Armodafinil for Patients Starting Hepatitis C Virus Treatment

• Sponsor: Research Foundation for Mental Hygiene, Inc. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01470651
• Collaborator: Icahn School of Medicine at Mount Sinai (Other), Weill Medical College of Cornell University (Other)
• Enrollment: 26
• Locations: 2
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 13
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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 Design

• Study Type: Interventional
• 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: Oct 1, 2011
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Armodafinil Active medication	Drug: Armodafinil; 50mg - 250mg pills, taken each morning, for 14 weeks; Other Names: 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 Names: Placebo Comparator

Outcome Measures

Primary Outcome Measures

1. Adherence to Medications Form [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) [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai Medical Center	New York City	New York	United States	10029
2	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

Investigators

• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Judith G. Rabkin, PhD, Research Scientist VI, Research Foundation for Mental Hygiene, Inc.
• ClinicalTrials.gov Identifier: NCT01470651
• Other Study ID Numbers: C10953/6285
• First Posted: Nov 11, 2011
• Last Update Posted: Feb 10, 2017
• Last Verified: Oct 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Judith G. Rabkin, PhD, Research Scientist VI, Research Foundation for Mental Hygiene, Inc.: HCV+; HCV treatment; Fatigue; patients starting alpha interferon/ribavirin treatment
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Modafinil

Study Results

Participant Flow

Arm/Group Title	Armodafinil	Sugar Pill
Arm/Group Description	Active medication Armodafinil: 50mg - 250mg pills, taken each morning, for 14 weeks	Inactive pill, matched to look like active medication Placebo Comparator: Inactive pill, matched to look like active medication
Period Title: Overall Study
STARTED	13	13
COMPLETED	6	10
NOT COMPLETED	7	3

Baseline Characteristics

Arm/Group Title	Armodafinil	Sugar Pill	Total
Arm/Group Description	Active medication Armodafinil: 50mg - 250mg pills, taken each morning, for 14 weeks	Inactive pill, matched to look like active medication Placebo Comparator: Inactive pill, matched to look like active medication	Total of all reporting groups
Overall Participants	13	13	26
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 92.3%	10 76.9%	22 84.6%
>=65 years	1 7.7%	3 23.1%	4 15.4%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53.77	57.23	55.5
Gender (Count of Participants)
Female	3 23.1%	3 23.1%	6 23.1%
Male	10 76.9%	10 76.9%	20 76.9%
Region of Enrollment (participants) [Number]
United States	13 100%	13 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Adherence to Medications Form
Description	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.
Time Frame	HCV medication adherence reported at 12 weeks

Outcome Measure Data

Analysis Population Description

Not all patients were given all medications, subjects are not factored in if they were not told to take a given drug.

Arm/Group Title	Armodafinil	Sugar Pill
Arm/Group Description	Active medication Armodafinil: 50mg - 250mg pills, taken each morning, for 14 weeks	Inactive pill, matched to look like active medication Placebo Comparator: Inactive pill, matched to look like active medication
Measure Participants	6	10
pegylated interferon	0 (0)	1.74 (1.16)
ribavirin	0 (0)	3.24 (1.87)
Incivek (or Victrelis)	4.95 (3.06)	2.88 (1.14)
Armodafinil or Placebo	14.00 (9.34)	8.02 (4.23)

2. Secondary Outcome

Title	Fatigue Severity Scale (FSS)
Description	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.
Time Frame	Biweekly for the first month, monthly thereafter

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil	Sugar Pill
Arm/Group Description	Active medication Armodafinil: 50mg - 250mg pills, taken each morning, for 14 weeks	Inactive pill, matched to look like active medication Placebo Comparator: Inactive pill, matched to look like active medication
Measure Participants	6	10
Baseline	23.29 (17.17)	26.90 (15.34)
Week 2	30.71 (16.16)	36.60 (17.37)
Week 4	37.14 (17.58)	38.90 (15.26)
Week 8	32.00 (20.93)	40.00 (18.06)
Week 12	31.71 (20.15)	38.40 (16.290)

Adverse Events

Time Frame	Baseline readings were collected two weeks before randomization to placebo or Armodafinil until 16 weeks after randomization. Measurements weekly until post-randomization week 12 at which point they were taken every other week.
Adverse Event Reporting Description	Side effects form listed: Nervousness, Irritability, Headaches, Nausea, Insomnia, Shortness of Breath, Difficulty Concentrating, Appetite/weight loss, Taste change, Dry mouth, Diarrhea, muscle aches, rash, fever, rectal pain, and two "other" fields. Side effect onset was defined as a two point increase (on a 5 point scale) from baseline.
Arm/Group Title	Armodafinil		Sugar Pill
Arm/Group Description	Active medication Armodafinil: 50mg - 250mg pills, taken each morning, for 14 weeks		Inactive pill, matched to look like active medication Placebo Comparator: Inactive pill, matched to look like active medication
All Cause Mortality
	Armodafinil		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Armodafinil		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Armodafinil		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)		13/13 (100%)
Cardiac disorders
Chest Pain	0/13 (0%)		1/13 (7.7%)
Eye disorders
Swollen Eyes	1/13 (7.7%)		0/13 (0%)
Gastrointestinal disorders
Diarrhea	5/13 (38.5%)		6/13 (46.2%)
Rectal Pain	3/13 (23.1%)		8/13 (61.5%)
Nausea	7/13 (53.8%)		7/13 (53.8%)
Constipation	0/13 (0%)		2/13 (15.4%)
Stomach pain	0/13 (0%)		1/13 (7.7%)
Altered Sense of Smell	0/13 (0%)		1/13 (7.7%)
General disorders
Sore Throat	1/13 (7.7%)		0/13 (0%)
Immune system disorders
Fever	5/13 (38.5%)		10/13 (76.9%)
Allergy Symptoms	0/13 (0%)		1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Muscle Pain	3/13 (23.1%)		5/13 (38.5%)
Plantar Fascitis	1/13 (7.7%)		0/13 (0%)
Weakness	1/13 (7.7%)		0/13 (0%)
Nervous system disorders
Shortness of Breath	5/13 (38.5%)		9/13 (69.2%)
Appetite or weight change	8/13 (61.5%)		10/13 (76.9%)
Taste Change	5/13 (38.5%)		10/13 (76.9%)
Dry Mouth	8/13 (61.5%)		8/13 (61.5%)
Headaches	9/13 (69.2%)		10/13 (76.9%)
Dizzyness	2/13 (15.4%)		3/13 (23.1%)
Tingling Feeling	1/13 (7.7%)		0/13 (0%)
feeling cold	0/13 (0%)		1/13 (7.7%)
Psychiatric disorders
Nervousness	4/12 (33.3%)		3/13 (23.1%)
Insomnia	3/12 (25%)		6/13 (46.2%)
Irritability	7/13 (53.8%)		10/13 (76.9%)
Difficulty in Concentration	6/13 (46.2%)		6/13 (46.2%)
Emotional instability	0/13 (0%)		1/13 (7.7%)
Reproductive system and breast disorders
Testicular Pain	0/13 (0%)		1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Cough	1/13 (7.7%)		1/13 (7.7%)
Skin and subcutaneous tissue disorders
Rash	7/13 (53.8%)		11/13 (84.6%)
Vascular disorders
Lightheadedness	0/13 (0%)		1/13 (7.7%)

Limitations/Caveats

It is difficult to attribute side effects to Armodafinil or placebo given patients were undergoing Hepatitis C Treatment throughout the trial.

More Information

Certain Agreements

Principal Investigators are NOT 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.