counted patients according to their study drug exposure; therefore patients could be included in more than 1 treatment arm. Of the 1023 patients, 799 were unique patients enrolled in CS29, 222 were re-randomized and 2 had dose decreased.