Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients With Primary Gliomas
Phase: PHASE2
Conditions: Glioma, Glioblastoma
Sponsor: Wake Forest University Health Sciences

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in 
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
ClinicalTrials.gov:  NCT03868943
Principal Investigator: 
Roy E. Strowd, III MD 
Assistant Professor 
Department of Neurology 
Department of Internal Medicine 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston Salem, NC 27157 
 
Co-Investigator(s): 
Sandyha Kumar, M.D. 
Department of Neurology 
Wake Forest School of Medicine 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
 
Tiffany Cummings, PsyD 
Department of Neurology 
Wake Forest School of Medicine 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
 
Glenn J. Lesser, MD 
Department of Internal Medicine 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
Christina Cramer, M.D. 
Department of Radiation Oncology 
Wake Forest School of Medicine 
Medical Center Blvd 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
 
 
Michael Chan, M.D. 
Department of Radiation Oncology 
Wake Forest School of Medicine 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
 
 
 
 
 
 
 
Kristin Strickland, PA 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
 
Biostatistician: 
Fang-Chi Hsu, Ph.D. 
Department of Biostatistics and Data Science, 
Wake Forest Baptist Comprehensive Cancer Center 
Wake Forest School of Medicine 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
 
 
 
Research Nurse: 
 
 
Ashley Fansler, RN 
 
 
 
 
 
Brain Tumor Disease Oriented Team Research Nurse 
Wake Forest Baptist Comprehensive Cancer Center 
Wake Forest University School of Medicine 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Regulatory Contact:  
 
Cindy Miller 
Wake Forest Baptist Comprehensive Cancer Center 
Wake Forest University School of Medicine 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
 
 
Participating Institution(s):  
WFBCCC 
 
 
Version Date: 
 
 
12-27-18 
Amended: 
 
 
 
05-19-21 
 
 
Confidential
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 4 of 83 
Table of Contents 
SCHEMA .............................................................................................................................................................. 7 
1 
Background ................................................................................................................................................... 8 
2 
Hypotheses .................................................................................................................................................. 18 
3 
Objectives .................................................................................................................................................... 19 
1. 
Primary Objective(s) ........................................................................................................................... 19 
2. 
Secondary Objective(s) ....................................................................................................................... 19 
3. 
Exploratory Objective(s) ...................................................................................................................... 19 
4 
Patient Selection .......................................................................................................................................... 19 
1. 
Inclusion Criteria ................................................................................................................................. 19 
2. 
Exclusion Criteria ................................................................................................................................ 21 
3. 
Inclusion of Women and Minorities ..................................................................................................... 22 
5 
Registration Procedures .............................................................................................................................. 22 
6 
Study Outcomes and Study Measures ........................................................................................................ 23 
1. 
Primary Outcome ................................................................................................................................ 23 
2. 
Secondary Outcomes.......................................................................................................................... 23 
3. 
Exploratory Outcomes......................................................................................................................... 23 
7 
Treatment Plan ............................................................................................................................................ 23 
1. 
Overview of Treatment Plan ............................................................................................................... 23 
2. 
Study-Related Activities ...................................................................................................................... 25 
3. 
Screening ............................................................................................................................................ 26 
4. 
Pre-Treatment Baseline ...................................................................................................................... 26 
5. 
Flexible Dosing Titration ..................................................................................................................... 26 
6. 
Fixed Dose Drug Continuation ............................................................................................................ 27 
7. 
30 Day Follow Up ................................................................................................................................ 27 
8. 
Study Assessments ............................................................................................................................ 27 
9. 
Treatment Administration .................................................................................................................... 30 
1. 
Definition of Dose-Limiting Toxicity (DLT) ........................................................................................... 30 
2. 
Other Agent(s) .................................................................................................................................... 32 
3. 
Other Modality(ies) or Procedures ...................................................................................................... 32 
10. 
General Concomitant Medication and Supportive Care Guidelines .................................................... 32 
11. 
Duration of Therapy ............................................................................................................................ 33 
12. 
Duration of Follow Up ......................................................................................................................... 33 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 5 of 83 
13. 
Determination of Evaluable Patients ................................................................................................... 33 
14. 
Criteria for Removal from Study .......................................................................................................... 33 
8 
Dosing Delays/Dose Modifications .............................................................................................................. 33 
9 
Measurement of Effect ................................................................................................................................ 34 
10 
Adverse Events List and Reporting Requirements ................................................................................. 34 
1. 
Adverse Event List for solriamfetol...................................................................................................... 34 
2. 
DSMC SAE Reporting Requirements ................................................................................................. 36 
3. 
WFUHS IRB AE Reporting Requirements .......................................................................................... 36 
4. 
Sponsor Reporting Requirements ....................................................................................................... 37 
11 
Pharmaceutical Information .................................................................................................................... 37 
1. 
Pharmaceutical Accountability ............................................................................................................ 37 
2. 
Solriamfetol 44 ...................................................................................................................................... 37 
12 
Data Management .................................................................................................................................. 38 
13 
Statistical Considerations ........................................................................................................................ 39 
1. 
Analysis of Primary Objective ............................................................................................................. 39 
2. 
Analysis of Secondary Objective ......................................................................................................... 39 
3. 
Analysis of Exploratory Objective ........................................................................................................ 39 
4. 
Power and Sample Size ...................................................................................................................... 39 
5. 
Estimated Accrual Rate....................................................................................................................... 40 
6. 
Estimated Study Length ...................................................................................................................... 41 
7. 
Interim Analysis Plan .......................................................................................................................... 41 
References ......................................................................................................................................................... 42 
Appendix A – Eligibility Checklist ........................................................................................................................ 46 
Appendix B – Protocol Registration Form ........................................................................................................... 49 
Appendix C - Race & Ethnicity Verification Form ............................................................................................... 50 
Appendix D – Mandatory DSMC SAE Reporting Guidelines .............................................................................. 51 
Appendix E – Adverse Event Log ....................................................................................................................... 58 
Appendix F - Patient Drug Diary ......................................................................................................................... 59 
Appendix G – Fixed Dosing Patient Drug Diary .................................................................................................. 60 
Appendix H – Epworth Sleepiness Scale (ESS) ................................................................................................. 62 
Appendix I – Pittsburgh Sleep Quality Index (PSQI) .......................................................................................... 63 
Appendix J – Brief Fatigue Inventory (BFI) ......................................................................................................... 65 
Appendix K – Cancer Fatigue Scale (CFS) ........................................................................................................ 66 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 6 of 83 
Appendix L – Beck Depression Inventory ........................................................................................................... 67 
Appendix N – FACT Br (Version 4) ..................................................................................................................... 71 
Appendix O – Concurrent Medications Form ...................................................................................................... 76 
Appendix P – Off-Study Form ............................................................................................................................. 77 
Appendix Q – MR Imaging Record ..................................................................................................................... 79 
Appendix R – Sleep Diary and Actigraphy Record ............................................................................................. 80 
Appendix S – Glioma History .............................................................................................................................. 81 
Appendix T – Telephone Script .......................................................................................................................... 83 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 7 of 83 
SCHEMA 
 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 8 of 83 
1 
Background 
 
Patients with primary brain tumors suffer from a unique constellation of symptoms that result from the 
tumor and its treatment, including (1) the infiltration of tumor into brain, (2) the effects of directing 
treatment toward the tumor (e.g. perioperative deficits, cerebral edema, radiation necrosis), and (3) 
short and long-term toxicities from treating the brain with radiation therapy (e.g. cognitive dysfunction, 
hormonal deficiences, etc), and chemotherapy (e.g. cognitive dysfunction, fatigue, etc). While the 
burden of symptoms is unique to each patient, several symptom clusters predominate including sleep-
wake disturbances. 
 
 
1. 
Sleep-wake Disturbance is Common in Brain Tumor Patients 
 
Cancer-associated sleep-wake disturbances are common and reportedly affect up to 50-60% of 
cancer patients.1–3 Sleep disruption occurs across the continuum of cancer care affecting 48% 
at the time of diagnosis,4 36% during cycle 1 of chemotherapy,5 and 65% of cancer survivors.6 
The majority of prior studies have focused on breast and lung solid tumor patients, often 
excluding those with brain tumors. 
 
A small number of studies have explored 
sleep disturbances in patients with 
primary brain tumors. A recent 
systematic review identified 11 primary 
research studies that evaluated sleep 
dysfunction in brain tumor patients. 
Many of these studies were retrospective 
reviews and often focused primarily on 
fatigue with sleep being a secondary or 
exploratory outcome. In these studies, 
sleep-wake disturbance was one of the 5 
most common symptoms reported by 
brain tumor patients.7 Sleep 
disturbances clustered with other 
symptoms including fatigue, depression, 
and cognitive impairment.8 Such data 
support what clinicians have long 
appreciated in caring for these patients, that sleep-disturbances exist and co-occur with fatigue 
and neurocognitive dysfunction. This so-called sleep-fatigue-neurocognitive symptom cluster 
(Figure 1) results in significant quality of life impairment for patients, contributes to caregiver 
fatigue, and complicates the medical management of these patients for providers. 
 
Sleep-disturbance is central to the symptom cluster displayed in Figure 1. Sleep disturbances 
are known to contribute to daytime fatigue and reduce daytime energy. Sleep-disturbances have 
been shown to contribute to poorer performance on neuro-cognitive batteries, reduce speed of 
processing, impair reflex times, and impair daily functioning.7 As a result, interventions which 
target sleep dysfunction and address the symptoms observed within this cluster are extremely 
attractive and could substantially impact the lives of glioma patients. 
 
2. 
Potential Causes of Sleep-wake Disturbance in Brain Tumor Patients 
Primary brain tumor patients lie at a unique intersection between cancer-associated and 
neurological illness-related sleep disturbance where both the location of the tumor and its 
Figure 1: Schematic Flow Diagram of the Sleep-Fatigue-
Neurocognitive Symptom Cluster 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 9 of 83 
oncologic treatment impact sleep-wake homeostasis. Cranial irradiation is one of the most 
significant factors associated with hypersomnia and sleep dysfunction.9–11 However, numerous 
additional factors contribute to sleep disturbance including the frequent use of corticosteroids,12 
disruption of hypothalamic-pituitary axis signaling,12 dysfunction in melatonin and hypocretin 
production,13,14 timing of chemotherapy,15–17 reduced physical activity due to neurological 
deficits,18 anxiety and depression.19–21 
 
Neuroinflammation may be a common mechanism underlying each of these clinical 
observations. Preclinical models indicate that elevated levels of circulating cytokines (e.g. IL-6, 
TGF-alpha, and IFN-gamma) contribute to alterations in norepinephrine, serotonin, dopamine, 
and melatonin signaling in brain tumor models.22,23 These inflammatory mediators act on the 
brain via two pathways: (1) increased cytokine activity alters neurally-mediated signaling 
through the vagus nerve, and (2) activation of humoral immune pathways increase the 
expression of immune mediators (e.g. prostaglandins, COX-2, etc) at the blood-brain interface 
and promote a proinflammatory state in the central nervous system.24–26 The link between sleep 
and neuroinflammation has gained particular attention recently. Studies aging, dementia, and 
Alzheimer’s disease have suggested that poorer sleep may be associated with increased brain 
inflammation which if sustained chronically could contribute to an increased risk of subsequent 
dementia and neurocognitive deficits.27–32 
 
In brain tumor patients, variations in melatonin production may be particularly important. 
Melatonin secretion functions as a regulator of the central molecular clock. Melatonin is 
synthesized in the pineal gland in response to inputs from the suprachiasmatic nucleus. Once 
synthesized, melatonin is released into both the cerebrospinal fluid and systemic circulation 
where it has pleiotropic actions on numerous organ-systems including the monoaminergic 
neurotransmitter system primarily through two receptor types, named MT1 and MT2.33 As a 
result, melatonin serves as a key intermediary in the connection between sleep regulation and 
serotonin, dopamine, and norepinephrine signaling.33 In fact, in addition to its actions on 
neurotransmitter signaling, melatonin has been shown to effect cerebral cytokine production, 
contribute to pro-inflammatory TNF-alpha secretion, and perpetuate the sleep-cognition-fatigue 
cluster in patients undergoing radiation therapy.34–38 
 
These data support developing and testing pharmacologic agents with broad actions on 
neurotransmitter systems including the dopaminergic and noradrenergic systems to target the 
mechanistic drivers of sleep-disturbances in patients with primary brain tumors. 
 
 
3. 
Prior Clinical Studies of Agents for Treating Sleep-Wake Disturbance in Gliomas 
Prior intervention studies seeking to improve the sleep-fatigue symptom cluster in patients with 
primary brain tumors have not resulted in changes to clinical practice. 
 
Modafinil was not better than placebo in improving patient symptoms. In fact 32% of patients 
dropped out of the study mostly due to treatment-related side effects.8 In another study 
randomizing patients to either modafinil or methylphenidate, both agents were found to improve 
neuro-cognition but neither agent benefited patient reported increase in daytime sleepiness.8 
The majority of intervention studies have focused primarily on fatigue and neurocognitive 
outcomes (Table 1).8,39–43 When included sleep has not been a primary outcome. Measures 
used to assess sleep dysfunction have varied and included the Epworth Sleepiness Scale 
(ESS), the brief sleep disturbance scale (BSDS), and in some studies, sleep has not been 
assessed at all. These data underscore the importance of exploring novel agents with new 
mechanisms that focus on sleep as the primary outcome. 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 10 of 83 
 
 
 
Table 1: Clinical Studies of Agents for Treating Sleep-Fatigue-Neuro-cognition Symptom Cluster 
in Glioma Patients 
 
Study / 
Author 
Agent(s) 
Primary Outcomes 
Measures 
Key Study Finding 
Gehring et al.41 
Methylphenidate (2 
doses) vs Modafinil 
Cognitive function (cognitive 
battery), sleep (BSDS), mood, 
QOL (FACT-Br) 
Similar improvements in 
cognition in both treatment 
arms, no change in sleep 
Boele et al.8 
Modafinil vs 
placebo 
Fatigue (CIS), cognitive function 
(SF-Cog), mood (CES-D), QOL 
(SF-36) 
No difference in fatigue, 
cognition, and mood between 
modafinil and placebo 
Berk et al.40 
Melatonin vs 
placebo 
Survival 
No difference in survival 
between melatonin and 
placebo 
Lee et al.42 
Armodafinil vs 
placebo 
Radiation-induced fatigue (BFI, 
FACIT-F, CFS) 
No difference in fatigue 
between armodafinil and 
placebo 
Page et al.43 
Armodafinil vs 
placebo 
Radiation-induced fatigue (BFI, 
FACIT-F) 
No difference in fatigue 
between armodafinil and 
placebo, 
Caption: Quality of life, QOL. Brief fatigue inventory, BFI. Functional Assessment of Chronic Illness – 
Fatigue subscale, FACIT-F. Cancer-fatigue scale, CFS. Checklist individual strength, CIS. Center for 
epidemiologic studies depression scale, CES-D. Medical outcomes study short-form health survey, SF-36. 
Medical outcomes study short-form subjective cognitive functioning scale, SF-Cog. Brief sleep disturbance 
scale, BSDS. FACT-brain module, FACT-Br. 
 
 
4. 
Preliminary Data on Sleep-Wake Disturbance in Gliomas and Rationale for Solriamfetol 
 
At the American 
Academy of 
Neurology Annual 
Meeting, we recently 
presented the results 
of a pilot cross-
sectional study 
evaluating the 
prevalence, risk 
factors, associated 
symptoms, and 
quality of life impact 
of self-reported sleep-
wake disturbances in 
a cohort of patients with primary gliomas (Figure 2). 
 
Figure 2: Study design from the prior cross-sectional study of sleep disorders in brain 
tumors patients 
Figure 3: Prevalence of patient-reported excessive daytime sleepiness 
by Epworth Sleepiness Scale (ESS) scores 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 11 of 83 
A prospective cohort of 50 
brain tumor patients was 
recruited to complete a one-
time survey-based assessment 
of self-reported sleep 
disturbance using the Epworth 
Sleepiness Scale (ESS), 
Pittsburgh Sleep Quality Index 
(PSQI), a previously validated 
sleep hygiene and sleep habits 
questionnaire, as well as 
clinical and treatment 
characteristics, and quality of life (e.g. EQ-5D). In this study, excessive daytime sleepiness 
(EDS, ESS>10) was reported in 46% of brain tumor patients (Figure 3). Patient-reported ESS 
was generally correlated with caregiver observed ESS for the patient (r=0.56, p=0.005), though 
important differences were present at the extremes of patient ESS. Abnormally low ESS 
(ESS<5) was observed in 16% of patients, meaning that a normal ESS score was only 
observed in 36% of the cohort. Self-reported excessive daytime sleepiness (ESS>10) was 
significantly more common in patients who had ever undergone chemotherapy (42% vs 22%, 
p<0.008) but not radiation therapy (p=0.30) or by tumor grade (p=0.25). Fifty-two percent of 
patients on active corticosteroids had ESS>10 compared to only 28% of those not taking 
corticosteroids (p=0.17). Chemotherapy treatment was associated with nighttime awakenings 
(p=0.04) while corticosteroid use was associated with lower daytime energy (p=0.04). EDS was 
also associated with poorer health-related QOL including reduced mobility (p<0.03) and 
impaired daily activities (p<0.02). These preliminary data support that: 
 
1. Sleep-wake disturbances in the form of patient-reported excessive daytime sleepiness are 
common in brain tumor patients 
2. That patient ESS can be used to evaluate self-reported sleep dysfunction given the 
correlation with caregiver observation, and 
3. Indicate that a sufficient population can be identified by ESS>10 for recruitment into an 
intervention study (roughly 50% of primary glioma patients) 
 
 
5. 
Clinical Data on Solriamfetol for treating Excessive Daytime Sleepiness (EDS) 
Solriamfetol (JZP-110) is a late stage investigational wakefulness-promoting agent that has been 
studied for the treatment of excessive daytime sleepiness (EDS). Prior studies have focused on 
adult patients with narcolepsy or obstructive sleep apnea. The mechanism of action of 
solriamfetol though not fully determined includes low potency dopamine and norepinephrine 
reuptake inhibition.44 Solriamfetol’s actions appear to be distinct from modafinil and traditional 
stimulants. 
 
To date, solriamfetol has been found to be safe and well tolerated. Efficacy and safety have been 
demonstrated in several phase 2 and phase 3 studies. FDA approval is anticipated for treating 
EDS in patients with narcolepsy and obstructive sleep apnea. 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 12 of 83 
1.5.1 
Clinical Trials of Solriamfetol in Narcolepsy 
 
To date, a Phase 2a, Phase 2b, and Phase 3 clinical trial has been conducted in patients with 
narcolepsy.45–47 
 
Randomized Placebo-Controlled Phase 2a Trial in Narcolepsy47 
The Phase 2a trial was a 4-week, double-blind, placebo-controlled, multicenter, randomized, 
cross-over study. Participants were between the ages of 18 and 65 years in good general health 
with documented EDS due to narcolepsy as per the International Classification of Sleep 
Disorders, Second Edition (ICSD-2) criteria. Patients who had a baseline Epworth Sleepiness 
Scale (ESS) score greater than or equal to 10 and a baseline mean sleep latency on the 
Maintenance of Wakefulness Test (MWT) of less than or equal to 10 minutes were included. 
Exclusion criteria included customary bedtime  later than midnight; history of significant medical 
condition, behavioral or psychiatric disorder (including suicidal  ideation), or surgical history; any 
other clinically relevant medical, behavioral or psychiatric disorder other than narcolepsy 
associated with daytime sleepiness, body mass index  (BMI) greater than 34; excessive caffeine 
use (>600  mg/day  or >6 cups of coffee/day); nicotine dependence that had an effect on sleep; 
and history of alcohol or drug abuse within the past 2 years. Patients were randomized to one of 
two treatment sequences: either placebo administration for 2 weeks followed by solriamfetol for 2 
weeks, or the reverse sequence. Dosing was begun at 150 mg/day for 1 week and increased to 
300 mg/day for the second week. The primary efficacy endpoint was the change from baseline in 
average sleep latency time across the 4 MWT trials performed 2 hours apart at the end of 2 
weeks of treatment. Secondary endpoints included the change from baseline in ESS scores and 
Clinical Global Impression-Change (CGI-scores) at the end of 1 and 2 weeks of treatment. 
 
Thirty-three patients were randomized and completed both the placebo and solriamfetol periods. 
The change from baseline in average sleep latency from 4 MWT trials (primary endpoint) was 
12.7 minutes for solriamfetol and 0.9 minutes for placebo, a statistically significant difference of 11.8 
minutes  (p=0.0002). Additionally, the sleep latency on each of the 4 individual MWT trials was 
statistically significantly longer for solriamfetol than for placebo (9 to 14.6 minutes longer; p<0.001). 
On the ESS scores, there was a mean change of -5.3 for solriamfetol compared to -1.2 for 
placebo (p<0.0001) following 1 week of treatment (150 mg/day); and a mean change of -6.7 for 
solriamfetol compared to -2.4 for placebo (p=0.0002) following 2 weeks of treatment (300 mg/day 
during the second week). The CGI-C ratings demonstrated that 88%  of  patients  on  solriamfetol 
showed improvement  at 1 week of treatment compared to 27% of patients on placebo (p<0.0001); 
and at 2 weeks of treatment 76% of patients on solriamfetol and 39% of patients on placebo 
showed improvement  (p=0.0016). 
 
Adverse events occurring with  ≥5% incidence  with  solriamfetol (150  mg/day  and 300  mg/day  
combined)  included  nausea (n=4; 12%), headache (n=3;  9%), non-cardiac  chest discomfort  (n=3;  
9%), anxiety  (n=2;  6%), decreased appetite (n=2; 6%), initial insomnia (n=2; 6%), insomnia  (n=2; 
6%), and muscle tightness  (n=2; 6%). Fourteen patients (42%) experienced 1 or more adverse 
event(s) with solriamfetol (combined 150 mg/day and 300 mg/day). 
 
Randomized Placebo-Controlled Phase 2b Trial in Narcolepsy46 
The Phase 2b trial was a 12-week, double-blind, placebo-controlled, multicenter, parallel design 
study. Patients were randomized to receive either placebo (once daily) or solriamfetol (150 
mg/day during Weeks 1 through 4 and 300 mg/day during Weeks 5 through 12). The co-primary 
endpoints were the change from baseline to last assessment in average sleep latency time as 
determined by the MWT and the change from baseline to last assessment on the CGI-C. 
Change in disease status from baseline was assessed at 1, 2, 4, 6, 8, and 12 weeks using the 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 13 of 83 
CGI-C and the Patient Global Impression of Change (PGI-C) scales.  Secondary endpoints 
included the change from baseline in  ESS score at Week 4 and Week 12. 
 
Ninety-three patients were randomized in the study, of whom 49 patients were randomized to 
placebo and 44 patients to solriamfetol. The 2 treatment groups were similar in demographic and 
clinical characteristics. The sample was 64.5% female, 74.2% white with a mean (standard 
deviation [SD]) age of 38.7 (12.1) years and a baseline mean (SD) ESS score of 17.3 (3.3). At 
Week 4, there were statistically significant differences in the change from baseline with solriamfetol 
relative to placebo in average sleep latency on the MWT (increase of 9.5 minutes for solriamfetol 
vs. 1.4 minutes for placebo; p<0.0001); CGI-C ratings (80% improved for solriamfetol vs. 51% 
improved  for placebo; p=0.0066); and ESS scores (decrease of 5.6 points for solriamfetol vs. 2.4 
points for placebo; p=0.0038). At Week 12, treatment with solriamfetol resulted in statistically   
significantly greater changes from baseline compared with placebo in average sleep latency on 
MWT (12.8 minutes for solriamfetol vs. 2.1 minutes for placebo; p<0.0001); ESS scores (8.5 points 
for solriamfetol vs. 2.5 points  for placebo; p<0.0001); and proportion of patients with improvement  
on  the CGI-C (86% for solriamfetol vs. 38% for placebo; p<0.0001).  Also at Week 12, statistically 
significantly more patients improved on the PGI-C with solriamfetol compared with placebo (93.0% 
for solriamfetol vs. 38.3% for placebo; p<0.0001). The percentage of PGI-C scores that matched 
the CGI-C scores was 74.4%, with a strong and significant correlation between the scores 
(Spearman r = 0.868; p<0.0001). The 10 patients who reported they were “very much improved” 
on the PGI-C at Week 12 had a mean reduction of 76.7% on the ESS, and the 33 patients who 
reported they were “much improved” on the PGI-C at Week 12 had a mean decrease in ESS 
score of 49.1%. Three patients (6.8%) randomized to solriamfetol discontinued due to adverse 
events. The most common adverse events occurring in patients in the solriamfetol and placebo 
groups, respectively, were headache (16%, 10%), nausea (14%, 6%), diarrhea (11%, 6%), 
insomnia (14%, 2%), decreased appetite (14%, 0%), and anxiety (11%, 0%). Two serious adverse 
events (conversion disorder and acute cholecystitis) occurred in the solriamfetol group; these 
adverse events were considered probably unrelated to the study drug by the investigators. 
 
Randomized Placebo-Controlled Phase 3 Study in Narcolepsy45 
The Phase 3 study was a 12-week, double-blind, randomized, placebo-controlled, parallel group 
study evaluating the safety and efficacy of solriamfetol for the treatment of excessive sleepiness 
and impaired wakefulness in patients with narcolepsy. Patients were randomized 1:1:1:1 to 
receive daily placebo or solriamfetol 75 mg, 150 mg, or 300 mg, and randomization was 
stratified by the presence or absence of cataplexy. The co-primary study endpoints were the 
change from baseline to Week 12 in mean sleep latency on the MWT and the change from 
baseline to Week 12 in the ESS score. The key secondary endpoint was the percentage of 
patients who reported improvement on the Patient Global Impression of Change (PGI-C) at 
week 12. Evaluation of safety included adverse events (AEs), laboratory tests, and vital signs. 
 
Of the 239 patients randomized, 236 received at least one dose of study drug and were 
included in the safety population.2 The modified intention to treat (mITT) population consisted of 
231 patients, of whom 58 patients were randomized to placebo, 59 patients to solriamfetol 75 
mg, 55 patients to solriamfetol 150 mg, and 59 patients to solriamfetol 300 mg. A total of 195 
patients completed the study (52 patients in the placebo group, 49 in the solriamfetol 75 mg 
group, 51 in the solriamfetol 150 mg group, and 43 in the solriamfetol 300 mg group). In the 
mITT population (n=231), the discontinuation rate was highest in the solriamfetol 300 mg group 
(27.1%) compared with the placebo (10.3%), solriamfetol 75 mg (16.9%), and solriamfetol 150 
mg (7.3%) groups. The most common reasons for discontinuation in the solriamfetol 300 mg 
group were lack of efficacy (10.2%, n=6) and adverse events (8.5%, n=5). 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
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Demographics and clinical characteristics were similar among treatment groups at baseline, and 
participants were mostly white, female, age in the mid-thirties, and with a BMI over 25 kg/m2. 
Patients had excessive sleepiness at baseline as indicated by ESS scores and MWT mean 
sleep latency times. The study met the co-primary endpoints of change from baseline in MWT 
and ESS and the key secondary endpoint of percentage of patients with improvement on PGI-C 
at solriamfetol-150 mg and 300 mg at week 12 (Table 2). Statistical significance was not 
achieved for solriamfetol 75 mg on the MWT. 
 
 
Table 2. Hierarchical Testing of Co-Primary and Key Secondary Efficacy Endpoints in the 
Modified Intent-to-Treat Population (Week 12) 
 
Endpoint 
Solriamfetol 
300 mg 
Solriamfetol 
150 mg 
Solriamfetol 
75 mg 
Maintenance of Wakefulness Test 
<0.0001 
<0.0001 
0.1595 
Epworth Sleepiness Scale 
<0.0001 
<0.0001 
0.0211 
Patient Global Impression of Change 
<0.0001 
<0.0001 
0.0023* 
Table displays p-values. 
*Nominal p-value since below the hierarchical break. 
 
Solriamfetol 150 mg and Solriamfetol 300 mg significantly increased MWT mean sleep latency 
relative to placebo at week 12 in the mITT population. Statistically significant effects were seen 
as early as week 1 for Solriamfetol 150 mg and 300 mg, and continued throughout the 12 weeks 
of the study. The effects on the MWT appeared to be dose-dependent over the 12 weeks of the 
study. At Week 12, Solriamfetol at all doses significantly reduced ESS scores from baseline 
relative to placebo in the mITT population (Table 3). Statistically significant effects were 
observed for Solriamfetol 150 mg and 300 mg as early as week 1. Effects on the ESS were 
dose-dependent over the 12 weeks of the study. 
 
Table 3. Mean Change from Baseline on the Epworth Sleepiness Scale Score 
Group 
Least Squares Mean Change from Baseline on ESS Score 
Week 1 
Week 4 
Week 8 
Week 12 
Placebo (n=58) 
–2.7 
–2.2 
–2.1 
–1.6 
Solriamfetol 75 mg (n=59) 
–3.2 
–3.3 
–3.4 
–3.8† 
Solriamfetol 150 mg (n=55) 
–5.5† 
–5.6* 
–5.2† 
–5.4* 
Solriamfetol 300 mg (n=59) 
–6.7* 
–5.6* 
–6.4* 
–6.4* 
†p<0.05 vs. placebo. 
*p<0.0001 vs. placebo 
The most common (≥5%) adverse events (AEs) in all solriamfetol groups were headache, 
nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety. In general, the incidence 
of the most common AEs was dose-dependent. One patient in the solriamfetol 150 mg group 
had 2 serious AEs consisting of non-cardiac chest pain and anxiety that were deemed not to be 
related to the study drug by the investigator. This patient continued in the study. 
Discontinuations due to AEs were greater in the solriamfetol 150 mg and 300 mg groups than in 
the placebo group. 
 

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1.5.2 Clinical Trials in Obstructive Sleep Apnea 
Solriamfetol has also been studied in clinical trials in patients with EDS from obstructive sleep 
apnea (OSA).48 
 
Randomized, Placebo-Controlled, Double-Blind, 12-Week Multicenter Study in OSA 
A 12-week, double-blind, randomized, placebo-controlled parallel design study evaluated the 
efficacy and safety of solriamfetol for the treatment of excessive sleepiness in adult patients with 
OSA. Patients were randomized in a 1:1:2:2:2 ratio to solriamfetol 37.5 mg, 75 mg, 150 mg, 300 
mg, or placebo and stratified by adherence to OSA treatment. The co-primary efficacy endpoints 
were the change from baseline to week 12 on the MWT and the ESS. The study was completed 
by a total of 404 patients (101, 49, 54, 106, and 94 patients in the placebo, solriamfetol 37.5 mg, 
solriamfetol 75 mg, solriamfetol 150 mg, and solriamfetol 300 mg groups, respectively). The 
overall number of discontinuations was highest in the solriamfetol 300 mg group (n=21) relative 
to the numbers of patients discontinued in the placebo group (n=13), solriamfetol 37.5 mg group 
(n=7), solriamfetol 75 mg group (n=4), and solriamfetol 150 mg group (n=10). The baseline 
characteristics were similar among the treatment groups. All doses of solriamfetol met the co-
primary endpoints. Effects were dose-dependent and the greatest effect was seen at the 
solriamfetol 150 mg and 300 mg doses. 
 
Solriamfetol at all doses significantly increased the mean MWT sleep latency at weeks 4 and 
12, and at the 75 mg, 150 mg, and 300 mg doses as early as week 1. At the 150 mg and 300 
mg doses, solriamfetol increased the mean MWT sleep latency by over 10 minutes at all time 
points. Increases in mean MWT sleep latency were dose-dependent across the duration of the 
study solriamfetol significantly decreased ESS scores at all doses at week 12 and as early as 
week 1 (Table 4). Decreases in ESS score were dose-dependent across the study duration. At 
week 12, solriamfetol at the 150 mg and 300 mg doses decreased mean ESS scores by more 
than 7 points. 
 
 
 
 

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Table 4. Mean Change from Baseline on the Epworth Sleepiness Scale (ESS) Score at Weeks 
1, 4, 8, and 12 
 
Group 
Least Squares Mean Change from Baseline on the Epworth 
Sleepiness Scale Score 
Week 1 
Week 4 
Week 8 
Week 12 
Placebo (n=114) 
–2.6 
–2.9 
–3.8 
–3.3 
Solriamfetol 37.5 mg 
(n=56) 
–4.5† 
–4.7† 
–4.7 
–5.1† 
Solriamfetol 75 mg 
(n=58) 
–4.4† 
–4.8† 
–6.3† 
–5.0† 
Solriamfetol 150 mg 
(n=116) 
–5.5* 
–6.1* 
–6.9* 
–7.7* 
Solriamfetol 300 mg 
(n=115) 
–6.6* 
–6.6* 
–7.7* 
–7.9* 
†p<0.05 vs. placebo. 
*p<0.0001 vs. placebo 
 
 
The most common AEs (≥5%) across all doses of solriamfetol were headache, nausea, 
decreased appetite, anxiety, and nasopharyngitis. Seven serious AEs were reported in 5 
patients, which consisted of goiter (n=1) and motor vehicle accident, back pain, and sciatica 
(n=1) in the placebo group; bile duct obstruction (n=1) and streptococcal endocarditis (n=1) in 
the solriamfetol 37.5 mg group, and hyperglycemia (n=1) in the solriamfetol 150 mg group. 
There was one non-treatment related serious adverse event of coronary artery disease that 
began prior to the patient receiving solriamfetol 300 mg. Solriamfetol had a modest effect on 
blood pressure and pulse rate, with a mean increase from baseline of 1 to 4 mm Hg in systolic 
blood pressure and 1 to 3 mm Hg in diastolic blood pressure, and a mean increase from 
baseline of 2 to 5 beats per minute in pulse rate. 
 
 
Placebo-Controlled, Randomized-Withdrawal, Double-Blind, 6-Week Study in OSA 
A double-blind, placebo-controlled, randomized-withdrawal designed study evaluated the safety 
and efficacy of solriamfetol administered once daily compared with placebo for the treatment of 
excessive sleepiness in adults with OSA. The study included adult patients aged 18 to 75 years 
with OSA diagnosed according to ICSD-3 criteria, along with current or prior use of a primary 
OSA therapy including CPAP, oral appliances, or surgical intervention, a baseline ESS score of 
10 or greater, a baseline MWT mean sleep latency of less than 30 minutes on the first 4 trials of 
a 5-trial, 40-minute MWT, and a usual nightly sleep time of 6 hours or more. The study began 
with a Screening Phase lasting up to 28 days, which was followed from baseline to week 2 by a 
Titration Phase. During the Titration Phase, patients started on a once daily dose of solriamfetol 
75 mg and could be titrated up or down every 3 days up to a maximum tolerated dose of 
solriamfetol 75 mg, 150 mg, or 300 mg. A 2-week Stable Dose Phase (week 2 to week 4) 
followed, and during this phase patients continued to receive the dose they were titrated to in 
the Titration Phase for 2 weeks. During the following Double-Blind Withdrawal Phase (week 4 to 
week 6), patients who reported “much” or “very much” improvement on the PGI-C scale, and 
who had improved on the MWT and ESS at week 4 were randomized in a 1:1 ratio based on 

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primary OSA therapy compliance to receive the same current dose of solriamfetol or placebo for 
2 weeks. A Safety Follow-Up period took place for 2 weeks from week 6 to week 8. 
The co-primary efficacy endpoints were the change from week 4 to 6 on the MWT and the ESS. 
A key secondary endpoint was the percentage of patients reported as worse on the PGI-C and 
CGI-C, in which they were assessed on a 7-point scale from 1 (very much improved) to 7 (very 
much worse). Of the 402 patients who were screened, 174 patients were enrolled in the 
Titration Phase and received at least 1 dose of solriamfetol, and were included in the safety 
population. Seventeen of the 174 patients (10%) discontinued in the Titration Phase, 9 of 157 
patients (6%) discontinued in the Stable-Dose Phase, and an additional 21 patients (14%) did 
not meet the improvement criteria for randomization. In the Stable-Dose Phase there were 
14.6%, 31.8%, and 53.5% of patients in the solriamfetol 75, 150, and 300 mg groups, 
respectively. The safety population that was randomized to double-blind withdrawal included 62 
patients randomized to solriamfetol and 62 patients randomized to placebo. In the Double-Blind 
Withdrawal Phase there were 7.3%, 21.0%, and 21.8% of patients in the solriamfetol 75 mg, 150 
mg, and 300 mg groups, respectively. Two patients discontinued in the Double-Blind Phase; 
thus, the mITT population consisted of 122 patients (placebo [n=62] and solriamfetol [n=60]). 
 
Baseline values for the MWT and ESS in the mITT population were similar for those in the 
safety population. After 4 weeks of solriamfetol treatment, MWT sleep latencies increased from 
approximately 12-13 minutes to approximately 30 minutes and ESS scores decreased from 
approximately 15-16 to approximately 6 in the mITT population. During the Double-Blind 
Withdrawal Phase (from week 4 to week 6), patients who had improved on solriamfetol, and who 
continued to receive solriamfetol, remained improved on the MWT and ESS, whereas patients 
who were switched to placebo worsened on both measures. From week 4 to week 6 (Double- 
Blind Withdrawal Period), the mean MWT sleep latency went from 31.7 minutes to 29.7 minutes 
and the mean ESS score remained at 6.4 at both time points in the solriamfetol group (n=60), 
while in the placebo group (n=62) the mean MWT sleep latency values went from 29.0 minutes 
to 17.6 minutes and the mean ESS score went from 5.9 to 10.8. 
 
The mean MWT sleep latency decreased by 12.1 minutes from week 4 to week 6 in patients 
who were switched to placebo during the Double-Blind Withdrawal Phase compared with a 
change of -1.0 minute for those who remained on solriamfetol (p<0.0001). Mean ESS scores 
increased by 4.5 among patients who were switched to placebo during the Double-Blind 
Withdrawal Phase, compared with a mean decrease of 0.1 for those who stayed on solriamfetol 
(p<0.0001). 
 
More AEs occurred during the Titration Phase (48.9%) than during the Stable Dose Phase 
(10.2%). The most common AEs (≥5%) during the Titration Phase were headache, dry mouth, 
nausea, dizziness, and insomnia. 
 
6. 
Summary of Study Rationale 
In summary, sleep dysfunction is common in brain tumor patients and clusters with fatigue, 
neurocognitive dysfunction, and poor quality of life. Widespread alterations in neurotransmitters 
and cytokine signaling suggest a need to intervene with an agent that targets neurotransmitter 
signaling as opposed to daytime stimulants (e.g. methylphenidate) or circadian agents (e.g. 
melatonin). The combined dopaminergic and noradrenergic activity of solriamfetol set it apart 
from other agents (e.g. modafinil) that have been previously tested and have shown signals of 
activity on this symptom cluster. Existing therapeutic studies caution against early efficacy 
studies until safety is determined given the potential for antiepileptic drug and corticosteroid 
drug-drug interactions, sensitivity of these patients to psychoactive agents, risk of increasing 
seizure activity, and the susceptibility of this population to drug-induced cognitive dysfunction. 

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Solriamfetol is an ideal agent for testing. The drug’s combined norepinephrine and dopamine 
reuptake inhibitor properties are attractive in glioma patients who have widespread 
neurotransmitter dysfunction and a symptom cluster that includes impairments in fatigue, mood, 
and neuro-cognition.40,44  
 
Safety is an important first step and study outcome. In the published phase 2 and 3 studies of 
solriamfetol in patients with narcolepsy or obstructive sleep apnea (OSA), adverse events 
included headache (9-16%), nausea (12-14%), diarrhea (11%), decreased appetite (6-14%), 
anxiety (6-11%), chest discomfort (9%), insomnia (6%), muscle tightness (6%), nasopharyngitis 
(5-14%), and dry mouth (5-10%). Cancer patients and in particular brain tumor patients are at 
risk for some of these and other cognitive, seizure, or neurological toxicities that need to be 
explored at each of solriamfetol’s three dose levels (75 mg, 150 mg, 300 mg) prior to 
proceeding to a primary efficacy endpoint. The current trial will establish this experience. 
 
Prior studies of solriamfetol have shown early improvements in patient-reported sleep by ESS 
scores. In the current study we will also evaluate other associated symptoms of fatigue, 
neurocognition, mood, and quality of life. It is not clear that these associated symptoms will 
respond as quickly to drug therapy. In fact, according to our model of the sleep-fatigue-
neurocognitive symptom cluster (Figure 1), we suspect that improvement in fatigue, 
neurocognition, mood and quality of life are downstream of the improvement in sleep and thus, 
in this study, endpoints will be assessed after prolonged stable drug therapy. This should not 
affect the ability to assess for improvements in sleep which have been reported as early as 1 
week after solriamfetol treatment and remained stable over up to 12 weeks of continued 
treatment in the aforementioned studies. 
2 
Hypotheses 
 
1. 
Primary Hypothesis 
We hypothesize that the side effect profile of solriamfetol at doses of 75 mg daily, 150 mg daily, 
and 300 mg daily will be similar in patients with primary brain tumors to that reported in patients 
with narcolepsy and obstructive sleep apnea. 
 
Serious adverse events in patients with primary brain tumors including significant 
confusion/altered mental status, seizures, or other side effects will not be more common at the 
300 mg daily dose compared to the 150 mg and 75 mg daily doses. 
 
2. 
Secondary Hypotheses 
Secondary hypotheses include that solriamfetol treatment at maximal patient specific dosing will 
result in improvements in patient-reported excessive daytime sleepiness and sleep quality (e.g. 
ESS and PSQI), neurocognitive function (see below for neurocognitive battery), fatigue and 
mood (e.g. Brief Fatigue Inventory, Cancer Fatigue Scale, Beck Depression Inventory), and 
quality of life (FACT-Brain). 
 
3. 
Exploratory Hypotheses 
Improvements in objective measures of sleep (e.g. actigraphy, sleep diary) will be similar to 
those reported in prior studies (e.g. obstructive sleep apnea, narcolepsy). We hypothesize that 
improvements in sleep, neurocognition, fatigue, mood, and quality of life may vary by clinical 
factors such as corticosteroid use, antiepileptic use, and tumor grade by World Health 
Organization (WHO) classification. 

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3 
Objectives 
 
1. Primary Objective(s) 
1. 
To estimate the safety of solriamfetol at 75 mg daily, 150 mg daily, 300 mg daily 
as assessed by NCI CTC Adverse Events (v5.0) in patients with primary gliomas 
compared to prior studies45–47 
 
2. Secondary Objective(s) 
1. 
To estimate the effect of solriamfetol on sleep by Epworth Sleepiness Scores 
(ESS) scores in patients with primary gliomas and compare the effect to 
previously published scores in patients with OSA 
 
2. 
To estimate the effect of solriamfetol on sleep quality by Pittsburgh Sleep Quality 
Index scores 
 
3. 
To estimate the effect of solriamfetol on neurocognitive function based on a 
disease-specific neurocognitive battery (see neurocognitive battery below) 
 
4. 
To estimate the effect of solriamfetol on patient-reported fatigue (Brief Fatigue 
Inventory, Cancer Fatigue Scale) & mood (Beck’s Depression Inventory) 
 
5. 
To estimate the effect of solriamfetol on patient-reported QOL (FACT-Br) 
 
6. 
To estimate the effect of solriamfetol on objective sleep-wake times by actigraphy 
and sleep diary (pre- vs post-treatment) 
 
3. Exploratory Objective(s) 
1. 
To explore a biologic gradient effect of increasing doses of solriamfetol on 
actigraphy 
 
2. 
To explore differences in clinical activity of solriamfetol by corticosteroid use, 
antiepileptic use, and tumor grade 
4 
Patient Selection 
 
Inclusion and exclusion criteria represent standard criteria for other sleep studies in this population (e.g. 
inclusion criteria) and standard exclusions for prior studies of this agent (e.g. exclusion criteria).8,39,40 
1. Inclusion Criteria  
1. WHO Grade 2-4 infiltrating glioma by histologic confirmation 
 
• 
Where appropriate results from clinically available testing of isocitrate 
dehydrogenase (IDH) gene mutation status (for all gliomas), 
chromosome 1p and 19q deletion status (for suspected 
oligodendrogliomas), and MGMT gene promoter methylation status 
(for malignant gliomas) must be available in the patient’s chart. 

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• 
These studies are standard of care molecular studies that are performed 
as a part of routine clinical practice and allow for integrated molecular 
subtyping of primary glial tumors. 
 
2. Epworth Sleepiness Scale (ESS) score >10 within 21 days of enrollment 
 
3. Clinical and/or radiographic evidence of stable disease within 21 days of enrollment 
 
4. Patients must have completed concurrent chemoradiation with recovery of all pre-existing 
toxicity to CTCAE Grade >1 
 
• 
Patient who are anticipated to undergo surgery and/or radiation therapy 
for management of their tumor during the duration of study treatment 
are NOT eligible. 
 
• 
Patients who are anticipated to undergo adjuvant chemotherapy are 
eligible as long as there is no evidence of tumor progression by 
clinical exam and/or imaging within 21 days of enrollment (see 4.1.2). 
This determination should be made by clinical documentation and if 
there is question discussed with the Study Chair. Adjuvant 
chemotherapy is not an exclusion. 
 
• 
Patients who are currently undergoing chemotherapy, targeted therapy, 
immunotherapy, or salvage treatment and have stable disease by 
imaging are eligible and can continue the current anti-cancer therapy. 
Patients who will require a new anti-cancer treatment or are 
anticipated to change anti-cancer treatments are not eligible. 
 
5. Age > 18 years 
 
6. Karnofsky performance status ≥ 60% 
 
7. Life expectancy of greater than 4 months 
 
8. Patients must have normal organ and marrow function as defined below: 
 
- leukocytes 
>3,000/mcL 
- absolute neutrophil count 
>1,500/mcL 
- platelets 
>100,000/mcL 
- total bilirubin 
1.5 X institutional upper limits of normal 
- AST(SGOT)/ALT(SGPT) 
<2.5 X institutional upper limit of normal 
- creatinine 
within normal institutional limits 
 
OR  
 
- creatinine clearance 
>50 mL/min/1.73 m2 for patients with creatinine levels 
above institutional normal. 
 
9. The effects of solriamfetol on the developing human fetus are unknown. For this reason 
women of child-bearing potential and men must agree to use adequate contraception 
(hormonal or barrier method of birth control; abstinence) prior to study entry and for the 
duration of study participation. Should a woman become pregnant or suspect she is 

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pregnant while participating in this study, she should inform her treating physician 
immediately 
 
10. Ability to understand and the willingness to sign an IRB-approved informed consent 
document (either directly or via a legally authorized representative) 
2. Exclusion Criteria  
1. Receiving active radiation therapy (including patients who are within 28 days of completing 
radiation therapy) 
 
2. Anticipated to undergo radiation therapy or require neurosurgical intervention during the 
period of active treatment (i.e. within the next 4 months) 
 
3. Contraindication to solriamfetol based on drug-drug interactions or concurrent systemic 
illness that precludes drug treatment 
 
4. Patients who have not recovered to <CTCAE grade 2 toxicities related to prior or current 
therapy are ineligible. 
 
• 
Exception for laboratory-based or other adverse event that is stable and 
not anticipated to interfere with study related treatment must be 
reviewed and approved by the Study Chair. 
 
5. Customary bedtime later than midnight 
 
6. Known and/or documented history of obstructive sleep apnea (OSA) 
7. Uncontrolled behavioral or psychiatric disorder (including suicidal ideation) 
 
8. Current excessive caffeine use (>600 mg/day or >6 cups of coffee/day) 
 
9. Current or prior history of alcohol or drug abuse within the last 2 years as assessed by the 
treating clinician 
 
10. Nicotine dependence that is currently interfering with sleep based on assessment by the 
treating clinician 
 
11. Concurrent use of selective serotonin or norepinephrine reuptake inhibitors (e.g. SSRI, 
SNRI) within 14 days of study enrollment 
 
• 
Patients who are currently taking these agents may be tapered at the 
direction of the treating physician prior to study enrollment. 
 
• 
Patients taking other medications such as narcotics, benzodiazepines, 
antipsychotics, antiepileptics, corticosteroids, or over-the-counter 
sleep aids can be enrolled. It is recommended that the doses of these 
medications remain the same throughout the portion of active study 
treatment unless there is a medical indication for dose adjustment 
which will be determined by the treating physician (see Section 7.10). 
 
12. History of allergic reactions attributed to compounds of similar chemical or biologic 
composition to solriamfetol 

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13. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, 
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or 
psychiatric illness/social situations that would limit compliance with study requirements 
 
14. Pregnant women are excluded from this study because there is an unknown but potential 
risk for adverse events in nursing infants secondary to treatment of the mother with –
solriamfetol, breastfeeding should be discontinued if the mother is treated with 
solriamfetol 
3. Inclusion of Women and Minorities 
Men and women of all races and ethnicities who meet the above-described eligibility criteria are 
eligible to participate in this study.  
5 
Registration Procedures 
All patients entered on any WFBCCC trial, whether treatment, companion, or cancer control trial, must 
be linked to the study in EPIC within 24 hours of Informed Consent. Patients must be registered prior to 
the initiation of treatment.   
You must perform the following steps in order to ensure prompt registration of your patient: 
 
1. Complete the Eligibility Checklist (Appendix A) 
2. Complete the Protocol Registration Form (Appendix B) 
3. Alert the Cancer Center registrar by phone, and then send the signed Informed Consent Form, 
Eligibility Checklist and Protocol Registration Form to the registrar, either by fax or e-mail. 
 
Contact Information: 
Protocol Registrar PHONE 
 
Protocol Registrar FAX 
 
Protocol Registrar E-MAIL 
 
            
*Protocol Registration is open from 8:30 AM - 4:00 PM, Monday-Friday. 
 
4. Fax/e-mail ALL eligibility source documents with registration. Patients will not be registered without 
all required supporting documents. 
Note: If labs were performed at an outside institution, provide a printout of the results. Ensure that the 
most recent lab values are sent. 
 
To complete the registration process, the Registrar will:   
 
• 
assign a patient study number 
• 
register the patient on the study 
 
 

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6 
Study Outcomes and Study Measures 
 
This is a single-arm, open label, non-randomized safety study in patients with glioma with each patient 
undergoing both a dose-escalation and fixed drug continuation phase of the study. The primary 
objective is to compare the safety of oral solriamfetol at doses of 75 mg daily, 150 mg daily and 300 mg 
daily. Secondary objectives include determining the effect of solriamfetol on patient-reported sleep, 
neurocognition, fatigue, mood, quality of life, and objective measures of sleep. 
1. Primary Outcome 
1. 
The primary outcome measure will be adverse events as assessed by the NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 
2. Secondary Outcomes 
1. 
The effect of solriamfetol on patient-reported sleep will be assessed by Epworth 
Sleepiness Scale (ESS) scores 
 
2. 
The effect of solriamfetol on patient-reported sleep quality will be assessed by 
Pittsburgh Sleep Quality Index (PSQI) scores. 
 
3. 
The effect of solriamfetol on neurocognitive function will be assessed by a 
disease-specific Neurocognitive Battery (Section 7.8). 
 
4. 
The effect of solriamfetol on patient-reported associated symptoms will be 
assessed by the Brief Fatigue Inventory (BFI) and the Cancer Fatigue Scale 
(CFS) for determining the effect on fatigue and by the Beck’s Depression 
Inventory (BDI) for determining the effect on depression and mood. 
 
5. 
The effect of solriamfetol on patient-reported QOL will be assessed by the FACT-
Brain module (FACT-Br). 
 
6. 
The effect of solriamfetol on changes in objective sleep-wake times will be 
assessed by actigraphy and patient-reported sleep diary (see Section 7.8). 
3. Exploratory Outcomes 
1. 
Actigraphy in relation to increasing doses of solriamfetol. 
 
2. 
Differences in clinical activity of solriamfetol by treatment factors will be assessed 
by recording corticosteroid dose at baseline, antiepileptic use (presence/absence 
of prescribed antiepileptic and dose at baseline), and tumor grade by World 
Health Organization (WHO) criteria. 
7 
Treatment Plan 
1. Overview of Treatment Plan 
This is a single-arm, open label, two-part safety study of solriamfetol in patients with WHO 
grade 2-4 gliomas. Patients with stable disease by clinical examination and neuroimaging who 
have an ESS>10 and meet all inclusion/exclusion criteria will be recruited and enrolled. First, all 
patients will receive solriamfetol at escalating doses. Second, all patients will complete a fixed 
dose drug continuation treatment at the patient-specific maximum tolerated dose. 
The study will occur in 3 phases: 

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1. 
Pre-Treatment Baseline (~1 week) 
 
2. 
Flexible Dose Titration (~3 weeks) 
 
3. 
Fixed Dose Drug Continuation (~6 weeks) 
 
Patients will initially complete a 1-week baseline actigraphy and sleep diary prior to treatment 
initiation to establish a baseline sleep pattern. 
 
Solriamfetol will be dosed by flexible dose titration starting at 75 mg daily in all patients and 
escalating after 7 days (1 week) to 150 mg daily and then after 7 days to 300 mg daily for a total 
duration of 3 weeks (flexible dose titration period). Patients who experience a dose-limiting 
toxicity will be de-escalated to the last tolerated dose level and move to the fixed dose drug 
continuation phase. Prior studies incorporating this design have used a 3-day treatment prior to 
escalation.49 For this study, 7 days has been selected to provide a sufficient period of time to 
observe both immediate and delayed toxicities that could be seen in this population. 
 
Following completion of the flexible dose titration, patients will continue solriamfetol at 300 mg 
daily or their maximally tolerated dose for a treatment duration of 6 weeks. For this period of the 
study, 8 weeks has been selected to allow for time to observe both short term improvement in 
patient-reported sleep as well as potentially more delayed changes in other study endpoints (i.e. 
fatigue, mood, neurocognition). 
 
The main study assessments will be performed at baseline prior to flexible dose titration and 
then at the end of the fixed dose drug continuation phase. This will include: (1) patient reported 
measures, (2) objective measures of sleep activity, (3) neurocognitive functioning (4) 
assessment of associated symptoms such as fatigue, mood, and (5) quality of life. Additional 
assessment of patient-reported measures will be performed after dose escalation and prior to 
the fixed dose drug continuation. Due to practice effects and other issues related to repeated 
measurement, neurocognitive data will only be collected pre- and post-treatment. 
 
Sleep diaries will be completed continuously throughout the ~10 week study. Seven-day 
actigraphy will be completed at each dose escalation and during the first and last weeks of fixed 
dose drug continuation. 
 
Additional assessments will be performed as per the standard of care. In this population, it is 
standard of care for MR Brain to be performed roughly every 8-16 weeks. Data on tumor status 
by imaging (e.g. stable disease, imaging progression, etc) will be recorded prior to study 
treatment and following study treatment to assess for tumor progression as a factor contributing 
to changes in patient-reported and clinician assessed outcome measures. 
 
Adverse events will be assessed every 7 days during flexible dose titration (via telephone) and 
at the end of the fixed dose treatment. Adverse event data will be compared to that reported in 
patients with narcolepsy.50 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
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                                              Page 25 of 83 
2. Study-Related Activities  
 
 
 
 
Pre- 
Studya,
k 
Baseline 
Visit 
V1 
Begin 
Flexible 
Dose 
Titration 
Flexible 
Dose D7  
Flexible 
Dose D14  
Fixed Dose 
Initiation 
Visit 
V2 k 
End of 
Treatment 
Visit 
V3 
30 day 
Follow 
Up Visit 
V4 k 
 
 
(D1) 
(D8+1 dy) 
(D15+1 dy) (D22+1 dy) (D29+7 dys) (D70+7 dys) 
 
Informed consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Concurrent meds 
X 
 
 
 
 
X 
X 
 
Physical exam1 
 
X 
 
 
 
X 
X 
X 
Vital signsb 
Xc 
X 
 
 
 
X 
X 
X 
CBC w/diff, platelets 
X 
 
 
 
 
X 
X 
X 
Serum chemistryd 
X 
 
 
 
 
X 
X 
X 
B-HCGe 
X 
 
 
 
 
 
 
 
Electrocardiogram (EKG) 
 
X 
 
 
 
X 
 
 
Adverse event  
evaluation 
 
 
X 
Xf 
Xf 
Xf 
X 
X 
X 
Epworth Sleepiness 
Scale (ESS) 
X 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
 
Sleep Measures: 
Sleep diary, Actigraphy h 
 
Xi 
X 
X 
X 
X 
X 
 
Pittsburgh Sleep Quality 
Index (PSQI) 
 
X 
 
 
 
X 
X 
 
Associated Symptom 
PROMs: BFI, CFS, BDI 
 
X 
 
 
 
X 
X 
 
QOL PROMs: 
FACT-Br 
 
X 
 
 
 
X 
X 
 
Neuro-cognitive Battery 
 
X 
 
 
 
 
X 
 
Standard of Care MR 
Braina 
X 
 
 
 
 
 
Xj 
 
1  Patient’s undergoing telehealth assessment at the pre-screening timepoint require virtual examination by observation only. Blood draw and 
laboratory testing can be performed locally and reviewed remotely. 
a Pre-study requirements listed in table must be completed within 21 days prior to registration. 
b Blood pressure (mmHg), heart rate (BPM) 
c Height, Weight, M2 Patients undergoing telehealth assessment can provide this information verbally using home device (e.g. scale). 
d Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, potassium, total protein, SGOT[AST], 
SGPT[ALT], sodium. 
e Serum pregnancy test (women of childbearing potential). 
f May be performed by telephone. 
g Epworth Sleepiness Scale (ESS) will be completed either in the clinic (D1, D29, D70) at each of the study visits (V1, V2, V3) or by telephone (D8, 
D15, D22) during the flexible dose escalation portion of the study. 
h 7-day sleep diary is to be completed at baseline (D1-7), continuously during dose escalation (D8-14, D15-21, D22-28), and during the first and last 
week of fixed dose drug continuation (~D29-35 and ~D63-70). Actigraphy will be collected continuously. 
i Patients may complete the baseline sleep diary and actigraphy prior to the Baseline Visit (V1) or after the Baseline Visit (V1). 
j Post-treatment MR Brain is to be performed D85 +42 days. 
k Study visits may be conducted via telehealth visit. Blood draw and EKG (when appropriate) can be performed locally and reviewed remotely. 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 26 of 83 
 
3. Screening 
Glioma patients seen at the Wake Forest Baptist Medical Center will be considered for eligibility 
at or before their scheduled visits. In general, patients may be approached at the time of routine 
outpatient visit for follow up with neuro-oncology, medical oncology, radiation oncology, and 
neurosurgery. 
 
Patients who are identified as potential study candidates will have an opportunity to hear about 
the study and complete written informed consent. Patients who sign informed consent and do 
not meet eligibility criteria will be considered screen failures, will not be evaluable for the primary 
endpoint, will not count toward the total sample size, and this enrollment will be replaced. 
 
Based on our prior cross-sectional study, we anticipate 30% of patients to be enrolled during 
adjuvant therapy (i.e. receiving oral chemotherapy), 30% during post-adjuvant surveillance (i.e. 
not receiving any prescribed antitumor therapy), and approximately 30% during post-recurrent 
disease treatment (i.e. undergoing salvage treatment with chemotherapy). This will allow for 
comparisons of toxicity, tolerability, and activity by timing during cancer care. 
 
We anticipate that approximately 20-30% of patients will be taking active corticosteroids and 
60% of patients will be prescribed an antiepileptic agent. This will allow us to explore differences 
in tolerability and activity by these important treatment parameters. 
 
Screening assessments may be completed by telehealth visit.  These will be done through 
MWH when able. If not able, Doximity will be used which is what is done clinically for these 
patients. 
 
4. Pre-Treatment Baseline 
All patients who complete written informed consent and meet eligibility criteria will be registered 
and will proceed with study treatment. For patients who complete consent at the time of a 
regularly scheduled visit they can be provided with a baseline sleep diary and actigraph device 
to complete the Pre-Treatment sleep diary and actigraphy prior to Visit 1 (V1). For patients who 
elect to take consider study enrollment and return at a later date, sleep diary and actigraphy can 
be completed after (in the first 7 days after) Visit 1 (V1).  
 
Enrolled patients will complete the pre-treatment study assessments (Section 6.7). Patients will 
be instructed to complete a 1-week pre-treatment baseline assessment with 7-day sleep diary 
that records time in bed, time awake, and estimated hours of sleep among other items 
(Appendix Q) as well as 7-day actigraphy (see Section 7.8.2). 
 
Patients will either return to clinic or receive a telephone call from the study nurse, study 
coordinator, or study team at the end of this pre-treatment baseline week (Day 7+1 day) to 
record the completion of pre-treatment baseline actigraphy and sleep diary. 
 
Baseline visit will be performed in-person. 
 
5. Flexible Dosing Titration 
Upon completion of pre-treatment baseline assessments, patients will begin flexible dosing 
titration. All patients will begin solriamfetol 75 mg p.o. once daily. The dose will be titrated every 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 27 of 83 
7 days (+1 day) to 150 mg daily and then 300 mg daily unless the patient experiences 
symptomatic dose-limiting toxicity. 
 
Adverse events will be assessed by telephone call completed on D8+1 day, D15+1 day, and 
D22+1 day. Patients will be assessed in clinic at D29+7 days. Patients who report a 
symptomatic dose-limiting toxicity will de-escalate treatment back to the highest previously 
tolerated dose and will be seen for V2. 
6. Fixed Dose Drug Continuation  
At the completion of the flexible dose titration, patients will be seen for a routine study visit (V2) 
or via telehealth visit to document adverse events at the completion of flexible dosing, review 
sleep diary and actigraphy, and complete V2 assessments. Data from this interim time point 
may be used to clarify the trajectory of improvement, decline, and no change in study 
assessments. Patients will then proceed with fixed dose treatment at 300 mg p.o. once daily or 
the maximum tolerated dose for that patient. 
 
Fixed dose drug continuation will be continued for 6 weeks. Patients will complete a sleep diary 
for the first 7 and last 7 days of fixed dose treatment; actigraphy will be collected continuously. 
At the completion of fixed dose treatment, patients will be seen for V3 study assessments 
(Section 6.7). 
7. 30 Day Follow Up  
All patients will be followed for 30 days following the completion of treatment to assess for 
delayed toxicity. Adverse events will be recorded at this 30 day follow up visit. If the patient is 
unable to return for this visit, adverse events will be recorded by telephone or telehealth visit. 
8. Study Assessments  
Assessment of sleep, neuro-cognitive function, fatigue, mood and quality of life will be assessed 
at baseline (V1) and at the end of the fixed-dose drug continuation phase of the study (V3). 
Given that patient drop out could occur during the course of the study treatment, study 
assessments that are not subject to significant practice and/or repeated measure effects will 
also be assessed after the flexible dose titration period (V2). 
 
The following assessments will be performed: 
 
1. 
Patient-reported outcome measures (PROMs) for sleep: 
 
Changes in patient-reported outcomes measures (PROMs) are pivotal to cancer control 
drug approval. 
 
The ESS is an 8-item validated instrument (min score 0 – max score 24, Appendix H) 
that is easy to implement and an accepted screening tool for symptoms of excessive 
daytime sleepiness. It has been well studied in patients with EDS and brain 
tumors.7,13,45–47,51,52 An accepted cutoff of ESS>10 has been used to indicate EDS for 
enrollment into studies evaluating therapeutic interventions.50 Prior studies have 
indicated that a 25% reduction in ESS may be useful as a threshold to identify patients 
who respond to solriamfetol treatment.53 
 
The PSQI is a 19-item validated self-report questionnaire (Appendix I) assessing sleep 
quality including subjective sleep quality, sleep latency, sleep duration, sleep efficiency, 

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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 28 of 83 
and daytime dysfunction. Prior studies demonstrate impaired sleep quality in patients 
with cancer40 and brain tumors.52 
 
The ESS and PSQI measure non-overlapping orthogonal dimensions of self-reported 
sleep-wake symptoms.52 
 
These measures will be completed prior to flexible dose titration, at the interim time point 
after flexible dose titration and before fixed dose continuation, and at end of treatment 
(see 7.2 Study-Related Activities). 
2. 
Objective measures of sleep activity: 
 
Actigraphy and sleep diaries are widely used, efficient, and affordable methods for 
measuring sleep-wake time. 
 
Actigraphy has been shown to provide accurate data that is comparable to 
polysomnography52 and is increasingly used to provide an objective measure of sleep in 
clinical trials.52 Actigraph devices are worn on the wrist and record movements that can 
be used to estimate sleep patterns using specialized computer software programs. 
Completion of actigraphy will be recorded (Appendix R). 
 
A 7-day sleep diary (Appendix R) will be provided to all patients at the time of consent 
and/or study enrollment. All sleep diaries will be collected over 7-days (i.e. 7-day sleep 
diary and 7-day actigraphy) including at pre-study baseline, throughout each dose of the 
dose escalation phase, and during the first 7-days and last 7-days of the fixed dose drug 
continuation phase of the study. Caregivers may complete sleep diaries for patients. 
Actigraphy will be collected continuously from baseline to end of treatment (see 7.2 
Study-Related Activities). 
 
3. 
Neurocognitive Battery: 
 
The table below outlines the assessment measures that will be used to evaluate 
attention, concentration, information processing speed, learning/memory, and aspects of 
higher-order executive functions. These measures were selected in accordance with 
previously established standards for cognitive assessment with brain tumor patients and 
many are used in our own multidisciplinary clinic.54–56 The protocol was modified slightly 
based on the skills most commonly identified as problematic for patients struggling with 
sleep disturbance and fatigue (attention/concentration and processing speed). 
 
All proposed measures have adequate psychometric properties and most have been 
utilized in large national and international clinical oncology trials.57,58 Alternate forms of 
the measures will be used to reduce practice effects where possible though some 
measures are less sensitive to such effects and do not have alternate forms (Digit Span, 
Letter Number Sequencing, etc.). 
 
Neuropsychological changes will be assessed on an individual basis though a reliability 
change index (RCI) can also be obtained to allow an objective measure of change in the 
measured skill. 
 
 
 

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Wake Forest Baptist Comprehensive Cancer Center 
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The following measures will be used: 
 
Test Name: 
Skill Measured: 
Alternate 
Versions: 
Time to 
Administer: 
Digit Span (DS) 
Basic rote attention 
span 
NA 
5-10 minutes 
Letter Number 
Sequencing (LNS) 
Complex working 
memory 
NA 
5-10 minutes 
Matrix Reasoning (MR) 
Visual abstract   
reasoning 
NA 
15-20 minutes 
Symbol Search (SS) 
Speeded symbol 
discrimination 
NA 
2-3 minutes 
Coding (CD) 
Clerical speed and 
accuracy 
NA 
2-3 minutes 
Controlled Oral Word 
Association Test 
(COWAT) 
Lexical and semantic 
verbal fluency and 
executive control 
2 forms 
6 minutes 
Trail Making Test Parts A 
and B (TMT A & B) 
Attention, processing 
speed, and cognitive 
set shifting 
NA 
6 minutes 
Montreal Cognitive 
Assessment (MoCA) 
Global cognitive 
functioning 
3 forms 
15 minutes 
Total 
 
 
50 – 65 minutes 
 
This battery will be completed at V1 and V3 only (see 7.2 Study-Related Activities). This 
will not be performed at the interim V2 time point due to concern with practice effects 
and limited alternate forms for many of these assessments. 
 
 
4. 
Patient-Reported Associated Symptoms: 
Sleep disturbances co-occur with symptoms of fatigue and impaired mood in patients 
with brain tumors. Furthermore, improvement in any one of these symptom domains can 
have downstream effects on the other. 
 
To assess fatigue, the Brief Fatigue Inventory (BFI) and Cancer Fatigue Scale (CFS) will 
be used (Appendix J & K). The BFI is a 9 item self-administered patient-reported 
questionnaire exploring the severity of fatigue and interference on life over the past 24 
hours.59–61 The Cancer Fatigue Scale is a 15-item self-administered patient-reported 
questionnaire exploring both overall and domain specific fatigue in cancer patients. The 
instrument explores three fatigue domains: physical effects of fatigue, cognitive effects, 
and affective issues related to cancer fatigue.62 The combination of these instruments 
provides both a unidimensional (BFI) and multidimensional (CFS) assessment of fatigue. 
The CFS domains will allow us to also explore whether there might be differential effects 
on physical fatigue or cognitive aspects of fatigue compared to the affective factors. The 
BFI and CFS have robust psychometric properties, have been validated in cancer 
patients, and were recently reviewed in the American Society of Clinical Oncology 
Patient-Reported Outcomes (PRO) Recommendations.42,43,60 
 
To assess depression, the Beck’s Depression Inventory will be used (Appendix L). The 
BDI is a commonly employed measure of depressive symptoms and has been validated 
in cancer patients.63,64 A cutoff of BDI>10 is often employed.65 

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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
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These measures will be completed at V1, V2, and V3 (see 7.2 Study-Related Activities). 
 
5. 
Quality of Life: 
The Functional Assessment of Cancer Therapy (FACT) questionnaires are commonly 
used to assess cancer-related quality of life (Appendix N). The FACT-Brain (FACT-Br) 
provides an additional set of disease-specific questions pertaining to brain neoplasms 
and is commonly used in brain tumor studies to evaluate disease-specific quality of life.65 
 
The FACT-Br will be assessed at V1, V2, V3 (see 7.2 Study-Related Activities). 
 
9. Treatment Administration 
 
Treatment will be administered on an outpatient basis. The study drug is to be taken orally once 
daily at approximately the same time each day. Each dose administered is to be recorded in the 
drug diary (Appendix F-G). 
 
Reported adverse events and potential risks are described in Section 10.0. Appropriate dose 
modifications for are described in Section 8.0. 
 
1. 
Definition of Dose-Limiting Toxicity (DLT) 
A DLT is defined as a clinically-significant AE or abnormal laboratory value assessed as 
unrelated to disease progression, intercurrent illness, or concomitant medications and 
which meets any of the criteria below. Based on the prior studies of solriamfetol in 
patients with narcolepsy and obstructive sleep apnea, treatment is anticipated to be safe 
at all doses. In the prior phase 2a study, no patient had to discontinue the study 
treatment due to a treatment-related DLT.47 In the prior phase 2b study, in patients who 
experienced an AE requiring discontinuation of solriamfetol, the AEs were not deemed to 
be related to the study medication. In the prior phase 3 study, 9 patients (9%) including 
one in the 75 mg arm, 3 in the 150 mg arm, and 5 in the 300 mg arm required 
discontinuation due to treatment related AEs.45 
 
In prior studies, common adverse events include that have not required dose medication 
include headache (9-16%), nausea (12-14%), diarrhea (11%), decreased appetite (6-
14%), anxiety (6-11%), chest discomfort (9%), insomnia (6%), muscle tightness (6%), 
nasopharyngitis (5-14%), and dry mouth (5-10%). 
 
For this study, treatment-related DLTs are defined below. Dose limiting toxicities must 
have an attribution of possible, probable, or definite to solriamfetol. For patients 
experiencing a DLT during the dose escalation period, solriamfetol will be held. If the 
patient recovers (≤ grade 1 [or tolerable grade 2 for non-hematologic toxicity] or ≤ 
baseline), a dose reduction (1 dose level reduction) is required. The patient will proceed 
with 7-days of drug treatment at the new dose level and reassessed. If there is no 
evidence of AE then the patient will proceed to the fixed dose drug continuation phase of 
the study at that dose. 
 
If there is any question or clarification required concerning a potential DLT, the treating 
clinician should contact the Study Chair to determine the patient’s DLT status. The Study 
Chair will make the final decision. 

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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 31 of 83 
 
• 
Hematological toxicities are not expected with this agent, must NOT be attributed 
to another source, and will be considered dose limiting only if any of the following 
occur and are probably or definitely attributed to solriamfetol: 
o ANC of < 500/mm3 
o Platelets < 25,000/mm3 
o Febrile neutropenia 
 
Note: Grade 3 or 4 lymphopenia will not be considered a DLT. 
• 
Central nervous system toxicities will be considered dose limiting only if any of the 
following occur: 
o ≥ Grade 2 central nervous system (CNS) ischemia will be considered a DLT 
o ≥ Grade 2 neurological toxicities that interfere with activities of daily living and 
do not resolve spontaneously with steroids, anticonvulsants, or electrolyte 
correction within 7 days will be considered a DLT 
o Symptomatic CNS hemorrhage of any grade will be considered a DLT 
o > Grade 3 seizure only if the patient requires inpatient hospitalization for 
medical intervention. A breakthrough seizure that is managed with minor 
antiepileptic drug modification will not be considered a DLT. Contact the 
Study Chair for clarification as needed. 
 
• 
Grade 3 and 4 non-hematological, non-CNS toxicities will be considered dose 
limiting with the following exceptions: 
o Grade 3 nausea, vomiting, or diarrhea without sufficient prophylaxis with a 
duration <3 days 
o Insomnia 
o Alopecia 
o Fatigue 
o Grade 3 hyperglycemia that is reversible and without clinical symptoms 
o Grade 3 electrolyte disturbances that are asymptomatic and reversible within 
3 days, and do not re-occur upon continuing or re-initiation at the same dose 
o Grade 3 or 4 hypophosphatemia, unless considered clinically relevant 
o Grade 3 or 4 elevations in alkaline phosphatase 
o Grade 3 hypertension unless inpatient hospitalization is required 
o A subject’s first episode of deep venous thrombosis (DVT) or pulmonary 
embolism will not require dose modification 
 
 
For patients who have begun the fixed dose drug continuation phase and experience a 
new dose-limiting toxicity, the study medication will be held until the DLT has resolved. If 
the DLT resolves within 14 days, the patient may resume therapy at the prior dose level 
(1 dose level reduction). If an additional dose reduction is required, the study medication 
should be discontinued. 
 
 
 

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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
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Dose escalation will proceed for each patient according to the following scheme:  
 
 
Dose Level 
Solriamfetol 
 
+1 
75 mg, p.o. once daily 
+2 
150 mg, p.o. once daily 
+3 
300 mg, p.o. once daily 
 
For patients who experience a dose limiting toxicity, the study drug will be de-escalated 
to the last tolerated dose. For patients who experience a dose-limiting toxicity at dose 
level +1, treatment will be discontinued and the patient will not receive further treatment. 
2. 
Other Agent(s) 
While receiving study drug treatment, patients may continue to receive tumor-directed 
chemotherapy, targeted therapy, or immunotherapy. Patients who are undergoing 
treatment with any of these tumor-directed treatments and who meet the eligibility 
criteria for the study will be able to continue to receive their anti-cancer therapy 
throughout the duration of the study as long as there is no known drug-drug interaction 
between the study drug and anti-cancer therapy. 
3. 
Other Modality(ies) or Procedures 
Patients who are anticipated to undergo surgery or radiation therapy are not permitted to 
receive the study drug as the safety profile has not been defined in the perioperative 
setting or when administered with radiation. 
 
 
10. General Concomitant Medication and Supportive Care Guidelines 
Patients should receive full supportive care, including transfusions of blood and blood products, 
erythropoietin, antibiotics, antiemetics, etc., as clinically indicated. Anti-inflammatory or narcotic 
analgesics may be offered as needed. Medications considered necessary for the patient's well-
being may be given at the discretion of the investigator, i.e., chronic treatments for concomitant 
medical conditions, as well as agents required for life-threatening medical problems, etc. The 
reason(s) for treatment, dosage, and dates of treatment should be recorded on the flow sheets. 
 
It is recommended that patients not be started on a new selective serotonin reuptake inhibitor 
(SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI). Exception will need approval from 
the Study Chair. Patients taking sedative medications or other agents known to interact with 
sleep such as narcotics, benzodiazepines, antipsychotics, melatonin or other agents can be 
continued during the study. The doses of these medications should remain the same throughout 
the active treatment period of the study unless there is a medical indication for dose adjustment 
which will be determined by the patient’s treating physician. Corticosteroids should not be 
initiated unless medically indicated during the active treatment period. All changes in doses and 
new sedative medications, sleep active agents, or corticosteroids should be tracked including 
over-the-counter medications such as Tylenol PM, Benadryl, etc. 

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11. Duration of Therapy 
In the absence of treatment delays due to adverse events, treatment may continue for the 
duration of the study treatment (D70 +7 days) or until one of the following criteria applies: 
 
• 
Disease progression requiring surgery or radiation therapy, 
• 
Intercurrent illness that prevents further administration of treatment, 
• 
Unacceptable adverse event(s), 
• 
Patient decides to withdraw from the study, or 
• 
General or specific changes in the patient's condition render the patient unacceptable for 
further treatment in the judgment of the investigator. 
12. Duration of Follow Up 
Patients will be followed for a minimum of 30 days after the last study drug is administered for 
adverse events monitoring.  
13. Determination of Evaluable Patients 
Patients who enroll in the study but do not take a dose of the study medication will not be 
considered evaluable and will be replaced. In other words, patients who begin the pre-treatment 
baseline assessment and do not take the study medication will not be evaluable and will be 
replaced. 
14. Criteria for Removal from Study 
Patients will be removed from study when any of the criteria listed in section 5.4 applies.  
8 
Dosing Delays/Dose Modifications 
 
During the flexible dose titration period of this study, dose modifications will be performed according to 
the Dose-Limiting Toxicity scheme outlined in Section 6.9.1. 
 
During the fixed dose drug continuation period of this study, for patients who experience a new dose-
limiting toxicity (see Section 6.9.1) treatment dose will be modified according to the following scheme: 
 
 
Dose Level 
Insert Agent Name Dose 
 
+1 
75 mg, p.o. once daily 
+2 
150 mg, p.o. once daily 
+3 
300 mg, p.o. once daily 
 
All dose modifications will be recorded, tracked and monitored via a drug diary (Appendices F and G) 
throughout the duration of study treatment. 
 
 

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Wake Forest Baptist Comprehensive Cancer Center 
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Protocol version date 05-19-21 
 
 
 
 
 
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9 
Measurement of Effect 
 
Tumor response and survival outcomes will NOT be included as an endpoint in this study. MRI Brain is 
included to track evidence of clinically documented progressive disease which could contribute to 
changes in patient-reported and clinician assessed outcome measures (see Section 7.8). 
10 Adverse Events List and Reporting Requirements 
1. Adverse Event List for solriamfetol 
In the 12-week placebo-controlled studies in patients with narcolepsy and OSA, in the overall 
population the most frequent (≥5%) adverse events that also had a higher incidence with 
solriamfetol than with placebo were: 
 
• 
Headache (11-21%) 
• 
Nausea (8-11%) 
• 
Decreased appetite (8-11%) 
• 
Anxiety (6-7%) 
• 
Diarrhea (5-6%) 
• 
Dry mouth (5-6%) 
• 
Insomnia (5-8%) 
 
Less common adverse events occurring at a rate of ≥1% in the combined solriamfetol treatment 
group and higher than the placebo rate are shown in Table 2. 
 
Patients with OSA who completed either of the two 12 –week placebo-controlled clinical trials, 
as well as patients with narcolepsy who completed a previous clinical trial of solriamfetol in the 
treatment of excessive sleepiness were eligible to participate in a study to evaluate the long-
term safety and maintenance of efficacy of solriamfetol. The most common Treatment 
Emergent Adverse Events (TEAEs, ≥ 5% in combined solriamfetol groups for any indication) 
in the safety population across the entire study were: 
 
• 
Headache (11%) 
• 
Nausea (8.9%) 
• 
Insomnia (7.9%) 
• 
Nasopharyngitis (8.4%) 
• 
Dry mouth (7.3%) 
• 
Anxiety (7.2%) 
• 
Decreased appetite (5.0%), and 
• 
Upper respiratory tract infection (5.0%) 
 
 
 
Serious TEAEs were reported in 27 (4.2%) patients across all phases. There were a total of 9 
patients with 9 cardiovascular or potential cardiovascular serious TEAEs: 
 
• 
2 cases of atrial fibrillation 
• 
1 case of acute myocardial infarction 
• 
1 case of angina pectoris 
• 
1 case of chest discomfort 

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Wake Forest Baptist Comprehensive Cancer Center 
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• 
1 case of chest pain 
• 
1 case of non-cardiac chest pain 
• 
1 case of cerebrovascular accident, and  
• 
1 case of pulmonary embolism 
 
There was one death due to sepsis, which occurred in a 70-year old immunosuppressed male 
with OSA on SUNOSI 300 mg. The death was considered unrelated to study drug by the 
investigator. 
 
Table 2: Common Adverse Drug Reactions in the 12-Week Placebo-controlled Parallel Group 
Studies in Narcolepsy and Obstructive Sleep Apnea Overall and by Indication (Safety Population) 
 
System Organ Class 
Adverse Reaction, n (%) 
Narcolepsy & OSA 
Narcolepsy 
OSA 
Placeb
o 
(N=226) 
Combined 
solriamfetol 
(N=573) 
Placeb
o 
(N=108) 
Combined 
solriamfetol 
(N=220) 
Placeb
o 
(N=118) 
Combined 
solriamfetol 
(N=353) 
Cardiac Disorders 
Palpitations 
1 (<1.0) 
14 (2) 
1 (<1.0) 
6 (3) 
0 
8 (2) 
Gastrointestinal Disorders 
Nausea 
11 (5) 
53 (9) 
4 (4) 
25 (11) 
7 (6) 
28 (8) 
Diarrhea 
5 (2) 
30 (5) 
4 (4) 
13 (6) 
1 (<1.0) 
17 (5) 
Dry Mouth 
4 (2) 
29 (5) 
2 (2) 
13 (6) 
2 (2) 
16 (6) 
Abdominal Paina 
5 (2) 
18 (3) 
3 (3) 
6(3) 
2 (2) 
12 (3) 
Constipation 
2 (<1.0) 
12 (2) 
1 (<1.0) 
6 (3) 
1 (<1.0) 
6 (2) 
Vomiting 
2 (<1.0) 
6 (1) 
1 (<1.0) 
2 (<1.0) 
1 (<1.0) 
4 (1) 
General Disorders and 
Administration Site Conditions 
Feeling Jittery 
0 
17 (3) 
0 
3 (1) 
0 
14 (4) 
Chest discomfort 
0 
10 (2) 
0 
1 (<1.0) 
0 
9 (3) 
Investigations 
Heart rate increased 
0 
8 (1) 
0 
5 (2) 
0 
3 (<1.0) 
Blood Pressure increased 
1 (<1.0) 
7 (1) 
1 (<1.0) 
3 (1) 
0 
4 (1) 
Weight decreased 
0 
7 (1) 
0 
5 (2) 
0 
2 (<1.0) 
Metabolism and Nutrition Disorders 
Decreased appetite 
2 (<1.0) 
52 (9) 
1 (<1.0) 
25 (11) 
1 (<1.0) 
27 (8) 
Nervous System Disorders 
Headacheb 
18 (8) 
84 (15) 
8 (7) 
46 (21) 
10 (8) 
38 (11) 
Dizziness 
4 (2) 
19 (3) 
3 (3) 
9 (4) 
1 (<1.0) 
10 (3) 
Psychiatric Disorders 
Anxiety 
1 (<1.0) 
39(7) 
1 (<1.0) 
14 (6) 
0 
25 (7) 
Insomniac 
7 (3) 
33 (6) 
4 (4) 
17 (8) 
3 (3) 
16 (5) 
Irritability 
1 (<1.0) 
13 (2) 
1 (<1.0) 
5 (2) 
0 
8 (2) 
Bruxism 
0 
8 (1) 
0 
4 (2) 
0 
4 (1) 
Agitation 
1 (<1.0) 
7 (1) 
0 
4 (2) 
1 (<1.0) 
3 (<1.0) 
Respiratory, Thoracic and 
Mediastinal Disorders 
Cough 
0 
10 (2) 
0 
3 (1) 
0 
7 (2) 
Skin and Subcutaneous 
Tissue Disorders 
Hyperhidrosis 
0 
9 (2) 
0 
3 (1) 
0 
6 (2) 
Vascular Disorders 
Hypertension 
0 
6 (1) 
0 
0 
0 
6 (2) 
 
Adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA), Version 18.0. 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
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                                              Page 36 of 83 
Percentages are subject incidences based on N, number of subjects within each treatment group in safety population 
treated in 12-week randomized studies ADX-N05 202, 14-002 and 14-003.Common adverse reactions are those 
occurring at a rate of ≥1% in the combined JZP- 110 treatment group and higher than the placebo rate. Events occurring 
at a rate of >1% were rounded to the nearest whole percent. Events occurring <1% are noted as such.aAbdominal pain is 
a combined term of ‘abdominal pain,’ ‘abdominal pain upper,’ and ‘abdominal discomfort.bAdverse reaction 
‘Headache’ is a combined term of ‘headache,’ ‘tension headache,’ and ‘head discomfort.cInsomnia’ is a combined term 
of ‘insomnia,’ ‘initial insomnia,’ ‘middle insomnia,’ and ‘terminal insomnia. 
 
Adverse Event Characteristics 
 
• 
CTCAE term (AE description) and grade:  The descriptions and grading scales found in 
the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will 
be utilized for AE reporting. All appropriate treatment areas should have access to a copy of 
the CTCAE version 5.0. A copy of the CTCAE version 5.0 can be downloaded from the 
CTEP web site (http://ctep.cancer.gov). 
 
• 
‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ (see Section 7.1 above) for 
expedited reporting purposes only.   
 
• 
Attribution of the AE: 
 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE is doubtfully related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
 
2. DSMC SAE Reporting Requirements 
The Data and Safety Monitoring Committee (DSMC) is responsible for reviewing SAEs for 
WFBCCC Institutional studies as outlined in Appendix B. DSMC currently requires that all 
unexpected 4 and all grade 5 SAEs on these trials be reported to them for review. All WFBCCC 
Clinical Research Management (CRM) staff members assisting a Principal Investigator in 
investigating, documenting and reporting an SAE qualifying for DSMC reporting are responsible 
for informing a clinical member of the DSMC as well as the entire committee via the email 
notification procedure of the occurrence of an SAE.  
3. WFUHS IRB AE Reporting Requirements 
Any unanticipated problems involving risks to subjects or others and adverse events shall be 
promptly reported to the IRB, according to institutional policy. Reporting to the IRB is required 
regardless of the funding source, study sponsor, or whether the event involves an 
investigational or marketed drug, biologic or device. Reportable events are not limited to 
physical injury, but include psychological, economic and social harm. Reportable events may 
arise as a result of drugs, biological agents, devices, procedures or other interventions, or as a 
result of questionnaires, surveys, observations or other interactions with research subjects. 
 
All members of the research team are responsible for the appropriate reporting to the IRB and 
other applicable parties of unanticipated problems involving risk to subjects or others. The 
Principal Investigator, however, is ultimately responsible for ensuring the prompt reporting of 
unanticipated problems involving risk to subjects or others to the IRB. The Principal Investigator 
is also responsible for ensuring that all reported unanticipated risks to subjects and others which 
they receive are reviewed to determine whether the report represents a change in the risks 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
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                                              Page 37 of 83 
and/or benefits to study participants, and whether any changes in the informed consent, 
protocol or other study-related documents are required. 
 
Any unanticipated problems involving risks to subjects or others occurring at a site where the 
study has been approved by the WFUHS IRB (internal events) must be reported to the WFUHS 
IRB within 7 calendar days of the investigator or other members of the study team becoming 
aware of the event. 
 
Any unanticipated problems involving risks to subjects or others occurring at another site 
conducting the same study that has been approved by the WFUHS IRB (external events) must 
be reported to the WFUHS IRB within 7 calendar days of the investigator or other members of 
the study team becoming aware of the event. 
Any event, incident, experience, or outcome that alters the risk versus potential benefit of the 
research and as a result warrants a substantive change in the research protocol or informed 
consent process/document in order to insure the safety, rights or welfare of research subjects. 
4. Sponsor Reporting Requirements  
 
WFBMC will and will ensure that the Investigator complies with Applicable Law in connection 
with the study, including but not limited to providing all adverse drug experience reports and 
notifications by the relevant Governmental Authority. 
 
All serious adverse events that require reporting per the Protocol and which occur in a subject 
wo received the Product as part of the study will be reported by email 
(AEreporting@jazzpharma.com) to Jazz Pharmaceuticals not later than 1 buisness day 
following WFBMCs receipt of notice of such occurrence.  In addition, WFBMC will ensure that 
the Investigator provides a copy of all final reports regarding such adverse events that are 
provided by WFBMC or Investigator to the relevant Governmental Authority, which reports will 
be provided by email (PVcomms@jazzpharma.com) to Jazz Pharmaceucitcals at the time of 
submission to the Governmental Autorhity.  All other adverse events will be reported to Jazz 
Pharmaceuticals (PVcomms@jazzpharma.com) in summary or line-item form upon written 
request and at the conclusion of the study.   
11 Pharmaceutical Information 
 
A list of the adverse events and potential risks associated with the investigational or commercial agents 
administered in this study can be found in Section 9.0. 
 
1. Pharmaceutical Accountability 
Drug accountability logs will be maintained for all agents used under this protocol. These logs 
shall record quantities of study drug received and quantities dispensed to patients, including lot 
number, date dispensed, patient identifier number, patient initials, protocol number, dose, 
quantity returned, balance remaining, and the initials of the person dispensing the medication.  
 
2. Solriamfetol 44 
 
 
Chemical Name: (R)-2-amino-3-phenylpropylcarbamate hydrochloride 
 
Other Names: JZP-110, ADX-N05. 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 38 of 83 
 
Chemical Structure:   
 
 
Pharmaceutical Properties: solriamfetol is a late-stage investigational wakefulness promoting 
agent in clinical development for the treatment of excessive daytime sleepiness (EDS) in adult 
patients with conditions including narcolepsy or obstructive sleep apnea. Solriamfetol is a 
phenylalanine derivative with dopaminergic and noradrenergic activity. Its mechanism of action, 
although not fully determined, includes low potency dopamine and norepinephrine reuptake 
inhibition.44 It is distinct from modafinil and traditional stimulants used in patients with EDS. 
 
Formulations: solriamfetol is formulated as an immediate release tablet available in 75 mg, 150 
mg, and 300 mg strengths. The agent is supplied by Jazz Pharmaceuticals, INC. Packaging?  
 
Route of Administration: Oral, given with or without food. Each dose should be taken with 8 
ounces (240 mL) of water. 
 
Storage Requirements: solriamfetol tablets are to be stored at room-temperature conditions, 
15°C to 30°C (59°F to 86°F). 
 
Stability:  Studies are ongoing to monitor the stability of solriamfetol tablets. 
12 Data Management 
 
Informed consent document 
EPIC 
Protocol registration form 
OnCore 
Adverse Events Log (Appendix E) 
OnCore 
Patient Drug Diary (Appendix F) 
 
Fixed Dose Patient Drug Diary (Appendix G) 
 
Epworth Sleepiness Scale (Appendix H) 
 
Pittsburgh Sleep Quality Index (Appendix I) 
 
Brief Fatigue Inventory (Appendix J) 
 
Cancer Fatigue Scale (Appendix K) 
 
Beck’s Depression Inventory (Appendix L) 
 
Neurocognitive Battery Form (Appendix M) 
 
FACT-Br (Appendix N) 
 
Concurrent Medication (Appendix O) 
OnCore 
Off-Study Form (Appendix P) 
OnCore 
MR Imaging Record (Appendix Q) 
 
Sleep Diary and Actigraphy Record (Appendix R) 
 
Glioma History (Appendix S) 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
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                                              Page 39 of 83 
13 Statistical Considerations 
 
This is a single-arm, open label, non-randomized safety study in patients with stable glioma disease. 
The primary outcome is safety of oral solriamfetol as doses of 75 mg daily, 150 mg daily and 300 mg 
daily. Secondary outcomes include ESS score, PSQI score, a composite neurocognitive battery score, 
FSS score, BDI score, and FACT-Br score. 
 
1. Analysis of Primary Objective 
 
For the primary outcome, NCI Common Terminology Criteria for Adverse Events (CTCAE) 
version 5.0 will be used for scoring toxicity and adverse events. 
 
The severity and frequency of toxicity and adverse events for each dose of solriamfetol will be 
tabulated using descriptive statistics. The proportions of subjects who experienced grade 3 or 
above toxicities will be estimated, along with 95% confidence intervals by each type of toxicity. 
 
To compare the safety of solriamfetol at 75 mg daily, 150 mg daily, 300 mg daily, chi-squared 
statistics will be used. If there are some cells with expected value <5, Fisher’s exact test will be 
used for the comparison. 
 
2. Analysis of Secondary Objective 
For the secondary outcomes, descriptive statistics will be performed for each of the outcome 
measures. Changes in pre- and post-treatment scores will be assessed and compared using the 
pair-t tests if the changes follow a normal distribution and using the Wilcoxon signed rank tests if 
the changes do not follow a normal distribution. For the comparison between the change in ESS 
score in the study patients and the published change score in patients with obstructive sleep 
apnea, we will use the one sample t-test for this comparison. 
 
3. Analysis of Exploratory Objective 
13.3.1 To explore the dose response effect of solriamfetol on actigraphy, linear regression 
models will be used where the dosage will be treated as an ordinal variable. 
Transformation of actigraphy will be performed to satisfy the normality assumption if 
needed. 
 
13.3.2 The analysis will be the same as that specified in 13.1. 
 
4. Power and Sample Size 
We plan to recruit around 36 participants. 
 
In the prior phase 2a and phase 2b studies in patients with narcolepsy which had similar sample 
sizes, no patients in the phase 2a and three patients in the phase 2b study required 
discontinuation of study medication, though two of these discontinuations were not attributed to 
the study drug.46,47 In the prior phase 3 study, 9 patients (9%) including one in the 75 mg arm, 3 
in the 150 mg arm, and 5 in the 300 mg arm required discontinuation due to treatment related 
AEs.45 In the current study, 36 patients will receive 75 mg daily dosing. We conservatively 
estimate that at least 33 patients will escalate to 150 mg daily, and at least 30 patients will 
escalate to receive 300 mg daily. These estimates are felt to be overly conservative based on 
data from these prior studies in patients narcolepsy. 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
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From prior studies, the most common adverse event proportions range from 10% to 20%. 
Assuming 10% and 20% of adverse event proportion, the detectable proportions for the 
combined dosage are 24% and 36%, respectively, in order to reach 80% power at a significance 
level of 0.1 (given the pilot nature of this study) and a two-sided test.  These detectable 
proportions are reasonable.  If we observe an adverse event proportion in the patients with 
primary gliomas that is higher than 36%, then the adverse event proportion is significantly 
higher than the other study populations. In practice, if an adverse event proportion is higher than 
50%, then the safety/tolerability of solriamfetol needs to be questioned. We should have enough 
power for this primary analysis. Note that this study allows us to determine safety profiles for the 
3 doses of solriamfetol. It is primarily for descriptive purpose and to generate data on safety and 
estimation of effect size for the design of a subsequent randomized study powered to determine 
drug activity. The results generated from this study will be beneficial for the future research 
study. 
 
ESS score is the most important secondary outcome in this study. We also calculate the power 
to test whether the pre-post change is different from 0 and test whether the change is different 
from the pre-post change in the prior studies which recorded the pre-post changes for patients 
at 75 mg, 150 mg, and 300 mg. At an alpha of 0.10, a two-sided test, and cohort sample size of 
36 patients, the study will have 80% power to detect the mean difference of 1.01 point (=0.42 
standard deviation (SD)) in ESS score from the study sample. The mean differences are 
reasonable. We should have enough power for our analysis. 
 
Prior studies of solriamfetol in patients with narcolepsy have demonstrated improvement in ESS 
scores at Week 8 of -3.4 (75 mg daily), -5.2 (150 mg daily), -6.4 (300 mg daily), and -2.1 
(placebo) with baseline ESS ranging from 16.9-17.3. In patients with OSA, Week 8 
improvements were -6.3 (75 mg daily), -6.9 (150 mg daily), -7.7 (300 mg daily), and -3.8 
(placebo) in patients with baseline ESS ranging from 14.8 to 15.6. In our prior study mean ESS 
score for patients with primary brain tumors who would be eligible for the proposed study (i.e. 
ESS>10) was 14.8 (SD: 2.4). For the current study, we will use the data from the prior OSA 
study as a comparator given that baseline ESS scores were similar to what we anticipate in the 
to-be-enrolled cohort. Based on this, the study hypothesizes that treatment with solriamfetol at 
75 mg, 150 mg, or 300 mg will achieve at least a 6.3 point difference (75 mg daily) and up to 7.7 
point different (300 mg daily) in ESS scores at Week 10 (baseline vs V3). This will be compared 
to a null difference of 3.8 (placebo arm in OSA study). This mean change in ESS scores is 
clinically meaningful as has been reported.53 In order to detect the differences between the 
mean change ESS score from the proposed study to the mean change of 3.8 in the placebo arm 
in OSA study, the detectable mean change needs to be greater than 5.4 in the study sample in 
order to reach 80% power. We hypothesize that the mean change in this study sample ranges 
from 6.3 to 7.7, which is higher than 5.4. We should have sufficient power to detect the 
difference between the mean change ESS score in our study sample and that in the placebo 
arm in the OSA study. 
5. Estimated Accrual Rate 
The target population includes WHO Grade 2, Grade 3, and Grade 4 gliomas. The median 
survival for each of these tumors is approximately 10-15 years, 2-7 years, and 20 months, 
respectively. WHO Grade 4 gliomas (median OS ~20 months) are included in this study to 
address the safety of this agent. 
 
Ultimately, long term treatment could be most beneficial for those with WHO Grade 2-3 tumors 
where the sleep-fatigue symptom cluster is a significant problem for long term survivorship. 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 41 of 83 
Furthermore, these pilot data will not only inform subsequent drug development of solriamfetol 
in this population but also in other cancer patients receiving or having completed chemo-
radiotherapy, in neurologically diseased patients taking antiepileptics, or patients prescribed 
corticosteroids. 
6. Estimated Study Length 
Anticipated Enrollment Duration: 18 months 
 
Anticipated Treatment Duration: 24 months (18 month enrollment + 6 month on and post-
treatment follow up) 
 
Total Study Duration from first patient enrollment to end: 2 years 
Anticipated Patient Enrollment per month: 2 
 
Total Anticipated Patient Enrollment: 36 
 
7. Interim Analysis Plan 
Interim analysis of safety data will be performed when all 36 evaluable patients have 
completed dose escalation. Interim analysis of secondary efficacy endpoints is not planned. 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 42 of 83 
References 
 
1.  
Davidson JR, Maclean AW, Brundage MD, Schulze K. Sleep Disturbance in Cancer Patients. Vol 54.; 
2002. https://ac.els-cdn.com/S0277953601000430/1-s2.0-S0277953601000430-
main.pdf?_tid=307c24ca-d606-4555-87f7-
df0fa5acfa4b&acdnat=1533562609_4321329f891f040073bcccf35c5200b2. Accessed August 6, 2018. 
2.  
Savard J, Simard MPs S, Blanchet MPs J, Ivers MPs H, Morin CM. Prevalence, Clinical Characteristics, 
and Risk Factors for Insomnia in the Context of Breast Cancer. Vol 24.; 2001. 
https://academic.oup.com/sleep/article-abstract/24/5/583/2750058. Accessed August 6, 2018. 
3.  
Lee K, Cho M, Miaskowski C, Dodd M. Impaired sleep and rhythms in persons with cancer. Sleep Med 
Rev. 2004;8(3):199-212. doi:10.1016/j.smrv.2003.10.001 
4.  
Savard J, Morin CM. Insomnia in the Context of Cancer : A Review of a Neglected Problem. JCO. 
2001;19(3):895-908. 
5.  
Palesh OG, Roscoe JA, Mustian KM, et al. Prevalence, Demographics, and Psychological Associations 
of Sleep Disruption in Patients With Cancer: University of Rochester Cancer Center-Community Clinical 
Oncology Program. J Clin Oncol. 2009;28:292-298. doi:10.1200/JCO.2009.22.5011 
6.  
Otte JL, Carpenter JS, Russell KM, Bigatti S, Champion VL. Prevalence, Severity, and Correlates of 
Sleep-Wake Disturbances in Long-Term Breast Cancer Survivors. J Pain Symptom Manag. 
2010;39(3):535-547. doi:10.1016/j.jpainsymman.2009.07.004 
7.  
Armstrong TS, Shade MY, Breton G, et al. Sleep-wake disturbance in patients with brain tumors. Neuro 
Oncol. 2017;19(3):323-335. doi:10.1093/neuonc/now119 
8.  
Boele FW, Douw L, de Groot M, et al. The effect of modafinil on fatigue, cognitive functioning, and mood 
in primary brain tumor patients: a multicenter randomized controlled trial. Neuro Oncol. 
2013;15(10):1420-1428. doi:10.1093/neuonc/not102 
9.  
Faithfull S, Brada M. Somnolence syndrome in adults following cranial irradiation for primary brain 
tumours. Clin Oncol. 1998;10(4):250-254. doi:10.1016/S0936-6555(98)80011-3 
10.  
Faithfull S. Patients’ experiences following cranial radiotherapy: a study of the somnolence syndrome. J 
Adv Nurs. 1991;16(8):939-946. doi:10.1111/j.1365-2648.1991.tb01798.x 
11.  
Powell C, Guerrero D, Sardell S, et al. Somnolence syndrome in patients receiving radical radiotherapy 
for primary brain tumours: A prospective study. Radiother Oncol. 2011;100:131-136. 
doi:10.1016/j.radonc.2011.06.028 
12.  
Gapstur R, Gross CR, Ness K. Factors Associated With Sleep-Wake Disturbances in Child and Adult 
Survivors of Pediatric Brain Tumors: A Review. Oncol Nurs Forum. 2009;36(6):723-731. 
doi:10.1188/09.ONF.723-731 
13.  
Gapstur R, Gross CR, Ness K. Factors Associated With Sleep-Wake Disturbances in Child and Adult 
Survivors of Pediatric Brain Tumors: A Review. Oncol Nurs Forum. 2009;36(6):723-731. 
doi:10.1188/09.ONF.723-731 
14.  
Müller HL, Handwerker G, Wollny B, Faldum A, Sörensen N. Melatonin Secretion and Increased 
Daytime Sleepiness in Childhood Craniopharyngioma Patients. J Clin Endocrinol Metab. 
2002;87(8):3993-3996. doi:10.1210/jcem.87.8.8751 
15.  
Valko PO, Siddique A, Linsenmeier C, Zaugg K, Held U, Hofer S. Prevalence and predictors of fatigue in 
glioblastoma: a prospective study. Neuro Oncol. 2015;17(2):274-281. doi:10.1093/neuonc/nou127 
16.  
Ray M, Rogers LQ, Trammell RA, Toth LA. Fatigue and sleep during cancer and chemotherapy: 
translational rodent models. Comp Med. 2008;58(3):234-245. 
http://www.ncbi.nlm.nih.gov/pubmed/18589865. Accessed August 6, 2018. 
17.  
Palesh O, Peppone L, Innominato PF, et al. Prevalence, putative mechanisms, and current 
management of sleep problems during chemotherapy for cancer. Nat Sci Sleep. 2012;4:151-162. 
doi:10.2147/NSS.S18895 
18.  
Jones LW, Guill B, Keir ST, et al. Patterns of exercise across the cancer trajectory in brain tumor 
patients. Cancer. 2006;106(10):2224-2232. doi:10.1002/cncr.21858 
19.  
Dickerson SS, Connors LM, Fayad A, Dean GE. Sleep-wake disturbances in cancer patients: narrative 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
                                              Page 43 of 83 
review of literature focusing on improving quality of life outcomes. Nat Sci Sleep. 2014;6:85-100. 
doi:10.2147/NSS.S34846 
20.  
Fiorentino L, Rissling M, Liu L, Ancoli-Israel S. The Symptom Cluster of Sleep, Fatigue and Depressive 
Symptoms in Breast Cancer Patients: Severity of the Problem and Treatment Options. Drug Discov 
Today Dis Models. 2011;8(4):167-173. doi:10.1016/j.ddmod.2011.05.001 
21.  
Die Trill M. Anxiety and sleep disorders in cancer patients. EJC Suppl  EJC  Off J EORTC, Eur Organ 
Res Treat Cancer . [et al]. 2013;11(2):216-224. doi:10.1016/j.ejcsup.2013.07.009 
22.  
Cleeland CS, Bennett GJ, Dantzer R, et al. Are the symptoms of cancer and cancer treatment due to a 
shared biologic mechanism? Cancer. 2003;97(11):2919-2925. doi:10.1002/cncr.11382 
23.  
Rich T, Innominato PF, Boerner J, et al. Elevated Serum Cytokines Correlated with Altered Behavior, 
Serum Cortisol Rhythm, and Dampened 24-Hour Rest-Activity Patterns in Patients with Metastatic 
Colorectal Cancer. Clin Cancer Res. 2005;11(5):1757-1764. doi:10.1158/1078-0432.CCR-04-2000 
24.  
Vitkovic L, Konsman JP, Bockaert J, Dantzer R, Homburger V, Jacque C. Cytokine signals propagate 
through the brain. Mol Psychiatry. 2000;5(6):604-615. doi:10.1038/sj.mp.4000813 
25.  
Konsman JP, Parnet P, Dantzer R. Cytokine-induced sickness behaviour: mechanisms and implications. 
Trends Neurosci. 2002;25(3):154-159. doi:10.1016/S0166-2236(00)02088-9 
26.  
Quan N, Banks WA. Brain-immune communication pathways. Brain Behav Immun. 2007;21(6):727-735. 
doi:10.1016/J.BBI.2007.05.005 
27.  
Sartori AC, Vance DE, Slater LZ, Crowe M. The impact of inflammation on cognitive function in older 
adults: implications for healthcare practice and research. J Neurosci Nurs. 2012;44(4):206-217. 
doi:10.1097/JNN.0b013e3182527690 
28.  
Chen J-C, Espeland MA, Brunner RL, et al. Sleep duration, cognitive decline, and dementia risk in older 
women. Alzheimers Dement. 2016;12(1):21-33. doi:10.1016/j.jalz.2015.03.004 
29.  
Clark IA, Vissel B. Inflammation-sleep interface in brain disease: TNF, insulin, orexin. J 
Neuroinflammation. 2014;11(1):51. doi:10.1186/1742-2094-11-51 
30.  
Kreutzmann JC, Havekes R, Abel T, Meerlo P. Sleep deprivation and hippocampal vulnerability: 
changes in neuronal plasticity, neurogenesis and cognitive function. Neuroscience. 2015;309:173-190. 
doi:10.1016/j.neuroscience.2015.04.053 
31.  
Shokri-Kojori E, Wang G-J, Wiers CE, et al. β-Amyloid accumulation in the human brain after one night 
of sleep deprivation. Proc Natl Acad Sci U S A. 2018;115(17):4483-4488. doi:10.1073/pnas.1721694115 
32.  
Zhu B, Dong Y, Xu Z, et al. Sleep disturbance induces neuroinflammation and impairment of learning 
and memory. Neurobiol Dis. 2012;48(3):348-355. doi:10.1016/j.nbd.2012.06.022 
33.  
De Berardis D, Marini S, Fornaro M, et al. The melatonergic system in mood and anxiety disorders and 
the role of agomelatine: implications for clinical practice. Int J Mol Sci. 2013;14(6):12458-12483. 
doi:10.3390/ijms140612458 
34.  
Wion D, Berger F, Wion-Barbot N. Glioma, melatonin, and radiotherapy. Cancer Res. 2006;66(12):6457. 
doi:10.1158/0008-5472.CAN-06-0437 
35.  
Kassayová M, Ahlersová E, Ahlers I. Two-phase response of rat pineal melatonin to lethal whole-body 
irradiation with gamma rays. Physiol Res. 1999;48(3):227-230. 
http://www.ncbi.nlm.nih.gov/pubmed/10523060. Accessed August 6, 2018. 
36.  
Müller HL, Handwerker G, Wollny B, Faldum A, Sörensen N. Melatonin Secretion and Increased 
Daytime Sleepiness in Childhood Craniopharyngioma Patients. J Clin Endocrinol Metab. 
2002;87(8):3993-3996. doi:10.1210/jcem.87.8.8751 
37.  
Scheff JD, Calvano SE, Lowry SF, Androulakis IP. Modeling the influence of circadian rhythms on the 
acute inflammatory response. J Theor Biol. 2010;264(3):1068-1076. doi:10.1016/J.JTBI.2010.03.026 
38.  
Cleeland CS, Bennett GJ, Dantzer R, et al. Are the symptoms of cancer and cancer treatment due to a 
shared biologic mechanism? Cancer. 2003;97(11):2919-2925. doi:10.1002/cncr.11382 
39.  
Zotter H, Kerbl R, Millner M, Kurz R. Methylphenidate and melatonin for sleep disorder with optic glioma. 
J Am Acad Child Adolesc Psychiatry. 2001;40(9):992-993. doi:10.1097/00004583-200109000-00004 
40.  
Berk L, Berkey B, Rich T, et al. Randomized phase II trial of high-dose melatonin and radiation therapy 
for RPA class 2 patients with brain metastases (RTOG 0119). Int J Radiat Oncol Biol Phys. 

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Wake Forest Baptist Comprehensive Cancer Center 
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                                              Page 44 of 83 
2007;68(3):852-857. doi:10.1016/j.ijrobp.2007.01.012 
41.  
Gehring K, Patwardhan SY, Collins R, et al. A randomized trial on the efficacy of methylphenidate and 
modafinil for improving cognitive functioning and symptoms in patients with a primary brain tumor. J 
Neurooncol. 2012;107(1):165-174. doi:10.1007/s11060-011-0723-1 
42.  
Lee EQ, Muzikansky A, Drappatz J, et al. A randomized, placebo-controlled pilot trial of armodafinil for 
fatigue in patients with gliomas undergoing radiotherapy. Neuro Oncol. 2016;18(6):849-854. 
doi:10.1093/neuonc/now007 
43.  
Page BR, Shaw EG, Lu L, et al. Phase II double-blind placebo-controlled randomized study of 
armodafinil for brain radiation-induced fatigue. Neuro Oncol. 2015;17(10):1393-1401. 
doi:10.1093/neuonc/nov084 
44.  
Baladi MG, Forster MJ, Gatch MB, et al. Characterization of the Neurochemical and Behavioral Effects 
of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor. J Pharmacol 
Exp Ther. 2018;366(2):367-376. doi:10.1124/jpet.118.248120 
45.  
Thorpy MJ, Dauvilliers Y, Shapiro C, et al. A randomized, placebo-controlled, phase 3 study of the 
safety and efficacy of solriamfetol (JZP-110) for the treatment of excessive sleepiness in patients with 
narcolepsy. Sleep Med. 2017;40:e327. doi:10.1016/j.sleep.2017.11.961 
46.  
Ruoff C, Swick TJ, Doekel R, et al. Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness 
in Adults with Narcolepsy: A Phase 2b Study. Sleep. 2016;39(7):1379-1387. doi:10.5665/sleep.5968 
47.  
Bogan RK, Feldman N, Emsellem HA, et al. Effect of oral JZP-110 (ADX-N05) treatment on wakefulness 
and sleepiness in adults with narcolepsy. Sleep Med. 2015;16(9):1102-1108. 
doi:10.1016/J.SLEEP.2015.05.013 
48.  
Abad VC, Guilleminault C. Solriamfetol for the treatment of daytime sleepiness in obstructive sleep 
apnea. Expert Rev Respir Med. October 2018:1-13. doi:10.1080/17476348.2018.1541742 
49.  
Strollo P, Redline S, Hedner H, et al. A Phase 3, Placebo-Controlled, Randomized-Withdrawal, Double-
Blind, 6-week Multicenter Study of the Safety and Efficacy of JZP-110 for the Treatment of Excessive 
Sleepiness in Participants with Obstructive Sleep Apnea. Sleep. 2017;40(suppl_1):A238-A238. 
doi:10.1093/sleepj/zsx050.643 
50.  
Ruoff C, Swick TJ, Doekel R, et al. Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness 
in Adults with Narcolepsy: A Phase 2b Study. Sleep. 2016;39(7):1379-1387. doi:10.5665/sleep.5968 
51.  
Nolan VG, Gapstur R, Gross CR, et al. Sleep disturbances in adult survivors of childhood brain tumors. 
Qual Life Res. 2013;22(4):781-789. doi:10.1007/s11136-012-0208-5 
52.  
Buysse DJ, Hall ML, Strollo PJ, et al. Relationships between the Pittsburgh Sleep Quality Index (PSQI), 
Epworth Sleepiness Scale (ESS), and clinical/polysomnographic measures in a community sample. J 
Clin Sleep Med. 2008;4(6):563-571. http://www.ncbi.nlm.nih.gov/pubmed/19110886. Accessed August 
6, 2018. 
53.  
Scrima L, Emsellem HA, Becker PM, et al. Identifying clinically important difference on the Epworth 
Sleepiness Scale: results from a narcolepsy clinical trial of JZP-110. Sleep Med. 2017;38:108-112. 
doi:10.1016/J.SLEEP.2017.07.006 
54.  
Mehta MP, Shapiro WR, Glantz MJ, et al. Lead-In Phase to Randomized Trial of Motexafin Gadolinium 
and Whole-Brain Radiation for Patients With Brain Metastases: Centralized Assessment of Magnetic 
Resonance Imaging, Neurocognitive, and Neurologic End Points. J Clin Oncol. 2002;20(16):3445-3453. 
doi:10.1200/JCO.2002.07.500 
55.  
Meyers CA, Smith JA, Bezjak A, et al. Neurocognitive Function and Progression in Patients With Brain 
Metastases Treated With Whole-Brain Radiation and Motexafin Gadolinium: Results of a Randomized 
Phase III Trial. J Clin Oncol. 2004;22(1):157-165. doi:10.1200/JCO.2004.05.128 
56.  
Schagen SB, Klein M, Reijneveld JC, et al. Monitoring and optimising cognitive function in cancer 
patients: Present knowledge and future directions. EJC Suppl. 2014;12(1):29-40. 
doi:10.1016/j.ejcsup.2014.03.003 
57.  
Shaw EG, Rosdhal R, D’Agostino RB, et al. Phase II Study of Donepezil in Irradiated Brain Tumor 
Patients: Effect on Cognitive Function, Mood, and Quality of Life. J Clin Oncol. 2006;24(9):1415-1420. 
doi:10.1200/JCO.2005.03.3001 

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                                              Page 45 of 83 
58.  
Baschnagel A, Wolters PL, Camphausen K. Neuropsychological testing and biomarkers in the 
management of brain metastases. Radiat Oncol. 2008;3:26. doi:10.1186/1748-717X-3-26 
59.  
Krishnasamy M. Fatigue in advanced cancer — meaning before measurement? Int J Nurs Stud. 
2000;37(5):401-414. doi:10.1016/S0020-7489(00)00019-5 
60.  
Barsevick AM, Cleeland CS, Manning DC, et al. ASCPRO recommendations for the assessment of 
fatigue as an outcome in clinical trials. J Pain Symptom Manage. 2010;39(6):1086-1099. 
doi:10.1016/j.jpainsymman.2010.02.006 
61.  
Mendoza TR, Wang XS, Cleeland CS, et al. The rapid assessment of fatigue severity in cancer patients: 
use of the Brief Fatigue Inventory. Cancer. 1999;85(5):1186-1196. 
http://www.ncbi.nlm.nih.gov/pubmed/10091805. Accessed November 8, 2018. 
62.  
Okuyama T, Akechi T, Kugaya A, et al. Development and Validation of the Cancer Fatigue Scale: A 
Brief, Three-Dimensional, Self-Rating Scale for Assessment of Fatigue in Cancer Patients. J Pain 
Symptom Manage. 2000;19(1):5-14. doi:10.1016/S0885-3924(99)00138-4 
63.  
Harris CA, D’Eon JL. Psychometric properties of the Beck Depression Inventory-Second Edition (BDI-II) 
in individuals with chronic pain. Pain. 2008;137(3):609-622. doi:10.1016/j.pain.2007.10.022 
64.  
Mainio A, Hakko H, Timonen M, Niemelä A, Koivukangas J, Räsänen P. Depression in relation to 
survival among neurosurgical patients with a primary brain tumor: a 5-year follow-up study. 
Neurosurgery. 2005;56(6):1234-41; discussion 1241-2. http://www.ncbi.nlm.nih.gov/pubmed/15918939. 
Accessed August 6, 2018. 
65.  
Huang J, Zeng C, Xiao J, et al. Association between depression and brain tumor: a systematic review 
and meta-analysis. Oncotarget. 2017;8(55):94932-94943. doi:10.18632/oncotarget.19843 
 
 

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Appendix A – Eligibility Checklist 
 
 
IRB Protocol No.  
WFBCCC Protocol No. 
Study Title: Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life 
in Patients with Primary Gliomas  
Principal Investigator:  Roy Strowd, MD 
 
Inclusion Criteria 
(as outlined in study protocol) 
Criteria is 
met 
Criteria 
is NOT 
met 
Source Used to 
Confirm * 
(Please 
document dates 
and lab results) 
1 WHO Grade 2-4 infiltrating glioma by histologic confirmation 
• 
Where appropriate results from clinically available testing of isocitrate 
dehydrogenase (IDH) gene mutation status (for all gliomas), chromosome 1p and 
19q deletion status (for suspected oligodendrogliomas), and MGMT gene promoter 
methylation status (for malignant gliomas) must be available in the patient’s chart. 
• 
These studies are standard of care molecular studies that are performed as a part of 
routine clinical practice and allow for integrated molecular subtyping of primary glial 
tumors. 
□ 
□ 
 
2 
Epworth Sleepiness Scale (ESS) score >10 within 21 days of 
enrollment 
□ 
□ 
 
3 
Clinical and/or radiographic evidence of stable disease within 21 
days of enrollment 
□ 
□ 
 
4 
Patients must have completed concurrent chemoradiation with 
recovery of all pre-existing toxicity to CTCAE Grade >1 
• 
Patient who are anticipated to undergo surgery and/or radiation therapy for 
management of their tumor during the duration of study treatment are NOT eligible. 
• 
Patients who are anticipated to undergo adjuvant chemotherapy are eligible as long 
as there is no evidence of tumor progression by clinical exam and/or imaging within 
21 days of enrollment (see 4.1.2). This determination should be made by clinical 
documentation and if there is question discussed with the Study Chair. Adjuvant 
chemotherapy is not an exclusion. 
• 
Patients who are currently undergoing chemotherapy, targeted therapy, 
immunotherapy, or salvage treatment and have stable disease by imaging are 
eligible and can continue the current anti-cancer therapy. Patients who will require a 
new anti-cancer treatment or are anticipated to change anti-cancer treatments are 
not eligible. 
□ 
□ 
 
5 
Age > 18 years 
□ 
□ 
 
6 
Karnofsky performance status ≥ 60% 
□ 
□ 
 
7 
Life expectancy of greater than 4 months 
□ 
□ 
 
8 Patients must have normal organ and marrow function as defined 
below: 
• 
leukocytes 
                                >3,000/mcL 
• 
absolute neutrophil count                 >1,500/mcL 
• 
platelets 
                                >100,000/mcL 
• 
total bilirubin 
                                1.5 X institutional ULN 
• 
AST(SGOT)/ALT(SGPT)                  <2.5 X institutional ULN 
• 
creatinine 
                                within normal institutional limits 
OR 
 
 
• 
creatinine clearance                        >50 mL/min/1.73 m2 for Cre >ULN 
□ 
□ 
 

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WFBCCC 98418 
 
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                                              Page 47 of 83 
9 
The effects of solriamfetol on the developing human fetus are 
unknown. For this reason women of child-bearing potential and 
men must agree to use adequate contraception (hormonal or 
barrier method of birth control; abstinence) prior to study entry 
and for the duration of study participation. Should a woman 
become pregnant or suspect she is pregnant while participating 
in this study, she should inform her treating physician 
immediately 
□ 
□ 
 
10 
Ability to understand and the willingness to sign an IRB-
approved informed consent document (either directly or via a 
legally authorized representative) 
□ 
□ 
 
Exclusion Criteria 
(as outlined in study protocol) 
Criteria 
NOT 
present 
Criteria 
is 
present 
Source Used to 
Confirm * 
(Please 
document dates 
and lab results) 
1 
Receiving active radiation therapy (including patients who are 
within 28 days of completing radiation therapy) 
□ 
□ 
 
2 
Anticipated to undergo radiation therapy or require 
neurosurgical intervention during the period of active treatment 
(i.e. within the next 4 months) 
□ 
□ 
 
3 
Contraindication to solriamfetol based on drug-drug interactions 
or concurrent systemic illness that precludes drug treatment 
□ 
□ 
 
4 
Patients who have not recovered to <CTCAE grade 2 toxicities 
related to prior or current therapy are ineligible. 
• 
Exception for laboratory-based or other adverse event that is stable and not 
anticipated to interfere with study related treatment must be reviewed and approved 
by the Study Chair. 
□ 
□ 
 
5 
Customary bedtime later than midnight 
□ 
□ 
 
6 
Known and/or documented history of obstructive sleep apnea 
(OSA) 
□ 
□ 
 
7 
Uncontrolled behavioral or psychiatric disorder (including 
suicidal ideation) 
□ 
□ 
 
8 
Current excessive caffeine use (>600 mg/day or >6 cups of 
coffee/day) 
□ 
□ 
 
9 
Current or prior history of alcohol or drug abuse within the last 2 
years as assessed by the treating clinician 
□ 
□ 
 
10 
Nicotine dependence that is currently interfering with sleep 
based on assessment by the treating clinician 
□ 
□ 
 
11 Concurrent use of selective serotonin or norepinephrine 
reuptake inhibitors (e.g. SSRI, SNRI) within 14 days of study 
enrollment 
• 
Patients who are currently taking these agents may be tapered at the direction of the 
treating physician prior to study enrollment. 
• 
Patients taking other medications such as narcotics, benzodiazepines, 
antipsychotics, antiepileptics, corticosteroids, or over-the-counter sleep aids can be 
enrolled. It is recommended that the doses of these medications remain the same 
throughout the portion of active study treatment unless there is a medical indication 
for dose adjustment which will be determined by the treating physician (see Section 
7.10). 
□ 
□ 
 
12 
History of allergic reactions attributed to compounds of similar 
chemical or biologic composition to solriamfetol 
□ 
□ 
 

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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
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13 
Uncontrolled intercurrent illness including, but not limited to 
ongoing or active infection, symptomatic congestive heart 
failure, unstable angina pectoris, cardiac arrhythmia, or 
psychiatric illness/social situations that would limit compliance 
with study requirements 
□ 
□ 
 
14 
Pregnant women are excluded from this study because there is 
an unknown but potential risk for adverse events in nursing 
infants secondary to treatment of the mother with –solriamfetol, 
breastfeeding should be discontinued if the mother is treated 
with solriamfetol 
□ 
□ 
 
 
This subject is      
 eligible /  ineligible     for participation in this study. 
 
OnCore Assigned PID: __________________ 
 
 
 
 
 
 
 
 
 
Signature of research professional confirming eligibility: _______________________ Date: _______________ 
 
Signature of Treating Physician:  _____________________________________ Date:  _______________ 
 
Signature of Principal Investigator**:  _____________________________________ Date:  _______________ 
 
* Examples of source documents include clinic note, pathology report, laboratory results, etc. When listing the source, 
specifically state which document in the medical record was used to assess eligibility. Also include the date on the 
document. Example: “Pathology report, 01/01/14” or “Clinic note, 01/01/14” 
 
**Principal Investigator signature can be obtained following registration if needed 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05-19-21 
 
 
 
 
 
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Appendix B – Protocol Registration Form 
 
DEMOGRAPHICS 
Patient: Last Name: _____________________ First Name: ___________________________ 
MRN:          ___ ___ ___ ___ ___ ___ ___ ___ DOB (mm/dd/yy): ___ ___ / ___ ___ / ___ ___ 
ZIPCODE:  ___ ___ ___ ___ ___ 
 
 
SEX:   
  Male      Female 
Ethnicity (choose one):   Hispanic 
Non-Hispanic 
Race (choose all that 
apply): 
 WHITE           BLACK            ASIAN 
 PACIFIC ISLANDER                 NATIVE AMERICAN 
Height:   ___ ___.___ inches 
Weight: ___ ___ ___.___lbs.(actual) 
Surface Area: ___ ___.___m2   
 
Primary Diagnosis: ____________________________________________________________ 
Date of Diagnosis: ___ ___ /___ ___/___ ___ 
 
Performance Status: ___ ___ ___    ECOG   Karnofsky 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Registrar can be contact by calling 
between 8:30 AM and 4:00 PM, Monday – Friday. 
 
Completed Eligibility Checklist and Protocol Registration Form must be hand delivered, faxed or e-mailed to the registrar at 
 
 
 
PROTOCOL INFORMATION 
Date of Registration: 
___ ___ / ___ ___ / ___ ___ 
MD Name (last) : 
______________________       
Date protocol treatment started: 
___ ___ / ___ ___ / ___ ___ 
Informed written consent: 
(consent must be signed prior to registration) 
 YES   NO 
 
Date Consent Signed: 
___ ___ / ___ ___ / ___ ___ 
 
PID # (to be assigned by OnCore): 
___ ___ ___ ___ ___ ___ ___ ___ 
 

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WFBCCC 98418 
 
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Appendix C - Race & Ethnicity Verification Form 
 
 
Thank you so much for helping us to verify your race and ethnicity to ensure the quality of our 
information. As a brief reminder, the information you provide today will be kept confidential. 
 
1. Are you: 
Hispanic or Latino/a 
Not Hispanic or Latino/a 
 
2. What is your race? One or more categories may be selected. 
White or Caucasian 
Black or African American 
American Indian or Alaskan Native 
Asian 
Native Hawaiian or Other Pacific Islander 
Other, Please Specify: ___________________________ 
          
      
 
 
 
 
 
 
 
 
 
Internal use only: 
 
 
 Name: ____________________ MRN#: ____________________  
 
Was the self-reported race and ethnicity of the participant verified at the time of consent? 
Yes        No 
 
Was a discrepancy found?       Yes         No 
         If yes, please provide what is currently indicated in the EMR:  
 
 
Ethnicity: ____________________  
Race: ____________________ 
Additional comments: __________________________________________________________________ 
_____________________________________________________________________________________ 
_____________________________________________________________________________________

 
Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
 
Appendix D – Mandatory DSMC SAE Reporting Guidelines 
 
Data and Safety Monitoring Committee 
(DSMC) Serious Adverse Event (SAE) 
Notification SOP 
Date: 02/11/2021 
 
Mandatory DSMC SAE Reporting Requirements in WISER 
This document describes reporting requirements of adverse events from WFBCCC 
Investigator Initiated interventional trials to the Data and Safety Monitoring Committee 
(DSMC). A trial is considered a WFBCCC Investigator Initiated interventional trial if the 
following criteria are met: 
 
1) The Principal Investigator (PI) of the trial is a member of a department at the 
Wake Forest University Baptist Medical Center. 
2) WFBCCC is considered as the primary contributor to the design, implementation 
and/or monitoring of the trial. 
3) The trial is designated as “Interventional” using the Clinical Research 
Categories definitions provided by the NCI in the Data Table 4 
documentation. 
(https://cancercenters.cancer.gov/GrantsFunding/DataGuide#dt4) 
 
There are two distinct types of WFBCCC Investigator Initiated interventional trials based 
on where patient enrollment occurs.  These include: 
 
1) Local WFBCCC Investigator Initiated interventional trials defined as trials where all 
patients are enrolled from one of the WFBCCC sites. These include the main 
outpatient Cancer Center clinics (located in Winston-Salem) as well as WFBCCC 
affiliate sites located in Bermuda Run (Davie Medical Center), Clemmons, 
Lexington, High Point, or Wilkesboro. 
2) Multi-Center WFBCCC Investigator Initiated interventional trials defined as trials 
where patients are enrolled from other sites in addition to WFBCCC sites.   
There are three types of trials that are included in this category: 
a. Trials sponsored by the NCI Community Oncology Research Program 
(NCORP) that are conducted at multiple sites where the PI is a member of a 
department at the Wake Forest University Baptist Medical Center. 
b. Trials sponsored by Industry that are conducted at multiple sites and the 
PI is a member of a department at the Wake Forest University Baptist 
Medical Center. 
c. Trials sponsored by WFBCCC that are conducted at multiple sites and the 
PI is a member of a department at the Wake Forest University Baptist 
Medical Center. 
 

 
Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
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Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
 
All Adverse Events (AEs) and Serious Adverse Events (SAEs) that occur on any patients 
enrolled on WFBCCC Investigator Initiated Interventional trials must be entered into the 
WISER system. The only exception to this requirement is for patients enrolled on NCORP 
trials at non- WFBCCC sites. AEs and SAEs for NCORP patients enrolled at WFBCCC sites 
must be entered into the WISER system. Once these AEs and SAEs are entered in WISER, 
certain actions must be taken regarding the reporting of specific Adverse Events to the 
DSMC. 
 
 
 
All Adverse Events that occur during protocol intervention (defined below) and are coded 
as either 1) unexpected grade 4, 2) unplanned inpatient hospitalization > 24 hours 
(regardless of grade), or grade 5 (death) must be reported to the DSMC using the using 
the SAE console in WISER. 
 
A research nurse or clinical research coordinator when made aware that an adverse event 
meets one of the above criteria has occurred on a WFBCCC Investigator Initiated 
interventional trial, is responsible for informing a clinical member of the DSMC by phone 
(or in-person) about the adverse event. The nurse/coordinator should contact the treating 
physician prior to calling the DSMC clinical member to obtain all details of the SAE, as well 
as all associated toxicities to be recorded along with the SAE. In addition, this nurse or 
coordinator is responsible for entering the adverse event information into the SAE console 
in WISER.  Once the adverse event has been entered into the SAE console an email 
informing the entire DSMC will be generated. 
 
THESE REPORTING REQUIREMENTS APPLY TO any staff member on the study team for a 
WFBCCC Institutional Interventional trial. Ultimately, the protocol PI has the primary 
responsibility for AE identification, documentation, grading and assignment of attribution 
to the investigational agent/intervention. However, when an AE event as described above 
is observed, it is the responsibility of the person who observed the event to be sure that it 
is reported to the DSMC. 
 
What is considered during protocol intervention? 
During protocol intervention is considered to be the time period while a patient is on study 
treatment or during the time period within 30 days of last study treatment (even if patient 
begins a new (non-study) treatment during the 30 days). This window of 30 days should be 
the standard window to be used in all protocols unless a specific scientific rationale is 
presented to suggest that a shorter window can be used to identify events. If it is a trial 
sponsored by Industry and the sponsor requires a longer window for monitoring of SAEs, 
then the longer window of time specified by the sponsor should be followed. 
 
 
 

 
Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
 
What is considered as an Unexpected Grade 4 event? 
Any grade 4 event that was not specifically listed as an expected adverse event in the 
protocol should be considered as unexpected. A grade 4 adverse event can be considered to 
be unexpected if it is an event that would not be expected based on the treatment being 
received or if it is unexpected based on the health of the patient. In either case, if there is 
any uncertainty about whether a grade 4 adverse event is expected or unexpected it should 
be reported to DSMC. 
 
DSMC notification responsibilities of the person (e.g., nurse) handling the 
reporting/documenting of the SAE in WISER: 
1. Make a phone call (or speak in person) to the appropriate clinical member of the 
DSMC according to the schedule as listed below (page if necessary). 
2. Enter a new SAE into the SAE module that is located in the Subject>> CRA Console in 
WISER WITHIN 24 HOURS of first knowledge of the event. Information can be 
entered and saved, but the DSMC members will not be notified until a date is 
entered into the  DSMC Notification Date Field. This will ensure that all persons that 
need to be made aware of the event (i.e., PI, study team members and DSMC 
members) will be notified; remember to file a copy of the confirmation. 
3. Document that the appropriate person(s) on the DSMC has been contacted. Indicate 
the name of the DSMC clinician that was contacted and the date and time contacted 
in the Event Narrative field in the SAE console of the particular subject. 
4. Document whether or not the protocol should be suspended based on the 
discussion with the DSMC clinician. This is the major function of the email 
notification. Enter whether the protocol should be suspended in the Event Narrative 
Field. 
5. Follow up/update the clinical member(s) of DSMC regarding any new developments 
or information obtained during the course of the SAE investigation and reporting 
process. 
 
Elements needed to complete the SAE form in the Subject Console in WISER (see Screen Shot 
3): 
1. Event Date 
2. Reported Date 
3. Reported by 
4. If Grade 5, enter Death Date 
5. If Grade 5, enter Death occurred: within 30 days 
6. Event Narrative: Brief description (include brief clinical history relevant to this event, 
including therapies believed related to event). Begin narrative with the DSMC clinician 
who was notified and Date/Time notified. In addition, state attribution by DSMC 
clinician as either “Unrelated”, “Unlikely”, “Possibly”, “Probably”, or “Definitely”.  
Always include the following here: 
i. DSMC clinician name, date/time contacted and comments 

 
Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
 
ii. Date of last dose before the event 
iii. Is suspension of the protocol needed? Y/N 
7. Treating Physician comments 
8. PI comments, if available 
9. Protocol Attribution after discussion with DSMC clinician 
10. Outcome (Fatal/Died, Intervention for AE Continues, Migrated AE, Not Recovered/Not 
Resolved, Recovered/Resolved with Sequelae, Recovered/Resolved without Sequelae, 
Recovering and Resolving) 
11. Consent form Change Required? Y/N 
12. SAE Classification *This is required in order for the email notification to be sent* 
13. Adverse Event Details – Enter all details for each AE associated with the SAE. 
a. Course start date 
b. Category 
c. AE Detail 
d. Comments 
e. Grade/Severity 
f. Unexpected Y/N 
g. DLT Y/N 
h. Attributions 
i. Action 
j. Therapy 
k. Click ADD to attach the AE Detail to the SAE. 
14. Enter Date Notified DSMC -- *This is required for the email notification to be sent* 
15. Click Submit. The auto-generated notification email will disseminate within 5 minutes. 
If you do not receive an email within 5 minutes, check that you have entered the 
“Date Notified DSMC” and the “SAE Classification”. If these have been entered and 
the email still has not been received, take a screen shot of the SAE in WISER and 
immediately email it out to all of the DSMC members listed in this SOP. In the subject 
line, indicate that this is a manual transmission of the SAE in lieu of the auto-
generated email. It is required that a notification goes to the DSMC members 
immediately so that their assessment can be obtained within the 24 hour period 
requirement. Contact the Cancer Center Programmer/Analyst to alert that there is an 
issue with the auto-generated email. 
 
The Clinical Members of DSMC to Notify by Phone or Page: 
 
Monday 
Tuesday 
Wednesday Thursday 
Friday 
Saturday Sunday 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu Seegars 

 
Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
 
 
  
 
 
 
 
 
 
 
Definition of Unavailable: 
As a general guideline if the first clinician that is contacted does not respond to the phone 
call or page within 30 minutes, then initiate contact with the next DSMC clinician listed in the 
table above on the particular day the SAE is being reported. Allow up to 30 minutes for the 
new DSMC clinician to respond to a phone call or page before contacting the next member in 
the table. These times (30 minutes) are a general guideline. Best judgment as a clinical 
research professional should be used giving considerations of the time of day, severity of the 
SAE, and other circumstances as to when it is appropriate to contact backup clinicians. If the 
event occurs near the end of day, then leave messages (voice or email) as appropriate and 
proceed with submitting the DSMC notification form. It is important to take reasonable steps 
and to document that some type of contact has been initiated to one or more of the clinical 
members of DSMC. 
 
DSMC CLINICAN RESPONSIBILITY: 
It is the responsibility of the DSMC clinician to review all reported events, evaluate the events 
as they are reported; and communicate a response to the Investigator, event reporter and 
the members of DSMC. The review will include but not be limited to the information 
reported; there may be times when additional information is needed in order for an 
assessment to be made and further communication directly with the investigator may be 
warranted. DSMC reserves the right to disagree with the Investigator's assessment. If DSMC 
does not agree with the Investigator, DSMC reserves the right to suspend the trial pending 
further investigation. If there is any immediate danger or harm that could be present for a 
future patient based on the information provided in the DSMC report then an immediate 
suspension of enrollment should be considered. 
 
AMENDMENTS TO PREVIOUS REPORTS 
If all pertinent information is unavailable with the initial submission, once the additional 
information is available do not submit a new report. Rather, go to the original email that 
was sent to the DSMC and using that email “reply to all”. Entitle this new email 
“Amendment for (list date of event and patient ID)” this will avoid duplications of the same 
event. List the additional information being reported. This information needs to be entered 
into WISER as well. To do this, go to the Subject console and click SAEs on the left column. 
Click on the appropriate SAE number that needs updating. Then click Update. This will allow 
additional  information to be added. 
 

 
Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
 
Acronyms 
AE – Adverse Event 
DSMC-Data and Safety Monitoring Committee 
SAE-Serious Adverse Event 
WFBCCC – Wake Forest Baptist Comprehensive Cancer Center 
NCI-National Cancer Institute 
WISER –Wake Integrated Solution for Enterprise Research 
 
Screen Shots: 
 
The following screen shots come from the SAE Console within the Subject Console in WISER. 
Screen Shot 1: 
 
Screen Shot 2:
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 57 of 83 
 
Screen Shot 3: 
 
 
 
Screen Shot 4: 
 
 
 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 58 of 83 
 
Appendix E – Adverse Event Log 
 
WFBCCC Adverse Event (AE) Log 
PI: _________________   Subject PID: 
________________ 
MRN: ________________ 
Cycle #: _________            Cycle Start Date: ____________      Cycle Start Time: ___________         Cycle End Date: ____________           Cycle End Time: ____________       
Adver
se 
Event 
CTC 
Term 
Lab 
Val
ue 
Gra
de       
(1-5) 
per 
CTC 
Sta
rt 
Dat
e 
En
d 
Dat
e 
Attribution 
DEF=Definite 
PROB=Prob
able 
POSS=Possi
ble 
UNLK=Unlik
ely 
UNRL=Unrel
ated 
Expect
ed 
N=No   
Y=Yes 
Serious 
Adverse Event 
Detail        
NO=No                 
LT=Life 
Threatening 
DTH=Death 
DIS=Disability 
HOS=Hospitaliz
ation           
CA=Caused 
congenital 
anomaly               
RI=Required 
intervention to 
prevent 
impairment  
Dose 
Limiti
ng 
Toxitit
y 
(DLT)     
N=No     
Y=Yes 
Action 
Taken 
NO=None         
DR=Dose 
Reduced 
RI=Regimen 
Interrupted       
TD=Therapy 
discontinued 
INTR=Interru
pted then 
reduced 
Therapy 
Given   
NO=None  
SYM=Sympto
matic  SUP= 
Supportive    
VSUP=Vigoro
us supportive 
Reportab
le?      
IRB-IRB      
STRC-
STRC          
FDA-FDA    
SPON-
Sponsor 
(Mark all 
that 
apply) 
Adver
se 
Event 
Repor
t 
(AER) 
Filed      
N=No   
Y=Yes 
Outcome  
R=Recove
red 
TX=Still 
under 
treatment/ 
observatio
n A=Alive 
with 
sequalae 
D=Died   
Treating 
MD 
Initials/D
ate 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Serious Adverse Event: Hospitalization; Disability; Birth Defect; Life-threatening; Death. 
CTCAE Version 4 - http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf 
DSMC- Data and Safety Monitoring Committee 
Version 1/10/18 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 59 of 83 
 
Appendix F - Patient Drug Diary  
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
Instructions: Complete the table below to track medication use.    
 
Was the full 7 days completed? Yes 
   No 
    
 
If No, was this due to side effects? Yes 
   No 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dose:  
75 mg 
   150 mg 
   300 mg
 
Side effects (including unusual 
symptoms),  
Date 
Day of one-
week 
schedule 
Taken  
__ __/__ __/__ __ 
1 
Yes 
   No 
    
 
__ __/__ __/__ __ 
2 
Yes 
   No 
    
 
__ __/__ __/__ __ 
3 
Yes 
   No 
    
 
__ __/__ __/__ __ 
4 
Yes 
   No 
    
 
__ __/__ __/__ __ 
5 
Yes 
   No 
    
 
__ __/__ __/__ __ 
6 
Yes 
   No 
    
 
__ __/__ __/__ __ 
7 
Yes 
   No 
    
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 60 of 83 
 
Appendix G – Fixed Dosing Patient Drug Diary  
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
Instructions: Complete the table below to track medication use.    
Dose:  
300 mg
 
Side effects (including unusual 
symptoms),  
Date 
Day of six-
week 
schedule 
Taken  
__ __/__ __/__ __ 
1 
Yes 
   No 
    
 
__ __/__ __/__ __ 
2 
Yes 
   No 
    
 
__ __/__ __/__ __ 
3 
Yes 
   No 
    
 
__ __/__ __/__ __ 
4 
Yes 
   No 
    
 
__ __/__ __/__ __ 
5 
Yes 
   No 
    
 
__ __/__ __/__ __ 
6 
Yes 
   No 
    
 
__ __/__ __/__ __ 
7 
Yes 
   No 
    
 
__ __/__ __/__ __ 
8 
Yes 
   No 
    
 
__ __/__ __/__ __ 
9 
Yes 
   No 
    
 
__ __/__ __/__ __ 
10 
Yes 
   No 
    
 
__ __/__ __/__ __ 
11 
Yes 
   No 
    
 
__ __/__ __/__ __ 
12 
Yes 
   No 
    
 
__ __/__ __/__ __ 
13 
Yes 
   No 
    
 
__ __/__ __/__ __ 
14 
Yes 
   No 
    
 
__ __/__ __/__ __ 
15 
Yes 
   No 
    
 
__ __/__ __/__ __ 
16 
Yes 
   No 
    
 
__ __/__ __/__ __ 
17 
Yes 
   No 
    
 
__ __/__ __/__ __ 
18 
Yes 
   No 
    
 
__ __/__ __/__ __ 
19 
Yes 
   No 
    
 
__ __/__ __/__ __ 
20 
Yes 
   No 
    
 
__ __/__ __/__ __ 
21 
Yes 
   No 
    
 
__ __/__ __/__ __ 
22 
Yes 
   No 
    
 
__ __/__ __/__ __ 
23 
Yes 
   No 
    
 
__ __/__ __/__ __ 
24 
Yes 
   No 
    
 
__ __/__ __/__ __ 
25 
Yes 
   No 
    
 
__ __/__ __/__ __ 
26 
Yes 
   No 
    
 
__ __/__ __/__ __ 
27 
Yes 
   No 
    
 
__ __/__ __/__ __ 
28 
Yes 
   No 
    
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in  
Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 61 of 83 
 
 
Was the full six weeks completed? Yes 
   No 
    
 
If No, was this due to side effects? Yes 
   No 
    
 
 
 
 
 
 
 
Dose:  
300 mg
 
Side effects (including unusual 
symptoms),  
Date 
Day of six-
week 
schedule 
Taken  
__ __/__ __/__ __ 
29 
Yes 
   No 
    
 
__ __/__ __/__ __ 
30 
Yes 
   No 
    
 
__ __/__ __/__ __ 
31 
Yes 
   No 
    
 
__ __/__ __/__ __ 
32 
Yes 
   No 
    
 
__ __/__ __/__ __ 
33 
Yes 
   No 
    
 
__ __/__ __/__ __ 
34 
Yes 
   No 
    
 
__ __/__ __/__ __ 
35 
Yes 
   No 
    
 
__ __/__ __/__ __ 
36 
Yes 
   No 
    
 
__ __/__ __/__ __ 
37 
Yes 
   No 
    
 
__ __/__ __/__ __ 
38 
Yes 
   No 
    
 
__ __/__ __/__ __ 
39 
Yes 
   No 
    
 
__ __/__ __/__ __ 
40 
Yes 
   No 
    
 
__ __/__ __/__ __ 
41 
Yes 
   No 
    
 
__ __/__ __/__ __ 
42 
Yes 
   No 
    
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 62 of 83 
 
 
Appendix H – Epworth Sleepiness Scale (ESS)  
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
Epworth Sleepiness Scale 
 
Name: 
Today’s date:   
 
 
 
 
How likely are you to doze off or fall asleep in the following situations, in contrast to feeling just tired? 
 
This refers to your usual way of life in recent times. 
 
Even if you haven’t done some of these things recently try to work out how they would have affected you. 
 
 
Use the following scale to choose the most appropriate number for each situation: 
 
0  =  would never doze 
1  =  slight chance of dozing 
2  =  moderate chance of dozing 
3  =  high chance of dozing 
 
It is important that you answer each question as best you can. 
 
Situation 
Chance of Dozing (0-3) 
 
 
Sitting and reading 
  
 
 
Watching TV 
  
 
 
Sitting, inactive in a public place (e.g. a theatre or a meeting) 
  
 
 
As a passenger in a car for an hour without a break 
  
 
 
Lying down to rest in the afternoon when circumstances permit     
 
 
Sitting and talking to someone     
 
 
Sitting quietly after a lunch without alcohol     
 
 
In a car, while stopped for a few minutes in the traffic    
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 63 of 83 
 
 
Appendix I – Pittsburgh Sleep Quality Index (PSQI)  
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
The Pittsburgh Sleep Quality Index (PSQI) is an effective instrument used to measure the quality and 
patterns of sleep in adults. It differentiates “poor” from “good” sleep quality by measuring seven areas 
(components): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep 
disturbances, use of sleeping medications, and daytime dysfunction over the last month. 
 
INSTRUCTIONS: 
The following questions relate to your usual sleep habits during the past month only. Your answers should 
indicate the most accurate reply for the majority of days and nights in the past month. Please answer all 
questions. 
During the past month, 
1. 
When have you usually gone to bed? 
 
 
 
 
____________ 
 
2. 
How long (in minutes) has it taken you to fall asleep each night? 
  
____________ 
 
3. 
What time have you usually gotten up in the morning? 
 
 
____________ 
 
4. 
A. How many hours of actual sleep did you get at night? 
 
 
____________ 
 
B.  How many hours were you in bed? 
 
 
 
 
____________ 
 
 5. During the past month, how often have you had trouble sleeping because you 
Not during 
the past 
month (0) 
Less than 
once a week 
(1) 
Once or 
twice a 
week (2) 
Three or more 
times a week 
(3) 
A.  Cannot get to sleep within 30 minutes 
B.  Wake up in the middle of the night or early morning 
C.  Have to get up to use the bathroom 
D.  Cannot breathe comfortably 
E.  Cough or snore loudly 
F.  Feel too cold 
G. Feel too hot 
H. Have bad dreams 
I.  Have pain 
J. Other reason (s), please describe, including how often you have had trouble sleeping because of this reason (s): 
6. During the past month, how often have you taken medicine (prescribed or “over the  counter”) to help you sleep? 
7. During the past month, how often have you had trouble staying awake while driving, eating meals, or engaging in 
social activity? 
8. During the past month, how much of a problem has it been for you to keep up enthusiasm to get things done? 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 64 of 83 
 
 
9.  During the past month, how would you rate your sleep quality overall? 
Very good 
(0) 
Fairly good 
(1) 
Fairly bad 
(2) 
Very bad (3) 
SCORING 
 
 
Component 1 
#9 Score 
C1   
 
Component 2 
#2 Score (<15min (0), 16-30min (1), 31-60 min (2), >60min (3)) 
+ #5a Score (if sum is equal 0=0; 1-2=1; 3-4=2; 5-6=3) 
C2   
 
Component 3 
#4 Score (>7(0), 6-7 (1), 5-6 (2), <5 (3) 
C3   
 
Component 4 
(total # of hours asleep) / (total # of hours in bed) x 100 
>85%=0, 75%-84%=!, 65%-74%=2, <65%=3 
C4   
 
Component 5 
# sum of scores 5b to 5j (0=0; 1-9=1; 10-18=2; 19-27=3) 
C5   
 
Component 6 
#6 Score 
C6   
 
Component 7 
#7 Score + #8 score (0=0; 1-2=1; 3-4=2; 5-6=3) 
C7   
 
 
 
Add the seven component scores together   ______________ 
 
 
Global PSQI     
 
 
 
______________ 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 65 of 83 
 
 
Appendix J – Brief Fatigue Inventory (BFI) 
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
 
Brief Fatigue Inventory 
 
Throughout our lives, most of us have times when we feel very tired or fatigued. Have you 
felt unusually tired or fatigued in the last week? 
   Yes 
   No 
 
1. Please rate your fatigue (weariness, tiredness) by circling the one number that best 
describes your fatigue right NOW. 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No fatigue 
 
 
 
 
 
 
 
As bad as you can 
imagine 
2. Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your 
USUAL level of fatigue during past 24 hours. 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No fatigue 
 
 
 
 
 
 
 
As bad as you can 
imagine 
3. Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your 
WORST level of fatigue during past 24 hours. 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No fatigue 
 
 
 
 
 
 
 
As bad as you can 
imagine 
4. Circle the one number that describes how, during the past 24 hours, fatigue has interfered with your: 
A. General activity 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
     Does not interfere 
 
 
 
 
 
Completely interferes 
 
B. Mood 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
     Does not interfere 
 
 
 
 
 
Completely interferes 
 
C. Walking ability 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
     Does not interfere 
 
 
 
 
 
Completely interferes 
 
D. Normal work (includes both work outside the home and daily chores) 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
     Does not interfere 
 
 
 
 
 
Completely interferes 
 
E. Relations with other people 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
     Does not interfere 
 
 
 
 
 
Completely interferes 
 
F. Enjoyment of life 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
     Does not interfere 
 
 
 
 
 
Completely interferes 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 66 of 83 
 
 
Appendix K – Cancer Fatigue Scale (CFS) 
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
The Cancer Fatigue Scale 
This questionnaire will ask you about any sense of fatigue you might be experiencing. For each ques- tion, 
please circle only one number you think most aptly describes your current state. Try to answer on the basis of 
first impressions, without thinking deeply about each question. 
 
Right now . . . 
No A little  Somewhat Considerably Very much 
 
1 Do you become tired easily? 
1 
2 
3 
4 
5 
2 Do you have the urge to lie down? 
1 
2 
3 
4 
5 
3 Do you feel exhausted? 
1 
2 
3 
4 
5 
4 Do you feel you have become 
careless? 
1 
2 
3 
4 
5 
5 Do you feel energetic? 
1 
2 
3 
4 
5 
6 Does your body felt heavy and tired? 
1 
2 
3 
4 
5 
7 Do you feel that you more often make 
errors while speaking? 
1 
2 
3 
4 
5 
8 Do you feel interest in anything? 
1 
2 
3 
4 
5 
9 Do you feel fed-up? 
1 
2 
3 
4 
5 
10 Do you feel you have become 
forgetful? 
1 
2 
3 
4 
5 
11 Can you concentrate on certain things? 
1 
2 
3 
4 
5 
12 Do you feel reluctant? 
1 
2 
3 
4 
5 
13 Do you feel that your thinking has 
become slower? 
1 
2 
3 
4 
5 
14 Can you encourage yourself to do 
anything? 
1 
2 
3 
4 
5 
15 Do you feel such fatigue that you don’t 
know what to do with yourself? 
1 
2 
3 
4 
5 
 
The Calculation Method 
 
 
Factor 1 = (items 1 + 2 + 3 + 6 + 9 + 12 + 15) - 7 
P. 
(Physical subscale) 
Factor 2 = 20 - (items 5 + 8 + 11 + 14) 
P. 
(Affective subscale) 
Factor 3 = (items 4 + 7 + 10 + 13) - 4 
P. 
(Cognitive subscale) 
Add the factors together 
P. 
(Total scale score) 
*Subtractions adjust for 0 as a state of no fatigue. 
 
 
 
 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 67 of 83 
 
 
Appendix L – Beck Depression Inventory  
 
The questionnaire consists of 21 groups of statements. After reading each group of statements 
carefully check the box next to the one statement in each group which best describes the way you 
have been feeling in the past week, including today. If several statements within a group seem to 
apply equally well, check each one. Be sure to read all the statements in each group before making 
your choices. 
 
1.  
□ I do not feel sad. 
□ I feel sad. 
□ I am sad all the time and can’t snap out of it. 
□ I am so sad or unhappy that I can’t stand it. 
 
2.  
□ I am not particularly discouraged about the future. 
 
□ I feel discouraged about the future. 
 
□ I feel I have nothing to look forward to. 
 
□ I feel that the future is hopeless and that things cannot improve. 
 
3.  
□ I do not feel like a failure. 
 
□ I feel I have failed more than the average person. 
 
□ As I look back on my life, all I can see is a lot of failures. 
 
□ I feel I am a complete failure as a person. 
 
4.  
□ I get as much satisfaction out of things as I used to. 
 
□ I don’t enjoy things the way I used to. 
 
□ I don’t get real satisfaction out of anything anymore.  
 
□ I am dissatisfied or bored with everything. 
 
5.  
□ I don’t feel particularly guilty. 
 
□ I feel guilty a good part of the time. 
 
□ I feel quite guilty most of the time. 
 
□ I feel guilty all of the time. 
 
6.  
□ I don’t feel I am being punished. 
 
□ I feel I may be punished. 
 
□ I expect to be punished. 
 
□ I feel I am being punished. 
 
7.  
□ I don’t feel disappointed in myself. 
 
□ I am disappointed in myself. 
 
□ I am disgusted with myself. 
 
□ I hate myself. 
 
8.  
□ I don’t feel I am any worse than anybody else. 
 
□ I am critical of myself for my weaknesses or mistakes. 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 68 of 83 
 
 
 
□ I blame myself all the time for my faults. 
 
□ I blame myself for everything bad that happens. 
 
9.  
□ I don’t have any thoughts of killing myself. 
 
□ I have thoughts of killing myself, but I would not carry them out. 
 
□ I would like to kill myself. 
 
□ I would kill myself if I had the chance. 
 
10.  
□ I don’t cry any more than usual. 
 
□ I cry more now than I used to. 
 
□ I cry all the time now. 
 
□ I used to be able to cry, but now I can’t cry even though I want to. 
 
11.  
□ I am no more irritated now than I ever am. 
 
□ I get annoyed or irritated more easily than I used to. 
 
□ I feel irritated all the time now. 
 
□ I don’t get irritated at all by the things that used to irritate me. 
 
12.  
□ I have not lost interest in other people. 
 
□ I am less interested in other people than I used to be. 
 
□ I have lost most of my interest in other people. 
 
□ I have lost all of my interest in other people. 
 
13.  
□ I make decisions about as well as I ever could. 
 
□ I put off making decisions more than I used to. 
 
□ I have greater difficulty in making decisions than before. 
 
□ I can’t make decisions at all anymore. 
 
14.  
□ I don’t feel I look any worse than I used to. 
 
□ I am worried that I am looking old or unattractive. 
 
□ I feel that there are permanent changes in my appearance  
 
□ I believe that I look ugly. 
 
15.  
□ I can work about as well as before. 
 
□ It takes an extra effort to get started at doing something. 
 
□ I have to push myself very hard to do anything. 
 
□ I can’t do any work at all. 
 
16.  
□ I can sleep as well as usual. 
 
□ I don’t sleep as well as I used to. 
 
□ I wake up 1-2 hours earlier than usual and find it hard to get back to sleep. 
 
□ I wake up several hours earlier than I used to and cannot get back to sleep. 
 
17.  
□ I don’t get more tired than usual. 
 
□ I get tired more easily than I used to. 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 69 of 83 
 
 
 
□ I get tired from doing almost anything. 
 
□ I am too tired to do anything. 
 
 
 
18.  
□ My appetite is no worse than usual. 
 
□ My appetite is not as good as it used to be. 
 
□ My appetite is much worse now. 
 
□ I have no appetite at all anymore. 
 
19.  
□ I haven’t lost much weight, if any, lately. 
 
□ I have lost more than 5 pounds. 
 
□ I have lost more than 10 pounds. 
 
□ I have lost more than 15 pounds. 
 
I am purposefully trying to lose weight by eating less:  
□ Yes  
□ No 
 
20.  
□ I am no more worried about my health than usual. 
 
□ I am worried about physical problems like aches/pains, upset stomach, or constipation. 
 
□ I am very worried about physical problems and it’s hard to think of much else. 
 
□ I am so worried about my physical problems that I cannot think about anything else. 
 
21.  
□ I have not noticed any recent change in my interest in sex. 
 
□ I am less interested in sex than I used to be. 
 
□ I am much less interested in sex now. 
 
□ I have lost interest in sex completely. 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 70 of 83 
 
 
 Appendix M – Neurocognitive Battery Record 
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator: Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
Instructions: Complete the table below to track date of neurocognitive testing and assessments performed.  
 
V1 Test Date: 
Test Name: 
Completed: 
If not completed, state 
reason 
__ __/__ __/__ __ 
Digit Span (DS) 
Yes 
   No 
    
 
Letter Number 
Sequencing (LNS) 
Yes 
   No 
    
 
Matrix Reasoning (MR) 
Yes 
   No 
    
 
Symbol Search (SS) 
Yes 
   No 
    
 
Coding (CD) 
Yes 
   No 
    
 
Controlled Oral Word 
Association Test 
(COWAT) 
Yes 
   No 
    
 
Trail Making Test Parts 
A and B (TMT A & B) 
Yes 
   No 
    
 
Montreal Cognitive 
Assessment (MoCA) 
Yes 
   No 
    
 
Total Score 
 
 
 
   
V3 Test Date: 
Test Name: 
Completed: 
If not completed, state 
reason 
__ __/__ __/__ __ 
Digit Span (DS) 
Yes 
   No 
    
 
Letter Number 
Sequencing (LNS) 
Yes 
   No 
    
 
Matrix Reasoning (MR) 
Yes 
   No 
    
 
Symbol Search (SS) 
Yes 
   No 
    
 
Coding (CD) 
Yes 
   No 
    
 
Controlled Oral Word 
Association Test 
(COWAT) 
Yes 
   No 
    
 
Trail Making Test Parts 
A and B (TMT A & B) 
Yes 
   No 
    
 
Montreal Cognitive 
Assessment (MoCA) 
Yes 
   No 
    
 
Total Score 
 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 71 of 83 
 
 
Appendix N – FACT Br (Version 4) 
 
 
 
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator:, Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
Below is a list of statements that other people with your illness have said are important. Please circle or 
mark one number per line to indicate your response as it applies to the past 7 days. 
 
PHYSICAL WELL-BEING 
Not 
at all 
A little 
bit 
Some- 
what 
Quite 
a bit 
Very 
much 
GP1 
I have a lack of energy...................................................... 
0 
1 
2 
3 
4 
GP2 
I have nausea..................................................................... 
0 
1 
2 
3 
4 
GP3 
Because of my physical condition, I have trouble 
meeting the needs of my family........................................ 
0 
1 
2 
3 
4 
GP4 
I have pain......................................................................... 
0 
1 
2 
3 
4 
GP5 
I am bothered by side effects of treatment........................ 
0 
1 
2 
3 
4 
GP6 
I feel ill.............................................................................. 
0 
1 
2 
3 
4 
GP7 
I am forced to spend time in bed ...................................... 
0 
1 
2 
3 
4 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 72 of 83 
 
 
SOCIAL/FAMILY WELL-BEING 
Not 
at all 
A little 
bit 
Some- 
what 
Quite 
a bit 
Very 
much 
GS1 
I feel close to my friends .................................................. 
0 
1 
2 
3 
4 
GS2 
I get emotional support from my family........................... 
0 
1 
2 
3 
4 
GS3 
I get support from my friends ........................................... 
0 
1 
2 
3 
4 
GS4 
My family has accepted my illness................................... 
0 
1 
2 
3 
4 
GS5 
I am satisfied with family communication about my 
illness ................................................................................ 
0 
1 
2 
3 
4 
GS6 
I feel close to my partner (or the person who is my 
main support) .................................................................... 
0 
1 
2 
3 
4 
Q1 
Regardless of your current level of sexual activity, please 
answer the following question. If you prefer not to answer 
it, please check this box 
and go to the next section. 
GS7 
I am satisfied with my sex life .......................................... 
0 
1 
2 
3 
4 
 
 
By circling one (1) number per line, please indicate how true each statement has been for you during the 
past 7 days 
 
EMOTIONAL WELL-BEING 
Not 
at all 
A little 
bit 
Some- 
what 
Quite 
a bit 
Very 
much 
GE1 
I feel sad............................................................................ 
0 
1 
2 
3 
4 
GE2 
I am satisfied with how I am coping with my illness ....... 
0 
1 
2 
3 
4 
GE3 
I am losing hope in the fight against my illness ............... 
0 
1 
2 
3 
4 
GE4 
I feel nervous .................................................................... 
0 
1 
2 
3 
4 
GE5 
I worry about dying .......................................................... 
0 
1 
2 
3 
4 
GE6 
I worry that my condition will get worse.......................... 
0 
1 
2 
3 
4 
 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 73 of 83 
 
 
FUNCTIONAL WELL-BEING 
Not 
at all 
A little 
bit 
Some- 
what 
Quite 
a bit 
Very 
much 
GF1 
I am able to work (include work at home)........................ 
0 
1 
2 
3 
4 
GF2 
My work (include work at home) is fulfilling .................. 
0 
1 
2 
3 
4 
GF3 
I am able to enjoy life ....................................................... 
0 
1 
2 
3 
4 
GF4 
I have accepted my illness ................................................ 
0 
1 
2 
3 
4 
GF5 
I am sleeping well ............................................................. 
0 
1 
2 
3 
4 
GF6 
I am enjoying the things I usually do for fun.................... 
0 
1 
2 
3 
4 
GF7 
I am content with the quality of my life right now ........... 
0 
1 
2 
3 
4 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 74 of 83 
 
 
By circling one (1) number per line, please indicate how true each statement has been for you 
during the past 7 days. 
 
 
ADDITIONAL CONCERNS 
Not at all 
A little 
bit 
Some- 
what 
Quite a 
bit 
Very 
much 
I am able to concentrate.................................................... 
0 
1 
2 
3 
4 
I have had seizures (convulsions) ..................................... 
0 
1 
2 
3 
4 
I can remember new things............................................... 
0 
1 
2 
3 
4 
I get frustrated that I cannot do things I used to ............... 
0 
1 
2 
3 
4 
I am afraid of having a seizure (convulsion) .................... 
0 
1 
2 
3 
4 
I have trouble with my eyesight........................................ 
0 
1 
2 
3 
4 
I feel independent ............................................................. 
0 
1 
2 
3 
4 
I have trouble hearing ....................................................... 
0 
1 
2 
3 
4 
I am able to find the right word(s) to say what I mean..... 
0 
1 
2 
3 
4 
I have difficulty expressing my thoughts.......................... 
0 
1 
2 
3 
4 
I am bothered by the change in my personality................ 
0 
1 
2 
3 
4 
I am able to make decisions and take responsibility......... 
0 
1 
2 
3 
4 
I am bothered by the drop in my contribution to the 
family ................................................................................ 
0 
1 
2 
3 
4 
I am able to put my thoughts together .............................. 
0 
1 
2 
3 
4 
I need help in caring for myself (bathing, dressing, 
eating, etc.)........................................................................ 
0 
1 
2 
3 
4 
I am able to put my thoughts into action .......................... 
0 
1 
2 
3 
4 
I am able to read like I used to.......................................... 
0 
1 
2 
3 
4 
I am able to write like I used to ........................................ 
0 
1 
2 
3 
4 
I am able to drive a vehicle (my car, truck, etc.) .............. 
0 
1 
2 
3 
4 
I have trouble feeling sensations in my arms, hands, or 
legs.................................................................................... 
0 
1 
2 
3 
4 
I have weakness in my arms or legs ................................. 
0 
1 
2 
3 
4 
I have trouble with coordination....................................... 
0 
1 
2 
3 
4 
Br1 
Br2 
Br3 
Br4 
Br5 
Br6 
Br7 
NTX 
6 
Br8 
Br9 
Br10 
Br11 
Br12 
Br13 
Br14 
Br15 
Br16 
Br17 
Br18 
Br19 
Br20 
Br21 
An 
10 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 75 of 83 
 
 
I get headaches.................................................................. 
0 
1 
2 
3 
4 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 76 of 83 
 
 
Appendix O – Concurrent Medications Form 
 
Study Number: ___ ___ ___ ___ ___ 
 PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
 
PI: Roy Strowd, M.D. _________________________________ 
 Date (mm/dd/yyyy): ___ ___/___ ___/___ ___ ___ ___ 
 
 
Instructions: Fill this form out at the baseline/pre-study visit and/or additional visits per protocol. 
 
Study Visit (if needed per protocol):  
 Baseline 
 Visit  1 
 Visit  2 
 Visit  3 
 Other visit: (please specify) ________________ 
Current Medications List 
Prescription Medications: 
 
Name of Medication 
Dose 
Units 
Frequency  Condition 
Medication 
Taken For 
Start date 
(mm/dd/yy) 
Stop date 
(mm/dd/yy) 
Formulation 
Route 
Notes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 77 of 83 
 
 
Appendix P – Off-Study Form  
 
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator:, Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
Instructions: Complete this form if the patient either withdraws consent or is removed from the study.  
 
Name of Person Competing form_____________________________ 
 
Did the subject meet eligibility criteria for study enrollment?   Yes 
   No 
 
 
Was the subject removed from the study per physician decision?  Yes 
   No 
  
(if yes, move to #5) 
 
Did the patient withdraw consent to participate in the study?  Yes 
   No 
  
(if yes move to #1) 
 
Reason for patient withdrawal: 
1. 
 Unacceptable toxicity from solriamfetol 
2. 
 Did not want to participate anymore. Reason: 
____________________________________________________________________ 
3. 
Other: ____________________________________ 
4. Please specify what portion of the study the subject wishes to withdraw from: 
 
 
 
 For just the solriamfetol administration only 
 For all components of the research study (including follow up in the medical record)  
 
Reason(s) for Removal:  
5. 
 Patient exhibited progression of disease 
 
6. 
 Unacceptable toxicity from solriamfetol 
 
7. 
 Investigator’s discretion to withdraw patient from the study because continued participation in the 
study is not in the patient’s best interest (*Describe below) 
 
8. 
 Undercurrent illness: a condition, injury, or disease unrelated to the intended disease for which 
the study is investigating, that renders continuing the treatment unsafe or regular follow-up 
impossible (*Describe below) 
 
9. 
 General or specific changes in the patient’s condition that renders the patient ineligible for further 
investigational treatment (*Describe below) 
 
10. 
 Non-compliance with investigational treatment, protocol-required evaluations or follow-up visits 
(*Describe below) 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 78 of 83 
 
 
11. 
 Termination of the clinical trial by the clinical sponsor 
 
Comment: 
 
If reason for withdrawal includes #7, 8, 9, or 10 then please add comments clarifying this 
information)____________________________________________________________________________
______________________________________________________________________________________
______________________________________________________________________________________
______________________________________________ 
 
 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 79 of 83 
 
 
Appendix Q – MR Imaging Record  
 
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator:, Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
 
Instructions: Complete the table below to track date of MRI Brain throughout the study. 
 
Date of Enrollment: __ __/__ __/__ __ 
 
Off Study Date: __ __/__ __/__ __ 
 
Please record the date of any MR imaging between the date of enrollment and off study dates. If there is no 
imaging in between these times, please record the date of the next MR imaging after the off study date. If 
there is no imaging available, please list the reason.   
 
 
Date of 
neuroimaging 
 
Completed: 
If not completed, state reason 
 
__ __/__ __/__ __ 
 
Yes 
   No 
    
 
 
__ __/__ __/__ __ 
 
Yes 
   No 
    
 
 
__ __/__ __/__ __ 
 
Yes 
   No 
    
 
 
__ __/__ __/__ __ 
 
Yes 
   No 
    
 
 
__ __/__ __/__ __ 
 
Yes 
   No 
    
 
 
__ __/__ __/__ __ 
 
Yes 
   No 
    
 
 
__ __/__ __/__ __ 
 
Yes 
   No 
    
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 80 of 83 
 
 
Appendix R – Sleep Diary and Actigraphy Record 
Week of ______ 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6  
Day 7 
 Actigraph worn? 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
Did you take a nap? 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
How long did you nap? 
  
  
  
  
  
  
  
Time you fell asleep: 
AM/PM 
  
  
  
  
  
  
Time you woke up: 
AM/PM 
  
  
  
  
  
  
Did you take anything to 
help you sleep at night? 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
□ Yes   □ No 
If so, indicate amount:  
  
  
  
  
  
  
  
Prescribed medicine 
  
  
  
  
  
  
  
Over-the-counter 
  
  
  
  
  
  
  
Alcohol    
  
  
  
  
  
  
Time you entered bed? 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
Minutes/hours it took you 
to fall asleep? 
  
  
  
  
  
  
  
Number of times you 
awoke during the night? 
  
  
  
  
  
  
  
Time it took you to fall 
back asleep: 
  
  
  
  
  
  
  
First awakening 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
Second awakening 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
Third awakening 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
Fourth awakening 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
Fifth awakening 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
Sixth awakening  
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
HR      MIN 
Indicate time you woke 
up: 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
Indicate time you got out 
of bed: 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
Falling asleep last night 
was:  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
Staying asleep last night 
was: 
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
Rate the quality of sleep 
for this night:  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
Rate your sleep this night 
compared to other nights: 
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Extremely 
difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Difficult  
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 
 □ Fair 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 81 of 83 
 
 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
 □ Very Easy 
Appendix S – Glioma History 
 
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator:, Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
Oncologic history 
 
a) Glioma histologic diagnosis  
a.  Astrocytoma 
b.  Oligodendroglioma 
c.  Glioblastoma 
d.  Other: _____________________________ 
 
b) WHO Grade of glioma:  WHO Grade 2    WHO Grade 3    WHO Grade 4 
 
c) Molecular data (e.g. IDH, MGMT, 1p19q) 
 
 
 
Other Medical Conditions/Diagnoses (list all):  _______________________________________ 
 
____________________________________________________________________________ 
 
____________________________________________________________________________ 
Molecular Features of the Primary Brain Tumor: 
 
MGMT promoter methylation status 
 Methylated 
 Not methylated 
 Not reported 
IDH mutational status 
 IDH1 mutated 
 IDH2 mutated 
 IDH1 and IDH2 wild type 
 IDH1 and IDH2 testing not reported 
1p/19q deletion status 
 1p19q codeleted 
 1p deletion only 
 19q deletion only 
 1p19q NOT codeleted (normal) 
 1p and 19q deletion not reported 
 
 
Treatment Summary: 
 
 
Treatment 
 
Completed: 
 
Date of Treatment(s) 
 
Notes 
Radiation 
Yes 
   No 
    
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 82 of 83 
 
 
Therapy 
RT start date: __ __/__ __/__ __ 
 
RT end date: __ __/__ __/__ __ 
 
Concurrent 
Chemotherapy 
Yes 
   No 
    
 
Name of chemotherapy: 
 
_______________________ 
 
 
Adjuvant 
Chemotherapy 
Yes 
   No 
    
 
Name of chemotherapy: 
 
_______________________ 
 
 
 
 
Recurrence Information: 
 
 
Recurrence 
Number 
 
Recurrence (y/n): 
 
Date of Recurrence 
 
Treatment 
First Recurrence 
Yes 
   No 
    
 
__ __/__ __/__ __ 
 
 
Second Recurrence 
Yes 
   No 
    
 
__ __/__ __/__ __ 
 
 
Third Recurrence 
Yes 
   No 
    
 
__ __/__ __/__ __ 
 
 
Fourth Recurrence 
Yes 
   No 
    
 
__ __/__ __/__ __ 
 
 
Fifth Recurrence 
Yes 
   No 
    
 
__ __/__ __/__ __ 
 
 
 
 
 
 
 
 

Open Label Safety Study of Solriamfetol to Promote Wakefulness and Improve Cognition and Quality of Life in Patients with Primary 
Gliomas  
Wake Forest Baptist Comprehensive Cancer Center 
WFBCCC 98418 
 
Protocol version date 05/19/21 
 
 
 
                                              Page 83 of 83 
 
 
Appendix T – Telephone Script 
 
 
Study Number: __ __ __ __ __ 
PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
Investigator:, Roy Strowd, M.D. 
Date: __ __/__ __/__ __ 
 
Hello, my name is {TBD - Project Coordinator} and I am calling on behalf of {Wake Forest Baptist Medical 
Center}.  May I please speak with {SUBJECT’S NAME}? 
 
I am going to ask you several questions about any side effects that you have experienced in the last week. 
When answering these questions, I would like for you to think only about symptoms that you have had over 
the last 1 week. We will focus on the period of time that you have been on the current dose of the 
solriamfetol drug that is a part of this study. 
 
Over the last 1 week, have you had any side effects from solriamfetol (the study drug)?   Yes   No 
 
Over the last 1 week, have you had any of the following symptoms (and if so, please describe them)? 
 Headache 
 
_______________________________________________ 
 Nausea 
 
_______________________________________________ 
 Decreased appetite  
_________________________________________ 
 Anxiety 
 
_______________________________________________ 
 Diarrhea 
 
_______________________________________________ 
 Dry mouth 
 
_______________________________________________ 
 Insomnia 
 
_______________________________________________ 
 Chest pain 
 
_______________________________________________ 
 New shortness of breath 
 
___________________________________ 
 Other   
 
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