Study Investigating the Impact Burden of Nocturia Using the Nocturia Impact Diary

NCT01552343 | Completed Phase 3 Results

• 1 other identifier: 000034
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to assess psychometric properties (reliability and validity) of the Nocturia Impact (NI) diary. To assess the association between reduction of number of nocturnal voids and the mean changes in NI scores (sensitivity of the NI total score to change in nocturia). To assess which NI diary items account for the main difference in change in total NI score in treatment versus placebo.

Conditions

Nocturia

Outcome Measures

Primary Outcomes (3)

• The Pearson Correlation Coefficient Between Change From Baseline to Month 1 in Number of Nocturnal Voids and Change From Baseline to Month 1 in Nocturia Impact (NI) Diary Total Score

  This outcome is a measure of sensitivity of the NI Diary to change in nocturia. The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). Responses are scored from 0 (no impact) to 4 (highest impact); a lowering of score equals a decrease in impact caused by nocturia. The NI total score is the sum of the 11 core items scores. The NI total score was analyzable only if all 11 items (Q1-Q11) had non-missing responses. Otherwise, it was defined as missing. Missing values were not imputed. The average over the 3-day diary period prior to baseline (Day 1) and Month 1 was used for the overall impact score. The correlation was estimated using Fisher's z transformation, i.e. the NI total score was based on a standardized scale from 0 (lowest impact) to 100 (highest impact). Corresponding adjusted partial correlation coefficients were based on adjustments for mean number of Baseline voids, Baseline NI total score, age, and gender.

  Day 1 (Baseline), Month 1

• Difference in Mean Change From Baseline to Month 1 in Nocturia Impact (NI) Total Scores and Overall Impact Question for Responders and Non-Responders

  This outcome is a measure of sensitivity of the NI Diary to change in nocturia. The NI Diary is a 12-item instrument consisting of 11 core items and an overall impact question (Q12). The NI total score is defined as the sum of the 11 core items scores. The overall impact question (Q12) and the NI total score were transformed using Fisher's z transformation, i.e. the scores were based on a standardized scale from 0 (lowest impact) to 100 (highest impact). The difference in mean change in NI total score for subjects who experienced a reduction from baseline of \<33% in nocturnal voids at the Month 1 visit (non-responders) versus those with a reduction in nocturnal voids from Baseline of ≥33% (responders) was estimated.

  Day 1 (Baseline), Month 1

• Cohen's D Effect Size in Responsiveness in the Nocturia Impact (NI) Total Scores and Overall Impact Question as Measured From Baseline (Day 1) to Month 1

  The responsiveness of the NI Diary was measured with Cohen's D effect size. The effect size was calculated for active treatment versus placebo, based on change from Baseline to Month 1. The effect size was evaluated as "small," "medium," or "large" if D was \<=0.35, \>0.35 - 0.65, or \>0.65, respectively. Mean values are the Cohen's D effect size. Standard deviation is the pooled standard deviation.

  Day 1 (Baseline), Month 1

Secondary Outcomes (5)

• Internal Consistency of the Nocturia Impact (NI) Total Score for Each Day NI Diaries Were Completed Assessed as Cronbach's Alpha Values

  Screening (Day -20 to Day -18), Baseline (Day -2 to Day 1) and Treatment (Day 28 to Day 30)

• Construct Validity For the Nocturia Impact (NI) Total Scores and Overall Impact Question (Q12) for Participants With High/Low Number of Nocturnal Voids

  Screening (Day -20), Baseline (Day 1)

• Change From Baseline to Month 1 on Nocturia Impact (NI) Total Score

  Baseline (Day -2 to Day 1), Treatment (Day 28-30)

• Minimum Post-Treatment Serum Sodium Levels

  Day 1 up to 1 month

• Summary of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Day 1 up to 1 month

Study Arms (4)

Female - Desmopressin 25 μg

EXPERIMENTAL

Female participants took 1 tablet of 25 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.

Drug: Desmopressin

Female - Placebo

PLACEBO COMPARATOR

Female participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.

Drug: Placebo

Male - Desmopressin 75 μg

EXPERIMENTAL

Male participants took 1 tablet 75 μg every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.

Drug: Desmopressin

Male - Placebo

PLACEBO COMPARATOR

Male participants took 1 tablet of placebo every night, approximately 1 hour prior to bedtime (with the intention to sleep), for a period of 1 month.

Drug: Placebo

Interventions

Desmopressin DRUG

Desmopressin orally disintegrating tablets. Female participants took a 25 μg tablet and male participants took a 75 μg tablet one hour prior to bedtime for one month.

Also known as: FE992026, MINIRIN®, Nocturin®

Female - Desmopressin 25 μg; Male - Desmopressin 75 μg

Placebo DRUG

Placebo to match the 25 μg tablet of active drug taken by female participants or the 75 μg tablet taken by males. One placebo tablet taken one hour prior to bedtime for one month.

Female - Placebo; Male - Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent prior to performance of any study-related activity
• years of age (at the time of written consent) or older
• Previous participation in FE992026 CS40 or FE992026 CS41 with a completion ≥ 30 days prior to Screening. The subject should have responded to active treatment during FE992026 CS40 or FE992026 CS41 or if he/she received placebo during these two studies he/she should have been a non-responder.
• At least two nocturnal voids every night in two consecutive 3-day periods during the screening period (as determined by the two night-time voiding diaries dispensed at Visit 1 and collected at Visit 2)

You may not qualify if:

• Chronic prostatitis (males)/chronic pelvic pain syndrome (CPPS)
• Suspicion of bladder outlet obstruction (BOO) or a urine flow of \< 5 mL/s as confirmed by uroflowmetry performed after suspicion of BOO
• Surgical treatment, including transurethral resection, for BOO or benign prostatic hyperplasia (males) within the past six months
• Urinary retention or a post void residual volume \> 150 mL for females and \> 250 mL for males as confirmed by bladder ultrasound performed after suspicion of urinary retention
• Central or nephrogenic diabetes insipidus
• Syndrome of inappropriate antidiuretic hormone
• Current or a history of urologic malignancies e.g. bladder cancer
• Genito-urinary tract pathology e.g. infection or stone in the bladder and urethra causing symptoms
• Neurogenic detrusor activity (detrusor overactivity)
• Suspicion or evidence of cardiac failure
• Chronic prostatitis (males)/chronic pelvic pain syndrome (CPPS)
• Uncontrolled hypertension
• Uncontrolled diabetes mellitus
• Hyponatraemia: serum sodium level must be within normal limits
• Renal insufficiency: Serum creatinine must be within normal limits and estimated glomerular filtration rate must be ≥ 50 mL/min

Sponsors & Collaborators

• Ferring Pharmaceuticals: lead

Study Sites (10)

South Florida Medical Research

Aventura, Florida, United States

Location

Avail Clinical Research, LLC

DeLand, Florida, United States

Location

Accelovance

Peoria, Illinois, United States

Location

DM Clinical Research

Springfield, Massachusetts, United States

Location

Beyer Research

Kalamazoo, Michigan, United States

Location

Remedica LLC

Rochester, Michigan, United States

Location

Accumed Research Associates

Garden City, New York, United States

Location

Radiant Research, Inc.

Greer, South Carolina, United States

Location

Quality Research, Inc.

San Antonio, Texas, United States

Location

Radiant Research, Inc.

San Antonio, Texas, United States

Location

Related Publications (1)

• Holm-Larsen T, Andersson F, van der Meulen E, Yankov V, Rosen RC, Norgaard JP. The Nocturia Impact Diary: a self-reported impact measure to complement the voiding diary. Value Health. 2014 Sep;17(6):696-706. doi: 10.1016/j.jval.2014.06.007. Epub 2014 Aug 20.

  PMID: 25236993 RESULT

MeSH Terms

Conditions

Nocturia

Interventions

Deamino Arginine Vasopressin

Condition Hierarchy (Ancestors)

Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Arginine Vasopressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Limitations and Caveats

This was a patient reported outcome (PRO) validation study on a highly selective population (responders on active treatment and non-responsers on placebo from CS40/CS41) and not powered to look at efficacy.

Results Point of Contact

• Title: Clinical Development Support
• Organization: Ferring Pharmaceuticals

DK0-Disclosure@ferring.com

Study Officials

• Clinical Development Support

  Ferring Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2012
• First Posted: March 13, 2012
• Study Start: March 1, 2012
• Primary Completion: May 1, 2012
• Study Completion: June 1, 2012
• Last Updated: July 11, 2017
• Results First Posted: May 5, 2017

Record last verified: 2017-06

Locations

US (10)