Cross-over Study of Armodafinil Treatment of Daytime Sleepiness Associated With Treated Nocturia

A Double-Blind, Placebo-Controlled, Cross-over Study of Armodafinil Treatment of Daytime Sleepiness Associated With Treated Nocturia

The objective of the study is to evaluate armodafinil as a wakefulness-promoting therapy as a means of improving residual daytime sleepiness in patients with treated nocturia.

Study Overview

• Status: Completed
• Conditions: Nocturia; Daytime Sleepiness
• Intervention / Treatment: Drug: Armodafinil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Receiving standard-of-care therapy for nocturia based on assessment by study physician
2. Evaluation by study physician indicates that the patient meets criteria for either overactive bladder diagnosis, or nocturnal polyuria diagnosis.
3. Mean number of nocturia episodes at least 2 per night based on day sleep/bladder diary
4. Epworth Sleepiness Scale Score of at least 10
5. Clinical Global Impression of Sleepiness at least Moderate
6. Age 18-90 years inclusive

Exclusion Criteria:

1. Medications affecting urinary or sleep-wake function other than therapy for OAB o or NP within 5 half-lives of baseline assessment
2. Sleep disorders other than nocturia based on history and screening assessment
3. Unstable medical or psychiatry conditions
4. Medical or psychiatric conditions affecting sleep/wake or urologic function
5. Apnea-Hypopnea Index (AHI) ≥ 15 on screening polysomnogram
6. Periodic Leg Movement Arousal Index (PLMAI) ≥ 15 on screening polysomnogram
7. History of substance abuse or dependence in the last year
8. Regular consumption of over 800 mg of caffeine use
9. Shift-work in the 3 months prior to or during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Armodafinil First, Then Placebo; During double-blind treatment subjects took armodafinil for 4 weeks before crossing over to placebo for 4 weeks. Pill is taken once daily, before 8 am. Armodafinil/placebo was initiated at a dose of 50 mg (1 tablet) and titrated to 150 mg after 1 week on the basis of the investigator's and patient's perception of efficacy and side-effects. After two weeks the medication could be increased to 250 mg or reduced back to 50 mg based on the investigator's and patient's perception of efficacy/side-effects. No increases in dosage were allowed after week 2. The dosage was decreased at a week 3 phone call if indicated on the basis of side-effects.	Drug: Armodafinil; Armodafinil 50 - 250 mg pills Subjects took armodafinil once daily, before 8 am. Armodafinil was initiated at a dose of 50 mg (1 tablet) and titrated to 150 mg after 1 week on the basis of the investigator's and patient's perception of efficacy and side-effects. After two weeks the medication could be increased to 250 mg or reduced back to 50 mg based on the investigator's and patient's perception of efficacy/side-effects. No increases in dosage were allowed after week 2. The dosage was decreased at a week 3 phone call if indicated on the basis of side-effects.; Drug: Placebo; Subject given placebo tablets to match Armodafinil pills. Subjects took placebo once daily, before 8 am. Placebo was initiated as 1 tablet and titrated to 3 tablets after 1 week on the basis of the investigator's and patient's perception of efficacy and side-effects. After two weeks the medication could be increased to 5 tablets or reduced back to 1 tablet based on the investigator's and patient's perception of efficacy/side-effects. No increases in dosage were allowed after week 2. The dosage was decreased at a week 3 phone call if indicated on the basis of side-effects.
Placebo Comparator: Placebo First, Then Armodafinil; During double-blind treatment subjects took placebo for 4 weeks before crossing over to armodafinil for 4 weeks. Pill is taken once daily, before 8 am. Armodafinil/placebo was initiated at a dose of 50 mg (1 tablet) and titrated to 150 mg after 1 week on the basis of the investigator's and patient's perception of efficacy and side-effects. After two weeks the medication could be increased to 250 mg or reduced back to 50 mg based on the investigator's and patient's perception of efficacy/side-effects. No increases in dosage were allowed after week 2. The dosage was decreased at a week 3 phone call if indicated on the basis of side-effects.	Drug: Armodafinil; Armodafinil 50 - 250 mg pills Subjects took armodafinil once daily, before 8 am. Armodafinil was initiated at a dose of 50 mg (1 tablet) and titrated to 150 mg after 1 week on the basis of the investigator's and patient's perception of efficacy and side-effects. After two weeks the medication could be increased to 250 mg or reduced back to 50 mg based on the investigator's and patient's perception of efficacy/side-effects. No increases in dosage were allowed after week 2. The dosage was decreased at a week 3 phone call if indicated on the basis of side-effects.; Drug: Placebo; Subject given placebo tablets to match Armodafinil pills. Subjects took placebo once daily, before 8 am. Placebo was initiated as 1 tablet and titrated to 3 tablets after 1 week on the basis of the investigator's and patient's perception of efficacy and side-effects. After two weeks the medication could be increased to 5 tablets or reduced back to 1 tablet based on the investigator's and patient's perception of efficacy/side-effects. No increases in dosage were allowed after week 2. The dosage was decreased at a week 3 phone call if indicated on the basis of side-effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Epworth Sleepiness Scale [ESS]	Epworth sleepiness scale (ESS) is measure of subjective sleepiness. Tendency to fall asleep in 8 situations. Total varies from zero to 24. A ESS of 10 or less is considered normal. Change is calculated as value at baseline minus value at week 4.	Baseline, Week 4 of each phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impressions, Change in Severity of Excessive Daytime Sleepiness (EDS)	Scale consists of a 7 point likert rating scale where the anchors were 1= "normal"; 2= "borderline sleepiness"; 3= "mild sleepiness"; 4= "moderate sleepiness"; 5= "marked sleepiness"; 6= "severe sleepiness"; and 7= "among the most extremely sleepy individuals"	week 4, of each phase
Mean Number of Naps/Day	measurements are for the preceding week	week 4 of each phase.
Mean Number of Minutes Napped Per Day Based on Sleep Diary	measurements are for the preceding week	week 4 of each phase.
Mean Number of Nocturic Events (Episode of Urination Preceded and Followed by Sleep)	Nocturic Events is defined as an episode of urination preceded and followed by sleep. Measurements are for the preceding week	week 4 of each phase.

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Andrew Krystal, MD, Duke University

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: May 28, 2014
• First Posted (Estimate): May 30, 2014

Study Record Updates

• Last Update Posted (Actual): March 24, 2017
• Last Update Submitted That Met QC Criteria: March 22, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Nocturia; Daytime sleepiness
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Lower Urinary Tract Symptoms; Urological Manifestations; Disorders of Excessive Somnolence; Sleepiness; Nocturia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: Pro00028116