Comparative Trial to Investigate the Dose-Response of 4 Different Dose Levels of Minirin Melt and Placebo (NOC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ferring Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01184859
First received: August 18, 2010
Last updated: April 24, 2012
Last verified: April 2012
  Purpose

This is a multi-centre, randomised, placebo-controlled, double-blind, parallel-group comparative trial to be conducted in nocturia patients. The trial is designed to characterize the dose-response relationship of Minirin (desmopressin) Melt in order to establish correct dose recommendations in the target patient population. In particular, the trial is designed to link the duration of action to the clinical endpoint. Furthermore, the trial is designed to describe the safety of four different dose levels of desmopressin.


Condition Intervention Phase
Nocturia
Drug: Desmopressin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-centre, Double-blind, Randomised, Placebo-controlled, Parallel-group, Comparative Trial to Investigate the Dose-Response of 4 Different Dose Levels of Minirin Melt and Placebo in Water-loaded Male and Female Japanese Nocturia Patients (Single Dose), and to Study the Efficacy of 4 Different Dose Levels of Minirin Melt and Placebo After 28 Days of Dosing (Multiple Doses)

Resource links provided by NLM:


Further study details as provided by Ferring Pharmaceuticals:

Primary Outcome Measures:
  • Duration of Action Defined as the Time With Urine Osmolality Above 200 mOsm/kg - Period 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Participants were water-loaded to suppress the endogenous release of vasopressin, thus all antidiuretic activity was generated by desmopressin only. Water-loading was initiated 2 hours before dosing on Day 1. Urine volume was registered and samples for osmolality check were collected every 30 minutes as long as there was an antidiuretic action defined as a urine production <0.12 mL/kg/min. The hydration should have lasted until end of action, defined as when the urine production returned to >0.12 mL/kg/min, but no longer than 12 hours.

  • Change From Baseline in Number of Nocturnal Voids After 28 Days of Treatment - Period 2 [ Time Frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32 ] [ Designated as safety issue: No ]
    Records of nocturia and sleep over three consecutive days per week were kept in voiding-sleep diaries by study participants. The average number of nocturnal voids of the 3 days recorded in the last week of the study (between study days 25-32) was compared to average baseline readings.


Secondary Outcome Measures:
  • Area Under the Urine Osmolality Curve (AUCosm) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Area under the urine osmolality curve, from dose administration to end of action (AUCosm).

  • Area Under the Urine Production Curve (AUCurine Prod) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Area under the urine production curve, from dose administration to end of action (AUCurine prod)

  • Time When Urine Production <0.12 ml/kg/Min [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Urine volume was registered and samples for osmolality check were collected every 30 minutes as long as there was an antidiuretic action defined as a urine production <0.12 mL/kg/min. The hydration due to water-loading should have lasted until end of action, defined as when the urine production returned to >0.12 mL/kg/min, but no longer than 12 hours.

  • Change From Baseline in Duration of First Period of Undisturbed Sleep After 28 Days of Treatment - Period 2 [ Time Frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32 ] [ Designated as safety issue: No ]

    Duration of first period of undisturbed sleep is defined as the length of time from initial sleep to first awakening.

    Records of nocturia and sleep over three consecutive days per week were kept in voiding-sleep diaries by study participants. The average length of first period of undisturbed sleep of the 3 days recorded in the last week of the study (between study days 25-32) was compared to average baseline readings.


  • Change From Baseline in Total Sleep Time at Approximately Day 32 [ Time Frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32 ] [ Designated as safety issue: No ]

    Total sleep time is defined as the time spent asleep from initial sleep to final awakening.

    Records of nocturia and sleep over three consecutive days per week were kept in voiding-sleep diaries by study participants. The average of the total time asleep of the 3 days recorded in the last week of the study (between study days 25-32) was compared to average baseline readings.


  • Change From Baseline in Number of Daytime Voids at Approximately Day 32 [ Time Frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32 ] [ Designated as safety issue: No ]
    Number of daytime voids was recorded over three consecutive days per week in diaries kept by study participants. The average number of daytime voids of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

  • Change From Baseline in Number of 24-hour Urine Voids at Approximately Day 32 [ Time Frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32 ] [ Designated as safety issue: No ]
    Number of voids in 24 hours was recorded over three consecutive days per week in diaries kept by study participants. The average number of 24-hour voids of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

  • Change From Baseline in Nocturnal Urine Volume at Approximately Day 32 [ Time Frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32 ] [ Designated as safety issue: No ]
    Nocturnal urine volume was recorded over three consecutive days per week in diaries kept by study participants. The average nocturnal urine volume of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

  • Change From Baseline in 24-Hour Urine Volume at Approximately Day 32 [ Time Frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32 ] [ Designated as safety issue: No ]
    Twenty-four hour urine volume was recorded over three consecutive days per week in diaries kept by study participants. The average 24-hour urine volume of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

  • Change From Baseline in 24-Hour Urine Production Per Body Weight at Approximately Day 32 [ Time Frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32 ] [ Designated as safety issue: No ]
    Twenty-four hour urine volume was recorded over three consecutive days per week in diaries kept by study participants. Urine volume per body weight was calculated. The average 24-hour urine volume per kg of body weight of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

  • Change From Baseline in Nocturnal Polyuria Index at Approximately Day 32 [ Time Frame: 3 days between study days -6 to 0 (Baseline), and days 25 to 32 ] [ Designated as safety issue: No ]
    Nocturnal polyuria index is defined as a proportion of nocturnal urine volume to the 24-hour urine volume. Urine volume and time of day of those voids was recorded over three consecutive days per week in diaries kept by study participants. The average nocturnal polyuria index of the 3 days recorded in the last week of the study (between study days 25-32) was compared to the average baseline readings.

  • Change From Baseline in Nocturia-Related Quality of Life Based on Evaluation Provided by Nocturia Quality of Life Questionnaire (N-QoL) at Approximately Day 32 [ Time Frame: Approximately Day 4 (start of period 2) and Day 32 ] [ Designated as safety issue: No ]
    N-QoL assesses the impact of nocturia on quality of life (QoL) and treatment outcomes. N-QoL is a self-administered questionnaire with 13 items using scales of 0 = no negative impact to QoL to the upper number = signficant negative impact to QoL. The sleep/energy domain consists of 7 questions with a scale of 0 to 28. The bother/concern domain consists of 5 questions for a scale of 0 to 20. The 13th question is an overall assessment scored from 0 to 10. The Total Score includes all 13 questions with a scale of 0 (no negative impact to QoL) to 58 (significant negative impact to QoL).

  • Change From Baseline in Sleep Related Quality of Life Based on the Global Score of the Pittsburgh Sleep Quality Index (PSQI) at Approximately Day 32 [ Time Frame: Approximately Day 4 (start of period 2) and Day 32 ] [ Designated as safety issue: No ]
    The Global Score of the Pittsburgh Sleep Quality Index (PSQI) is comprised of Questions 2-9 with a total scale of 0 (no difficulty sleeping) to 21 (severe difficulty). The change in Global Score is Global Score at the end of period 2 (day 32) - Global Score at the start of Period 2 (day 4). A negative change indicates an improvement in quality of life.

  • Participant Counts of Minimum Observed Serum Sodium Levels During the Second Treatment Period (Days 4-32) [ Time Frame: Days 4- 32 ] [ Designated as safety issue: Yes ]
    Serum sodium levels were monitored throughout the trial as part of the clinical chemistry panel. If the value was ≤125 mEq/L, the participant was to be withdrawn from the trial and treatment stopped immediately. This outcome reports participants' lowest recorded serum sodium levels during the second treatment period.


Enrollment: 116
Study Start Date: July 2010
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Desmopressin 10µg
Study period 1: single dose of desmopressin 10µg. Study period 2: daily doses of desmopressin 10µg taken before bedtime for 28 days.
Drug: Desmopressin
Desmopressin oral lyophilisate melt tablet, in either the 10, 25, 50, or 100 μg dosage, for sublingual administration
Other Names:
  • FE992026
  • Minirin Melt
Experimental: Desmopressin 25µg
Study period 1: single dose of desmopressin 25µg. Study period 2: daily doses of desmopressin 25µg taken before bedtime for 28 days.
Drug: Desmopressin
Desmopressin oral lyophilisate melt tablet, in either the 10, 25, 50, or 100 μg dosage, for sublingual administration
Other Names:
  • FE992026
  • Minirin Melt
Experimental: Desmopressin 50µg
Study period 1: single dose of desmopressin 50µg. Study period 2: daily doses of desmopressin 50µg taken before bedtime for 28 days.
Drug: Desmopressin
Desmopressin oral lyophilisate melt tablet, in either the 10, 25, 50, or 100 μg dosage, for sublingual administration
Other Names:
  • FE992026
  • Minirin Melt
Experimental: Desmopressin 100µg
Study period 1: single dose of desmopressin 100µg. Study period 2: daily doses of desmopressin 100µg taken before bedtime for 28 days.
Drug: Desmopressin
Desmopressin oral lyophilisate melt tablet, in either the 10, 25, 50, or 100 μg dosage, for sublingual administration
Other Names:
  • FE992026
  • Minirin Melt
Placebo Comparator: Placebo
Study period 1: single dose of placebo. Study period 2: daily doses of placebo taken before bedtime for 28 days.
Drug: Placebo
Placebo melt tablet for sublingual administration
Other Name: placebo

  Eligibility

Ages Eligible for Study:   55 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Given written informed consent prior to any trial-related activity is performed
  • Aged 55-75 years
  • Mean number of nocturnal voids of at least two per night
  • Reached post-menopause (applicable to females only)

Exclusion Criteria:

  • Evidence of bladder outlet obstruction (BOO); or a urine flow of less than 5 mL/s (applicable to males only)
  • A surgical treatment for BOO or prostatic hyperplasia within the past 6 months (applicable to males only)
  • Showing symptoms of any of the following diseases and having a mean number of nocturnal voids exceeding four per night: Benign prostatic hyperplasia, overactive bladder, interstitial cystitis, severe stress urinary incontinence
  • Psychosomatic or habitual polydipsia
  • Urinary retention; or a post void residual volume in excess of 150 mL
  • A history or complication of urologic malignancy (e.g. bladder cancer or prostate cancer)
  • Complication of genito-urinary pathology (e.g. infection, stone, or neoplasia)
  • Complication of neurogenic detrusor activity
  • Complication or suspicion of heart failure
  • Uncontrolled hypertension
  • Uncontrolled diabetes mellitus
  • Complication of hepatobiliary disease
  • Abnormal serum creatinine level
  • Complication of hyponatraemia, or serum sodium level <135 mEq/L
  • Central or nephrogenic diabetes insipidus (CDI or NDI)
  • Syndrome of inappropriate antidiuretic hormone (SIADH)
  • Obstructive sleep apnea
  • Alcohol dependency or drug abuse
  • A job or lifestyle that may interfere with regular night-time sleep
  • Previous desmopressin treatment
  • Treatment with another investigational product within the past 3 months
  • A need for treatment with a prohibited concomitant drug for a complication or other problem
  • A mental condition, the lack of decision-making ability, dementia or a speech handicap
  • Any other reason that the Investigator believes inappropriate
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01184859

Locations
Japan
Japanese Red Cross Nagoya Daiichi Hospital
Nagoya, Aichi, Japan
National Center for Geriatrics and Gerontology
Obu, Aichi, Japan
Kokuho Asahi Central Hospital
Asahi, Chiba, Japan
University of Fukui Hospital
Yoshida, Fukui, Japan
Takayama Hospital
Chikushino, Fukuoka, Japan
Houshikai Group Kano Hospital
Koga, Fukuoka, Japan
St. Mary's Hospital
Kurume, Fukuoka, Japan
Jyusendo General Hospital
Koriyama, Fukushima, Japan
Social Insurance Nihonmatsu Hospital
Nihonmatsu, Fukushima, Japan
Takayama Clinic
Awagi, Hyogo, Japan
National Hospital Organization Kobe Medical Center
Kobe, Hyogo, Japan
Japanese Red Cross Mito Hospital
Mito, Ibaraki, Japan
Yokohama Shin-midori General Hospital
Yokohama, Kanagawa, Japan
Kumamoto Rosai Hospital
Yatsushiro, Kumamoto, Japan
Tohoku University Hospital
Sendai, Miyagi, Japan
Shinshu University Hospital
Matsumoto, Nagano, Japan
Senbokufujii Hospital
Sakai, Osaka, Japan
Kasukabe Chuo General Hospital
Kasukabe, Saitama, Japan
Hamamatsu University School of Medicine University Hospital
Hamamatsu, Shizuoka, Japan
Tokyo Women's Medical University Medical Center East
Arakawa, Tokyo, Japan
Koganeibashi Sakura Clinic
Koganei, Tokyo, Japan
Kunitachi Sakura Hospital
Kunitachi, Tokyo, Japan
University of Yamanashi Hospital
Chuo, Yamanashi, Japan
Harasanshin Hospital
Fukuoka, Japan
Saku Hospital
Fukuoka, Japan
Southwest Urological Clinic
Fukuoka, Japan
Yakuin Urogenital Hospital
Fukuoka, Japan
Saiseikai Fukushima General Hospital
Fukushima, Japan
Fukushima Red Cross Hospital
Fukushima, Japan
Ohara General Hospital
Fukushima, Japan
Jigenji Kubo Clinic
Kagoshima, Japan
Yagi Clinic
Kagoshima, Japan
Kawahara Hinyoukika
Kagoshima, Japan
Rakusai Newtown Hospital
Kyoto, Japan
Suzuki Urological Clinic
Nagano, Japan
Nanri Urological Clinic
Saga, Japan
Sponsors and Collaborators
Ferring Pharmaceuticals
Investigators
Study Director: Clinical Development Support Ferring Pharmaceuticals
  More Information

No publications provided

Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01184859     History of Changes
Other Study ID Numbers: FE992026 CS36
Study First Received: August 18, 2010
Results First Received: April 24, 2012
Last Updated: April 24, 2012
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Ferring Pharmaceuticals:
nocturia
bladder function

Additional relevant MeSH terms:
Nocturia
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Deamino Arginine Vasopressin
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 28, 2014