Study to Evaluate Armodafinil Treatment in Improving Prefrontal Cortical Activation and Working Memory Performance

NCT00711516 | Completed Phase 4 Results

• 1 other identifier: C10953/4026/AP/US
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 9

Brief Summary

The primary objective of this study is to determine whether treatment with armodafinil will provide improvements in prefrontal cortical activation in patients with OSAHS (Obstructive Sleep Apnea/Hypopnea Syndrome) who have residual sleepiness despite receiving nCPAP therapy.

Conditions

Excessive Sleepiness

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Endpoint in Number of Contiguous Activated Voxels Meeting Predefined Threshold in Dorsolateral Prefrontal Cortex (DLPFC) on Functional Magnetic Resonance Imaging (fMRI) as a Measure of Prefrontal Cortical Activation

  The primary outcome was the change from baseline in number of contiguous activated voxels in the dorsolateral prefrontal cortex (DLPFC) on functional magnetic resonance imaging (fMRI) at Week 2(or last observation after baseline). Each voxel is compared to the reference wave form. If it differs from that value p\<0.05, the voxel is considered active. fMRI is a brain imaging technique that identifies neuronal activation related to specific tasks or sensory stimulation. Increased neuronal activity increases blood flow and oxygen content to the activated part of the brain, altering fMRI signal.

  Baseline and Endpoint (Week 2 or last observation after baseline)

Secondary Outcomes (44)

• Change From Baseline to Endpoint in Mean Response Latency in the 2-Back Working Memory Test at Endpoint - Mean Performance Speed

  Baseline and Endpoint (Week 2 or last observation after baseline)

• Change From Baseline to Endpoint in the Number of Contiguous Activated Voxels Meeting the Predefined Threshold in the Anterior Cingulate Cortex (ACC)

  Baseline and Endpoint (Week 2 or last observation after baseline)

• Change From Baseline to Endpoint in the Number of Contiguous Voxels Meeting the Predefined Threshold in the Posterior Parietal Cortex (PPC)

  Baseline and Endpoint (Week 2 or last observation after baseline)

• Change From Baseline to Endpoint in the Number of Contiguous Activated Voxels Meeting the Predefined Threshold in the Thalamus

  Baseline and Endpoint (Week 2 or last observation after baseline)

• Pattern Recognition Memory (PRM) Percent Correct (Immediate) From the CANTAB Battery-Change From Baseline to Endpoint

  Baseline and Endpoint (Week 2 or last observation after baseline)

Study Arms (2)

1

EXPERIMENTAL

Armodafinil treatment (200 mg/day) - Study drug was supplied as 50 mg tablets and the dose was titrated from a starting dose of 50 mg taken once daily in the morning (before 0800), increasing to 100 mg/day on Day 2, 150 mg/day on day 5, and then 200 mg/day beginning Day 8 and continuing through the end of the two week double-blind treatment period.

Drug: Armodafinil

2

PLACEBO COMPARATOR

Placebo comparator - Placebo tablets matching the armodafinil 50 mg tablets drug were supplied and the dose was titrated from a starting dose of one tablet taken once daily in the morning (before 0800), increasing to two tablets/day on Day 2, three tablets/day on day 5, and then four tablets/day beginning Day 8 and continuing through the end of the two week double-blind treatment period.

Drug: Placebo

Interventions

Armodafinil DRUG

Armodafinil once-daily (50 mg/day (1 tablet) on Day 1; increased to 100 mg/day (2 tablets) starting on Day 2; increased to 150 mg/day (3 tablets) starting on Day 5; increased to 200 mg/day (4 tablets) starting on Day 8). Then continue 200 mg/day dosage through Day 14.

1

Placebo DRUG

Matching Placebo dosed once-daily (50 mg/day (1 tablet) on Day 1; increased to 100 mg/day (2 tablets) starting on Day 2; increased to 150 mg/day (3 tablets) starting on Day 5; increased to 200 mg/day (4 tablets) starting on Day 8). Then continue 200 mg/day dosage through Day 14.

2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient has a current diagnosis of OSAHS and has a complaint of excessive sleepiness despite effective nCPAP therapy.
• Patient has excessive sleepiness as evidenced by a mean sleep latency of less than 8 minutes, as determined by the MSLT.
• Patient has an ESS score of 10 or more at the initial screening visit.
• Patient has a habitual sleep time beginning no earlier than 2100 and ending no later than 0700.
• Patient is right-handed. Patients who are ambidextrous may be eligible following consultation with the medical monitor.
• Women of childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study.
• Patient exhibits reasonable accuracy (≥80%) on the 2-back working memory task during the training session at the second screening visit.

You may not qualify if:

• The Patient:
• The patient is a current smoker or has a prior history of smoking (defined as ≥1 pack-year) within 2 years prior to the screening visit.
• consumes caffeine including coffee, tea and/or other caffeine-containing beverages or food averaging more than 400 mg of caffeine per day (approximately equivalent to 4 or more cups of coffee).
• has a clinically significant, uncontrolled medical or psychiatric conditions (treated or untreated).
• has a confirmed or probable diagnosis of a current sleep disorder other than OSAHS.
• has used any excluded prescription drugs or procedures for prohibited and allowed drugs within the excluded timeframe.
• has a history of alcohol, narcotic, or any other drug abuse.
• has a positive UDS, without medical explanation, at the screening visit.
• has a clinically significant deviation from normal in the physical examination.
• is a pregnant or lactating woman. Any woman becoming pregnant during the study will be withdrawn from the study.
• has a past or present seizure disorder, head trauma that is clinically significant, or past neurosurgery.
• has used an investigational drug within 1 month before the screening visit.
• has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
• has a known hypersensitivity to armodafinil or modafinil, or any other component of the study drug tablets.
• has a history of any clinically significant cutaneous drug reaction, or a history of clinically significant hypersensitivity reaction, including multiple allergies or drug reactions.

Sponsors & Collaborators

• Cephalon: lead

Study Sites (9)

Peninsula Sleep Center

Burlingame, California, 94010, United States

Location

Pacific Research

San Diego, California, 92103, United States

Location

VA San Diego Healthcare System

San Diego, California, 92161, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Beth Israel Deaconess Medical

Boston, Massachusetts, 12215, United States

Location

Neurocare, Inc.

Newton, Massachusetts, 02459, United States

Location

Washington University

St Louis, Missouri, 63108, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Research Associates

Raleigh, North Carolina, 27612, United States

Location

Related Publications (1)

• Greve DN, Duntley SP, Larson-Prior L, Krystal AD, Diaz MT, Drummond SP, Thein SG, Kushida CA, Yang R, Thomas RJ. Effect of armodafinil on cortical activity and working memory in patients with residual excessive sleepiness associated with CPAP-Treated OSA: a multicenter fMRI study. J Clin Sleep Med. 2014 Feb 15;10(2):143-53. doi: 10.5664/jcsm.3440.

  PMID: 24532997 DERIVED

MeSH Terms

Conditions

Disorders of Excessive Somnolence

Interventions

Modafinil

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Sponsor's Medical Expert, Clinical Research
• Organization: Cephalon, Inc.

1-800-896-5855

Study Officials

• Sponsor's Medical Expert

  Cephalon

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2008
• First Posted: July 9, 2008
• Study Start: September 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: October 1, 2009
• Last Updated: July 19, 2013
• Results First Posted: February 14, 2011

Record last verified: 2013-07

Locations

US (9)