Armodafinil for Patients Starting Hepatitis C Virus Treatment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01470651
Recruitment Status : Terminated (European Medicines Agency issued a drug/drug interaction: sofosbuvir/modafinil)
First Posted : November 11, 2011
Results First Posted : February 10, 2017
Last Update Posted : February 10, 2017
Icahn School of Medicine at Mount Sinai
Weill Medical College of Cornell University
Information provided by (Responsible Party):
Judith G. Rabkin, PhD, Research Foundation for Mental Hygiene, Inc.

Brief Summary:
Fatigue is one of the most common side effects of the treatment of hepatitis C infection with pegylated interferon and ribavirin, and is a major cause of treatment discontinuation. Armodafinil is an FDA approved stimulant medication for the treatment of narcolepsy and shift-work sleep disorder. This is a randomized placebo controlled study to determine whether patients assigned to armodafinil have fewer missed doses, dose reductions or treatment discontinuation due to side effects in the first 12 weeks of treatment for hepatitis C infection than do placebo patients. Placebo patients are offered 14 weeks of open label armodafinil after Week 12.

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: Armodafinil Drug: Sugar Pill Phase 4

Detailed Description:

Four million Americans have chronic hepatitis C (HCV), and 30% of HIV+ patients are co-infected with HCV. Until May 2011, the standard treatment for HCV was the combination of alpha interferon (injected weekly) and ribavirin (daily pills) (IFN/RBV) for 48 weeks in order to achieve sustained virologic remission (cure). HCV treatment initiation was low, often because of concern about severe treatment side effects as well as high rates of virologic failure. Among the minority of medically eligible HCV+ patients (with or without co-morbid HIV/AIDS) who actually began treatment with IFN/RBV, side effects cause substantial attrition (about 20% by Week 12, 40% by Week 24). The most common adverse events are flu-like symptoms, of which fatigue is most prominent. Depressed mood is also common (mostly somatic symptoms).

Two new medications, telaprevir and boceprevir (protease inhibitors) have been successful in treatment of HCV in clinical trials, and both were approved by the FDA for those patients with genotype 1 HCV, and are marketed as of May 2011. One of the new drugs will be added to the current regimen for genotype 1 infection. Because both drugs are protease inhibitors, which develop rapid resistance when administered alone, they must be added to the current standard of care rather than replace it. This is expected to vastly increase willingness of doctors to recommend treatment, and for patients to agree to treatment. The investigators expect that most hepatologists will recommend, and patients agree to the addition of one of these medications from now on. However, it should be noted that both commonly cause fatigue if it isn't already present because of HCV itself, or peginterferon or ribavirin. The major adverse event associated with telaprevir is rash, and with boceprevir, anemia.

This is a 14-week placebo controlled double blind trial of armodafinil for patients about to begin HCV treatment, starting armodafinil or placebo 2 weeks prior to initiation of HCV treatment. Patients are recruited from the hepatology clinics at the respective sites. Randomization is 1:1. Placebo patients who continue HCV treatment are offered 14 weeks of armodafinil starting at Week 12 of HCV treatment when the armodafinil/placebo blind is broken.

Patients will be seen weekly for the first 4 weeks to titrate armodafinil dose and manage side effects, if any, and then biweekly, with telephone contact on the intervening weeks through Week 12. After that, monthly telephone calls through Week 24 will be conducted with patients randomized to armodafinil, and biweekly visits with placebo patients beginning armodafinil at Week 12.

The primary outcome measures concern non-adherence to INF/RBV treatment: 1) missed doses; 2) dose reductions, and 3) attrition due to side effects. Secondary outcomes include ratings of fatigue on the Fatigue Severity Scale, depression on the Patient Health Questionnaire (PHQ-9), and quality of life on the Endicott Quality of Life Enjoyment and Satisfaction Questionnaire.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Armodafinil for Patients Starting Hepatitis C Treatment
Study Start Date : October 2011
Actual Primary Completion Date : June 2014
Actual Study Completion Date : June 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Armodafinil
Active medication
Drug: Armodafinil
50mg - 250mg pills, taken each morning, for 14 weeks
Other Name: Nuvigil

Placebo Comparator: Sugar pill
Inactive pill, matched to look like active medication
Drug: Sugar Pill
Inactive pill, matched to look like active medication
Other Name: Placebo Comparator

Primary Outcome Measures :
  1. Adherence to Medications Form [ Time Frame: HCV medication adherence reported at 12 weeks ]
    The Medication Adherence Form was designed to assess any HCV medication dosing changes, including discontinuation, and the reasons for the changes. The form asks specifically about the HCV medications: pegylated interferon, ribavirin and Incivek (or Victrelis), as well as the study medication, armodafinil.

Secondary Outcome Measures :
  1. Fatigue Severity Scale (FSS) [ Time Frame: Biweekly for the first month, monthly thereafter ]
    Fatigue Severity Scale is a 9-item scale measures the impact of fatigue on everyday functioning (e.g. "fatigue interferes with my work, family or social life"). Response format is a 7-point Likert scale of agreement with a 1-week time frame. Total score is the sum of item scores and ranges from 9 to 63 points, with higher scores indicating greater fatigue. A score greater than 40 is considered to be a clinically significant level of fatigue. Scores on the scale correlate highly with other measures of fatigue, is sensitive to change, and is routinely used in studies of modafinil/armodafinil.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • HCV+ patients medically cleared for IFN/RBV treatment -HIV+ or HIV-
  • Speaks English
  • Able and willing to give informed consent
  • Fecund women: use barrier method of contraception

Exclusion Criteria:

  • Untreated and uncontrolled hypertension
  • Left ventricular hypertrophy
  • Currently taking stimulant medication
  • Uncontrolled mental health problems including: MDD, suicidal or homicidal ideation, bipolar disorder, or schizophrenia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01470651

United States, New York
Mount Sinai Medical Center
New York City, New York, United States, 10029
New York-Presbyterian/Weill Cornell Medical Center
New York City, New York, United States, 10065
Sponsors and Collaborators
Research Foundation for Mental Hygiene, Inc.
Icahn School of Medicine at Mount Sinai
Weill Medical College of Cornell University
Principal Investigator: Jeffrey Weiss, Ph.D., MS Icahn School of Medicine at Mount Sinai
Principal Investigator: Stephen J. Ferrando, M.D. Weill Medical College of Cornell University

Responsible Party: Judith G. Rabkin, PhD, Research Scientist VI, Research Foundation for Mental Hygiene, Inc. Identifier: NCT01470651     History of Changes
Other Study ID Numbers: C10953/6285
First Posted: November 11, 2011    Key Record Dates
Results First Posted: February 10, 2017
Last Update Posted: February 10, 2017
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Judith G. Rabkin, PhD, Research Foundation for Mental Hygiene, Inc.:
HCV treatment
patients starting alpha interferon/ribavirin treatment

Additional relevant MeSH terms:
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Wakefulness-Promoting Agents
Central Nervous System Stimulants
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action