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

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02151253
• Collaborator: (none)
• Enrollment: 81
• Location: 1
• Arms: 2
• Duration (Months): 52
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Nocturia; Daytime Sleepiness	Drug: Armodafinil; Drug: Placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled, Cross-over Study of Armodafinil Treatment of Daytime Sleepiness Associated With Treated Nocturia
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Epworth Sleepiness Scale [ESS] [Baseline, Week 4 of each phase]

   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.

Secondary Outcome Measures

1. Clinical Global Impressions, Change in Severity of Excessive Daytime Sleepiness (EDS) [week 4, of each phase]

   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"

2. Mean Number of Naps/Day [week 4 of each phase.]

   measurements are for the preceding week

3. Mean Number of Minutes Napped Per Day Based on Sleep Diary [week 4 of each phase.]

   measurements are for the preceding week

4. Mean Number of Nocturic Events (Episode of Urination Preceded and Followed by Sleep) [week 4 of each phase.]

   Nocturic Events is defined as an episode of urination preceded and followed by sleep. Measurements are for the preceding week

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Andrew Krystal, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02151253
• Other Study ID Numbers: Pro00028116
• First Posted: May 30, 2014
• Last Update Posted: Mar 24, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Duke University: Nocturia; Daytime sleepiness
• Additional relevant MeSH terms: Disorders of Excessive Somnolence; Sleepiness; Nocturia; Modafinil

Study Results

Participant Flow

Recruitment Details	Eighty-one individuals signed consent and were screened for entry into this study. Thirty of these subjects met the inclusion/exclusion criteria but only 28 subjects were randomized to the study. (2 subjects withdrew consent prior to randomization).

Arm/Group Title	Armodafinil First, Then Placebo	Placebo First, Then Armodafinil
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	13	15
COMPLETED	13	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Randomized Participants
Arm/Group Description
Overall Participants	28
Age, Customized (years) [Mean (Standard Deviation) ]
Between 18 and 90	54.5 (14.2)
Sex: Female, Male (Count of Participants)
Female	21 75%
Male	7 25%
Race/Ethnicity, Customized (participants) [Number]
African American	17 60.7%
Caucasian	9 32.1%
Asian	1 3.6%
Mixed Race	1 3.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Epworth Sleepiness Scale [ESS]
Description	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.
Time Frame	Baseline, Week 4 of each phase

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	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.	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.
Measure Participants	28	28
Mean (Standard Deviation) [units on a scale]	9.03 (5.18)	9.73 (4.43)

2. Secondary Outcome

Title	Clinical Global Impressions, Change in Severity of Excessive Daytime Sleepiness (EDS)
Description	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"
Time Frame	week 4, of each phase

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	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.	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.
Measure Participants	28	28
Mean (Standard Deviation) [units on a scale]	2.58 (1.03)	3.12 (0.82)

3. Secondary Outcome

Title	Mean Number of Naps/Day
Description	measurements are for the preceding week
Time Frame	week 4 of each phase.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	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.	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.
Measure Participants	28	28
Mean (Standard Deviation) [naps per day]	0.48 (0.71)	0.73 (1.20)

4. Secondary Outcome

Title	Mean Number of Minutes Napped Per Day Based on Sleep Diary
Description	measurements are for the preceding week
Time Frame	week 4 of each phase.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	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.	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.
Measure Participants	28	28
Mean (Standard Deviation) [minutes napped per day]	38.9 (65.1)	40.0 (61.3)

5. Secondary Outcome

Title	Mean Number of Nocturic Events (Episode of Urination Preceded and Followed by Sleep)
Description	Nocturic Events is defined as an episode of urination preceded and followed by sleep. Measurements are for the preceding week
Time Frame	week 4 of each phase.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	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.	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.
Measure Participants	28	28
Mean (Standard Deviation) [Nocturic Events]	1.6 (1.1)	1.89 (1.1)

Adverse Events

Arm/Group Title	Armodafinil		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/28 (39.3%)		10/28 (35.7%)
Gastrointestinal disorders
Nausea	1/28 (3.6%)		1/28 (3.6%)
General disorders
Dizziness	0/28 (0%)		1/28 (3.6%)
Psychiatric disorders
Anxiety/Jitteriness	4/28 (14.3%)		3/28 (10.7%)
insomnia	1/28 (3.6%)		0/28 (0%)
Renal and urinary disorders
Urinary Tract Infection	0/28 (0%)		1/28 (3.6%)
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection	4/28 (14.3%)		4/28 (14.3%)
Sinus Infection	1/28 (3.6%)		0/28 (0%)
Skin and subcutaneous tissue disorders
Rash	0/28 (0%)		1/28 (3.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.