Download Change in FACIT-F Total Score at Each Week

A Phase II, Randomized Placebocontrolled Trial of the Safety and Efficacy
of Stimulin as a New Treatment of Fatigue
and “Chemobrain” in Adult Cancer
Patients
Purpose of Study
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To evaluate the efficacy and safety
of Stimulin (POD, phunonadate) a
CNS stimulant, for the treatment of
fatigue and neurobehavioral
(cognitive) impairment associated
with chemotherapy
Study Objectives
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Primary objective
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Evaluate the efficacy of POD in the treatment of
chemotherapy-related fatigue in adult cancer
subjects using the FACIT-F
Secondary objectives
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Evaluate the efficacy of POD in improving
cognitive dysfunction
Explore the efficacious dose range required to
maintain effectiveness
Assess the safety of POD doses up to 50 mg/day
in this population
Patient Eligibility
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M/F, ages 18-70
Cancer dx, excl. 10 or metastatic brain tumors
4 cycles of cytotoxic chemotherapy (minimum),
completed > 2 months prior to study entry
Life expectancy >6 months
No focal neurological deficit
ECOG < 2
ICD-10 criteria for Cancer Related Fatigue
Mini-Mental Status Exam (MMSE) score > 20
Beck Depression Inventory-II (BD-II) score <18
Clinical Global Impression-Severity (CGI-S) score > 3
Proposed ICD-10 (1998) Criteria for
Cancer-Related Fatigue
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A1 Significant fatigue, diminished energy, or increased need to rest disproportionate to any recent
change in activity level
A2 Complaints of generalized weakness or limb heaviness
A3 Diminished concentration or attention
A4 Decreased motivation or interest to engage in usual activities
A5 Insomnia or hypersomnia
A6 Experience of sleep as unrefreshing or nonrestorative
A7 Perceived need to struggle to overcome inactivity
A8 Marked emotional reactivity (e.g. sadness, frustration, or irritability) to feeling fatigued
A9 Difficulty completing daily tasks attributed to feeling fatigued
A10 Perceived problems with short-term memory
A11 Post exertional malaise lasting several hours
B The symptoms cause clinically significant distress or impairment in social, occupational or other
important areas of functioning
C There is evidence from the history, PE or laboratory findings that the symptoms are a
consequence of cancer or cancer therapy
D The symptoms are not primarily a consequence of comorbid psychiatric disorders such as
major depression, somatization disorder, somatoform disorder or delerium
Efficacy Assessments
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Efficacy assessments utilized to measure
fatigue and cognitive changes:
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FACIT-F = Functional Assessment of Chronic Illness
Therapy-Fatigue Subscale
CGI-S = Clinical Global Impression – Severity
CGI-I = Clinical Global Impression – Improvement
Modified SNAP = Modified Attention
Deficit/Hyperactivity Disorder (ADHD) Scale
HSCS = High Sensitivity Cognitive Screen
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6 cognitive domains of memory, language, visual-motor,
spatial, attention/concentration, and self-regulation and
planning
Predicts overall qualitative results of formal neuropsychologic
testing with 93% accuracy
Study Design
Pre-Randomization Visit 1
Baseline/Randomization Visit 2
POD
Dose Maintenance
(2-wk minimum)
Screening Period
Single-Blind Treatment Period
Placebo
Double-Blind Treatment Phase
Pre-Randomization Phase
Visit # 
Week # 
1
2
3
4
5
6
7
8
9
10
(-1)
(0)
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
Patient Demographics
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Age
52.8 yrs
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Gender
94% female
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Race
79% white, 9% African-American
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Education
50% post HS, 28% adv degree
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Work Status
63% empl., 24% unempl, 13% ret.
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Cancer type
76% breast, 14% ovarian
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FACIT-F score at baseline comparable to published surveys of
patients post- chemotherapy
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Treatment groups were well-matched for all baseline
characteristics
Change in FACIT-F (fatigue) Total Score at Each
Week
Treatment Week
0
1
2
3
4
5
6
7
8
Change from Baseline
0
-2
-4
-6
-8
-10
-12
-14
*
* p < 0.05
** p < 0.01
POD
POD LOCF
**
PLCBO
LOCF = Last observation carried forward
PLCBO LOCF
Clinical Global ImpressionImprovement
% of subjects achieving very much or much improved at each week
80
70
**
*p<0.05, **p<0.01
% subjects
60
50
40
30
20
10
0
bsln
wk1
wk2
wk3
POD
wk4
wk5
wk6
placebo
wk7
wk8
LOCF
Conclusions
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Phunonadate (POD) significantly reduced
chemotherapy–related fatigue in adult
cancer subjects compared to placebo.