Methylphenidate in Treating Patients With Fatigue Caused by Cancer

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00376675
• Collaborator: National Cancer Institute (NCI) (NIH), McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc. (Industry)
• Enrollment: 148
• Locations: 238
• Arms: 2
• Duration (Months): 28
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Methylphenidate may help relieve fatigue caused by cancer. It is not yet known whether methylphenidate is more effective than a placebo in relieving fatigue and improving quality of life in patients with cancer.

PURPOSE: This randomized phase III trial is studying methylphenidate to see how well it works in treating patients with fatigue caused by cancer.

Condition or Disease	Intervention/Treatment	Phase
Fatigue; Unspecified Adult Solid Tumor, Protocol Specific	Drug: methylphenidate hydrochloride; Other: placebo	Phase 3

Detailed Description

OBJECTIVES:

Primary

• Test the efficacy of long-acting methylphenidate in patients with cancer-related fatigue as measured using an item of the Brief Fatigue Inventory.

Secondary

• Evaluate the tolerability and adverse events associated with this drug in these patients.

• Study the effect of this drug on quality of life (QOL)-related variables (vitality, sleep quality, overall QOL, QOL domains, other fatigue measures, and perceived treatment efficacy) in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease stage (0, I, or II vs III or IV), level of fatigue at baseline (4-7 vs 8-10), concurrent biological therapy (yes vs no), concurrent chemotherapy (yes vs no), and concurrent radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral methylphenidate daily on days 1-28.

• Arm II: Patients receive oral placebo daily on days 1-28.

Patients in both arms complete questionnaires to assess their symptoms of fatigue, overall mood, quality of life, sleep quality, and adverse effects from treatment at baseline and once weekly for 4 weeks. Patients also complete a Symptom Experience Diary.

McNeil Consumer & Specialty Pharmaceuticals provided medication support for NCCTG N05C7.

PROJECTED ACCRUAL: A total of 140 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 148 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Long Acting Methylphenidate (Concerta™) for Cancer-Related Fatigue: A Phase III, Randomized, Double-Blind Placebo Controlled Study
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral methylphenidate hydrochloride daily on days 1-28.	Drug: methylphenidate hydrochloride; Given orally
Placebo Comparator: Arm II Patients receive oral placebo daily on days 1-28.	Other: placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. Prorated AUC of Total Fatigue as Measured by the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 [Baseline to week 4]

   The prorated area under the curve (AUC) for the usual fatigue question of the BFI at baseline and at weeks 1-4 after being translated onto a 0 (poor quality of life (QOL) or bad symptoms) to 100 (best QOL or no symptoms) point scale was calculated as the following: For those completed 4 weeks item: AUC/4; For those completed up to week 3 item: (AUC * 4) / 3; For those completed up to week 2 item: AUC * 2; For those completed up to week 1 item: AUC * 4; The prorated AUC scores were then transformed onto 0 to 100 point scale with 0 (poor QOL or bad symptoms) and 100 (best QOL or no symptoms) for analysis.

Secondary Outcome Measures

1. Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 [Baseline and Week 4]

   The Symptom Experience Diary (SED) consists of 12 items. All scores were translated onto a 0-100 point scale, with 0 represent poor quality of life (QOL) or bad symptom and 100 is best QOL or no symptoms.The change in severity of adverse events was calculated as subtracting the item scores at baseline from the scores at week 4.

2. AUC of Sleep Quality as Measured by the Pittsburgh Sleep Quality Index at Baseline and at Weeks 1-4 [Baseline to Week 4]

   Pittsburgh Sleep Quality Index (PSQI) consists of 19 items and 7 scales. The AUC for the overall PSQI at baseline and at weeks 1-4 after being translated onto a 0 to 100 point scale was calculated. Higher scores are better.

3. AUC of Vitality as Measured by the Short Form-36 Vitality Subscale at Baseline and at Weeks 1-4 [Baseline to Week 4]

   The SF-36 is a 36-item short form to measure health status in various populations. The vitality subscale is comprised of 4 items and is a measure of energy level as well as fatigue. The AUC for the vitality subscale at baseline and at weeks 1-4 after being translated onto a 0 to 100 point scale was calculated. Higher scores are better.

4. AUC of Overall Quality of Life (QOL) and QOL Domains as Measured by the Linear Analogue Self Assessment at Baseline and at Weeks 1-4 [Baseline to Week 4]

   Linear Analogue Self Assessment (LASA) consists of 6 single-item numeric analogue scales. The AUC for the six-items at baseline and at weeks 1-4 after being translated onto a 0 to 100 point scale was calculated. Higher scores are better.

5. AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 [Baseline to Week 4]

   Area under the curve (AUC) for the other fatigue items of the BFI at baseline and at weeks 1-4 after being translated onto a 0 to 100 point scale was calculated. Higher scores are better.

6. Anchor-based Minimally Important Difference in SGIC Overall Quality of Life Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue [Baseline and Week 4]

   Perceived treatment efficacy was measured by the Subject Global Impression of Change (SGIC). The SGIC is a 3-point item in which the patient rates the change in the overall status since beginning the study drug (ranging from very much better, moderately better, a little better, about the same, a little worse, moderately worse, to very much worse). The average change in patient fatigue scores for those participants who express a perceived change of "a little better" via the SGIC scores were calculated. BFI usual fatigue item score was translated into 0 to 100 point scale for the analysis, with 0 (poor QOL or bad symptoms) and 100 (best QOL or no symptoms).

7. Anchor-based Minimally Important Difference in SGIC Physical Condition Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue [Baseline and Week 4]

   Perceived treatment efficacy was measured by the Subject Global Impression of Change (SGIC). The SGIC is a 3-point item in which the patient rates the change in the overall status since beginning the study drug (ranging from very much better, moderately better, a little better, about the same, a little worse, moderately worse, to very much worse). The average change in patient fatigue scores for those participants who express a perceived change of "a little better" via the SGIC scores were calculated. BFI usual fatigue item score was translated into 0 to 100 point scale for the analysis, with 0 (poor QOL or bad symptoms) and 100 (best QOL or no symptoms).

8. Anchor-based Minimally Important Difference in SGIC Emotional State Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue [Baseline and Week 4]

   Perceived treatment efficacy was measured by the Subject Global Impression of Change (SGIC). The SGIC is a 3-point item in which the patient rates the change in the overall status since beginning the study drug (ranging from very much better, moderately better, a little better, about the same, a little worse, moderately worse, to very much worse). The average change in patient fatigue scores for those participants who express a perceived change of "a little better" via the SGIC scores were calculated. BFI usual fatigue item score was translated into 0 to 100 point scale for the analysis, with 0 (poor QOL or bad symptoms) and 100 (best QOL or no symptoms).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. ≥ 18 years of age

2. Men or women with a history of cancer-related fatigue as defined by a score ≥ 4 on a fatigue numerical analogue scale (0 - 10)

3. Fatigue for ≥ 1 month prior to registration

4. ECOG Performance Score (PS) 0, 1, or 2

5. Life expectancy ≥ 6 months

6. Histologic or cytologic proven cancer other than brain cancer or CNS lymphoma

7. Laboratory values obtained ≤ 30 days prior to registration:

• Hgb ≥ 10 g/dL

1. Willing and able to provide informed consent

2. Negative pregnancy test (urine or serum) done ≤ 7 days prior to registration, for women of childbearing potential only

3. Ability to complete questionnaire(s) by themselves or with assistance

4. Biological therapy (i.e. immunotherapy, biotherapy), chemotherapy or radiation therapy will be allowed

5. Use of a stable dose of anti-depressants (except tricyclic anti-depressants) will be allowed

6. Erythropoietic agents to treat anemia, and steroids as a part of cancer treatment and for symptom management (except for fatigue) will be allowed

Exclusion Criteria:

1. Hypersensitivity to methylphenidate

2. Any prior use of methylphenidate

3. Concomitant (≤ 2 weeks) use of prescription stimulants (pemoline, modafinil, amphetamines); other medications, herbal products or dietary supplements for fatigue

4. Uncontrolled hypertension [defined as systolic blood pressure (BP) ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg on 2 separate visits ≤ 2 months prior to randomization]; or a resting heart rate > 100

5. Moderate or severe pain as defined by an average daily score ≥ 4 on a pain analog scale (0 - 10)

6. Known brain metastasis or primary CNS malignancy

7. Clinically significant acute or chronic progressive or unstable neurologic (dementia, delirium, or seizure disorder), hepatic, renal, cardiovascular, thyroid, or respiratory disease that would limit participation in the study per MD discretion or judgment

8. Psychiatric disorder such as manic depression, anxiety disorder, bipolar disorder, obsessive compulsive disorder, or schizophrenia

9. Major surgery < 4 weeks prior to registration. (Note: Insertion of central venous catheter is not considered major surgery.)

10. Using a drug contraindicated when taken concurrently with methylphenidate: coumarin anticoagulants, anticonvulsants, tricyclic antidepressants, antipsychotics, monoamine oxidase inhibitors, clonidine, theophylline, and pseudoephedrine

Note: use of Compazine prescribed as an antiemetic is permitted for use while participating in this study.

1. Additional medical conditions where use of methylphenidate is contraindicated:

glaucoma, motor tics, family history or diagnosis of Tourette's syndrome, history of drug or alcohol abuse or intestinal obstruction.

1. Pregnant women or nursing women. Women of childbearing potential who are unwilling to employ adequate contraception. This study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown.

2. Untreated hypothyroidism (TSH ≥ 5)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
3	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
4	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
5	St. Anthony Central Hospital	Denver	Colorado	United States	80204
6	Porter Adventist Hospital	Denver	Colorado	United States	80210
7	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
8	St. Joseph Hospital	Denver	Colorado	United States	80218
9	Rose Medical Center	Denver	Colorado	United States	80220
10	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80224-2522
11	Swedish Medical Center	Englewood	Colorado	United States	80110
12	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502
13	North Colorado Medical Center	Greeley	Colorado	United States	80631
14	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
15	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80502
16	McKee Medical Center	Loveland	Colorado	United States	80539
17	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
18	North Suburban Medical Center	Thornton	Colorado	United States	80229
19	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
20	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
21	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912
22	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
23	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
24	Graham Hospital	Canton	Illinois	United States	61520
25	Memorial Hospital	Carthage	Illinois	United States	62321
26	Eureka Community Hospital	Eureka	Illinois	United States	61530
27	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
28	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
29	Mason District Hospital	Havana	Illinois	United States	62644
30	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
31	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
32	McDonough District Hospital	Macomb	Illinois	United States	61455
33	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
34		Moline	Illinois	United States	61265
35	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
36	Community Cancer Center	Normal	Illinois	United States	61761
37	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
38	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
39	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
40	Proctor Hospital	Peoria	Illinois	United States	61614
41	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
42	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
43	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
44	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
45	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
46	Perry Memorial Hospital	Princeton	Illinois	United States	61356
47	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
48	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
49	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
50	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
51	Elkhart General Hospital	Elkhart	Indiana	United States	46515
52	Howard Community Hospital	Kokomo	Indiana	United States	46904
53	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
54	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
55	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
56	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
57	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
58	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
59	McFarland Clinic, PC	Ames	Iowa	United States	50010
60		Bettendorf	Iowa	United States	52722
61	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
62	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
63	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
64	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
65	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
66	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
67	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
68	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
69	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
70	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
71	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
72	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
73	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
74	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
75	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
76	Southwest Medical Center	Liberal	Kansas	United States	67901
77	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
78	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
79	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
80	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
81	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
82	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
83	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
84	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
85	CCOP - Wichita	Wichita	Kansas	United States	67214
86	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
87	Wesley Medical Center	Wichita	Kansas	United States	67214
88	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
89	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
90	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
91	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
92	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
93	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
94	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
95	Hurley Medical Center	Flint	Michigan	United States	48503
96	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
97	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
98	Foote Memorial Hospital	Jackson	Michigan	United States	49201
99	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan	United States	48144
100	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
101	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
102	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
103	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
104	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
105	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
106	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
107	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
108	St. John Macomb Hospital	Warren	Michigan	United States	48093
109	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
110	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
111	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
112	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
113	CCOP - Duluth	Duluth	Minnesota	United States	55805
114	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
115	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
116	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
117	Immanuel St. Joseph's	Mankato	Minnesota	United States	56002
118	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
119	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
120	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
121	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
122	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
123	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
124	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
125	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
126	United Hospital	Saint Paul	Minnesota	United States	55102
127	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
128	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
129	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
130	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
131	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
132	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
133	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
134	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
135	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
136	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
137	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
138	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
139	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
140		Great Falls	Montana	United States	59405
141	St. Peter's Hospital	Helena	Montana	United States	59601
142	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
143	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
144	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
145	Community Medical Center	Missoula	Montana	United States	59801
146	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
147	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
148	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
149	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
150	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
151	Immanuel Medical Center	Omaha	Nebraska	United States	68122
152	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
153	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
154	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
155	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
156	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
157	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
158	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
159	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
160	MeritCare Broadway	Fargo	North Dakota	United States	58122
161	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
162	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
163	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
164	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
165	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
166	CCOP - Columbus	Columbus	Ohio	United States	43215
167	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
168	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
169	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
170	Grandview Hospital	Dayton	Ohio	United States	45405
171	Good Samaritan Hospital	Dayton	Ohio	United States	45406
172	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
173	CCOP - Dayton	Dayton	Ohio	United States	45429
174	Grady Memorial Hospital	Delaware	Ohio	United States	43015
175	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
176	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
177	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
178	Fairfield Medical Center	Lancaster	Ohio	United States	43130
179	Lima Memorial Hospital	Lima	Ohio	United States	45804
180	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
181	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537
182	St. Luke's Hospital	Maumee	Ohio	United States	43537
183	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
184	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
185	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
186	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
187	Mercy Medical Center	Springfield	Ohio	United States	45504
188	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
189	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
190	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
191	Toledo Hospital	Toledo	Ohio	United States	43606
192	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
193	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
194	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
195	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
196	Fulton County Health Center	Wauseon	Ohio	United States	43567
197	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
198	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
199	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
200	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
201	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
202	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
203	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
204	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon	United States	97210
205	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
206	Adventist Medical Center	Portland	Oregon	United States	97216
207	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
208	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
209	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon	United States	97227
210	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
211	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
212	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania	United States	18201
213	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
214	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
215	Mercy Hospital at Wilkes-Barre	Wilkes-Barre	Pennsylvania	United States	18765
216	AnMed Cancer Center	Anderson	South Carolina	United States	29621
217	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
218	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
219	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
220	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
221	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
222	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
223	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
224	Cascade Cancer Center at Evergreen Hospital Medical Center	Kirkland	Washington	United States	98033
225	Olympic Medical Center	Port Angeles	Washington	United States	98362
226	Southlake Clinic	Renton	Washington	United States	98055
227	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
228	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
229	Central Wisconsin Cancer Program at Agnesian HealthCare	Fond du Lac	Wisconsin	United States	54935
230	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
231	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
232	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
233	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
234	Franciscan Skemp Healthcare - La Crosse Campus	La Crosse	Wisconsin	United States	54601
235	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
236	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
237	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
238	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)
• McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.

Investigators

• Study Chair: Amit Sood, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00376675
• Other Study ID Numbers: NCCTG-N05C7; NCI-2012-02701; CDR0000495148
• First Posted: Sep 15, 2006
• Last Update Posted: Aug 1, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Alliance for Clinical Trials in Oncology: fatigue; unspecified adult solid tumor, protocol specific
• Additional relevant MeSH terms: Fatigue; Methylphenidate

Study Results

Participant Flow

Recruitment Details	One-hundred and forty-eight (148) participants were recruited between February 2008 and August 2008 from 20 North Central Treatment Group (NCCTG) member sites.
Pre-assignment Detail	There were a total of 8 cancellations (5 Methylphenidate, 3 Placebo) and 1 ineligible participant on Placebo. These 9 participants were excluded from all analysis.

Arm/Group Title	Methylphenidate	Placebo
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.	Patients receive oral placebo daily on days 1-28.
Period Title: Overall Study
STARTED	69	70
COMPLETED	49	56
NOT COMPLETED	20	14

Baseline Characteristics

Arm/Group Title	Methylphenidate	Placebo	Total
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.	Patients receive oral placebo daily on days 1-28.	Total of all reporting groups
Overall Participants	69	70	139
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.2 (11.23)	60.6 (13.82)	59.9 (12.58)
Age, Customized (participants) [Number]
<50 years	14 20.3%	14 20%	28 20.1%
>=50 years	55 79.7%	56 80%	111 79.9%
Sex: Female, Male (Count of Participants)
Female	44 63.8%	40 57.1%	84 60.4%
Male	25 36.2%	30 42.9%	55 39.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 4.3%	5 7.1%	8 5.8%
White	66 95.7%	64 91.4%	130 93.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 1.4%	1 0.7%
Region of Enrollment (participants) [Number]
United States	69 100%	70 100%	139 100%
Current chemotherapy (participants) [Number]
Yes	44 63.8%	45 64.3%	89 64%
No	25 36.2%	25 35.7%	50 36%
Curative intent treatment (participants) [Number]
Missing	0 0%	2 2.9%	2 1.4%
Yes	34 49.3%	30 42.9%	64 46%
No	35 50.7%	38 54.3%	73 52.5%
Concurrent radiation (participants) [Number]
Yes	9 13%	7 10%	16 11.5%
No	60 87%	63 90%	123 88.5%
Concurrent biological therapy (participants) [Number]
Yes	17 24.6%	17 24.3%	34 24.5%
No	52 75.4%	53 75.7%	105 75.5%
Fatigue scale (participants) [Number]
4-7	47 68.1%	48 68.6%	95 68.3%
8-10	22 31.9%	22 31.4%	44 31.7%
Stage (participants) [Number]
0/I/II	22 31.9%	22 31.4%	44 31.7%
III/IV	47 68.1%	48 68.6%	95 68.3%
Type of cancer (participants) [Number]
Breast	26 37.7%	20 28.6%	46 33.1%
Colon	4 5.8%	4 5.7%	8 5.8%
Prostate	2 2.9%	6 8.6%	8 5.8%
Lung	10 14.5%	8 11.4%	18 12.9%
Combination/Unknown/Other	27 39.1%	32 45.7%	59 42.4%
Average fatigue over the last week (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	33.6 (15.43)	34.0 (17.23)	33.8 (16.30)
Average pain over the last 24 hours (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	87 (13.88)	86 (12.58)	86.3 (13.20)

Outcome Measures

1. Primary Outcome

Title	Prorated AUC of Total Fatigue as Measured by the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4
Description	The prorated area under the curve (AUC) for the usual fatigue question of the BFI at baseline and at weeks 1-4 after being translated onto a 0 (poor quality of life (QOL) or bad symptoms) to 100 (best QOL or no symptoms) point scale was calculated as the following: For those completed 4 weeks item: AUC/4; For those completed up to week 3 item: (AUC * 4) / 3; For those completed up to week 2 item: AUC * 2; For those completed up to week 1 item: AUC * 4; The prorated AUC scores were then transformed onto 0 to 100 point scale with 0 (poor QOL or bad symptoms) and 100 (best QOL or no symptoms) for analysis.
Time Frame	Baseline to week 4

Outcome Measure Data

Analysis Population Description

All participants meeting the eligibility criteria who have signed a consent form, started treatment, and provided a baseline and one post-baseline usual fatigue score were evaluable for this analysis.

Arm/Group Title	Methylphenidate	Placebo
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.	Patients receive oral placebo daily on days 1-28.
Measure Participants	62	63
Mean (Standard Deviation) [units on a scale]	50.33 (20.32)	47.15 (17.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methylphenidate, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.317
	Comments
	Method	Wilcoxon rank sum test
	Comments

2. Secondary Outcome

Title	Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4
Description	The Symptom Experience Diary (SED) consists of 12 items. All scores were translated onto a 0-100 point scale, with 0 represent poor quality of life (QOL) or bad symptom and 100 is best QOL or no symptoms.The change in severity of adverse events was calculated as subtracting the item scores at baseline from the scores at week 4.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

All participants who have provided a baseline and week 4 SED scores were evaluable for this analysis.

Arm/Group Title	Methylphenidate	Placebo
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.	Patients receive oral placebo daily on days 1-28.
Measure Participants	49	56
Nervousness	-2.7 (20.08)	9.5 (17.15)
Appetite decrease	-5.2 (21.04)	6.6 (28.87)
Sex drive	-0.9 (22.63)	9.8 (37.17)
Abdominal pain	-3.5 (21.85)	3.6 (19.49)
Dizziness	-2.2 (15.58)	2.1 (17.76)
Shakiness	-0.6 (11.97)	1.4 (18.82)
Heartbeat	-2.0 (10.60)	-1.6 (16.60)
Vomiting	-0.8 (9.19)	0.4 (18.29)
Headaches	-0.8 (18.80)	3.9 (17.34)
Trouble sleeping	10.6 (29.99)	11.1 (28.58)
Fatigue distress	22.9 (32.94)	15.8 (33.25)
Fatigue control satisfaction	28.0 (32.77)	23.2 (34.57)

3. Secondary Outcome

Title	AUC of Sleep Quality as Measured by the Pittsburgh Sleep Quality Index at Baseline and at Weeks 1-4
Description	Pittsburgh Sleep Quality Index (PSQI) consists of 19 items and 7 scales. The AUC for the overall PSQI at baseline and at weeks 1-4 after being translated onto a 0 to 100 point scale was calculated. Higher scores are better.
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

All participants who have provided a baseline and one post-baseline PSQI score were evaluable for this analysis.

Arm/Group Title	Methylphenidate	Placebo
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.	Patients receive oral placebo daily on days 1-28.
Measure Participants	63	65
Mean (Standard Deviation) [units on a scale * weeks]	144.37 (110.32)	145.93 (108.21)

4. Secondary Outcome

Title	AUC of Vitality as Measured by the Short Form-36 Vitality Subscale at Baseline and at Weeks 1-4
Description	The SF-36 is a 36-item short form to measure health status in various populations. The vitality subscale is comprised of 4 items and is a measure of energy level as well as fatigue. The AUC for the vitality subscale at baseline and at weeks 1-4 after being translated onto a 0 to 100 point scale was calculated. Higher scores are better.
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

All participants who have provided a baseline and one post-baseline Vitality subscale score were evaluable for this analysis.

Arm/Group Title	Methylphenidate	Placebo
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.	Patients receive oral placebo daily on days 1-28.
Measure Participants	69	68
Mean (Standard Deviation) [units on a scale * weeks]	134.74 (88.77)	121.59 (76.31)

5. Secondary Outcome

Title	AUC of Overall Quality of Life (QOL) and QOL Domains as Measured by the Linear Analogue Self Assessment at Baseline and at Weeks 1-4
Description	Linear Analogue Self Assessment (LASA) consists of 6 single-item numeric analogue scales. The AUC for the six-items at baseline and at weeks 1-4 after being translated onto a 0 to 100 point scale was calculated. Higher scores are better.
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

All participants who have provided a baseline and one post-baseline LASA score were evaluable for this analysis.

Arm/Group Title	Methylphenidate	Placebo
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.	Patients receive oral placebo daily on days 1-28.
Measure Participants	68	68
Overall QOL	204.21 (103.16)	201.34 (94.65)
Mental well-being	227.04 (109.61)	226.40 (100.62)
Physical well-being	188.13 (98.12)	191.07 (87.23)
Emotional well-being	203.65 (105.32)	215.65 (96.90)
Social activity	189.68 (112.89)	177.34 (95.99)
Spiritual well-being	231.24 (122.30)	255.88 (113.74)

6. Secondary Outcome

Title	AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4
Description	Area under the curve (AUC) for the other fatigue items of the BFI at baseline and at weeks 1-4 after being translated onto a 0 to 100 point scale was calculated. Higher scores are better.
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

All participants who have provided a baseline and one post-baseline BFI score were evaluable for this analysis.

Arm/Group Title	Methylphenidate	Placebo
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.	Patients receive oral placebo daily on days 1-28.
Measure Participants	68	69
Fatigue right now	179.96 (100.06)	174.94 (92.95)
Worst fatigue last 24 hours	144.59 (92.95)	126.36 (82.13)
Fatigue interference with general activity	187.60 (106.88)	171.06 (98.11)
Fatigue interference with mood	205.31 (106.89)	220.29 (114.85)
Fatigue interference with walking ability	210.09 (125.36)	206.46 (120.76)
Fatigue interference with normal work	179.94 (106.40)	168.84 (104.20)
Fatigue interference with relations with others	224.72 (114.46)	243.87 (115.95)
Fatigue interference with enjoyment of life	194.15 (115.11)	184.12 (111.10)

7. Secondary Outcome

Title	Anchor-based Minimally Important Difference in SGIC Overall Quality of Life Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue
Description	Perceived treatment efficacy was measured by the Subject Global Impression of Change (SGIC). The SGIC is a 3-point item in which the patient rates the change in the overall status since beginning the study drug (ranging from very much better, moderately better, a little better, about the same, a little worse, moderately worse, to very much worse). The average change in patient fatigue scores for those participants who express a perceived change of "a little better" via the SGIC scores were calculated. BFI usual fatigue item score was translated into 0 to 100 point scale for the analysis, with 0 (poor QOL or bad symptoms) and 100 (best QOL or no symptoms).
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

All participants who have provided a baseline and week 4 BFI usual fatigue scores and a perceived change of "a little better" via SGIC scores.

Arm/Group Title	Methylphenidate	Placebo
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.	Patients receive oral placebo daily on days 1-28.
Measure Participants	11	10
Mean (Standard Deviation) [units on a scale]	20.9 (18.1)	15 (22.2)

8. Secondary Outcome

Title	Anchor-based Minimally Important Difference in SGIC Physical Condition Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue
Description	Perceived treatment efficacy was measured by the Subject Global Impression of Change (SGIC). The SGIC is a 3-point item in which the patient rates the change in the overall status since beginning the study drug (ranging from very much better, moderately better, a little better, about the same, a little worse, moderately worse, to very much worse). The average change in patient fatigue scores for those participants who express a perceived change of "a little better" via the SGIC scores were calculated. BFI usual fatigue item score was translated into 0 to 100 point scale for the analysis, with 0 (poor QOL or bad symptoms) and 100 (best QOL or no symptoms).
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

All participants who have provided a baseline and week 4 BFI usual fatigue scores and a perceived change of "a little better" via SGIC scores.

Arm/Group Title	Methylphenidate	Placebo
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.	Patients receive oral placebo daily on days 1-28.
Measure Participants	13	7
Mean (Standard Deviation) [Units on scale]	20.0 (14.7)	11.4 (27.3)

9. Secondary Outcome

Title	Anchor-based Minimally Important Difference in SGIC Emotional State Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue
Description	Perceived treatment efficacy was measured by the Subject Global Impression of Change (SGIC). The SGIC is a 3-point item in which the patient rates the change in the overall status since beginning the study drug (ranging from very much better, moderately better, a little better, about the same, a little worse, moderately worse, to very much worse). The average change in patient fatigue scores for those participants who express a perceived change of "a little better" via the SGIC scores were calculated. BFI usual fatigue item score was translated into 0 to 100 point scale for the analysis, with 0 (poor QOL or bad symptoms) and 100 (best QOL or no symptoms).
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

All participants who have provided a baseline and week 4 BFI usual fatigue scores and a perceived change of "a little better" via SGIC scores.

Arm/Group Title	Methylphenidate	Placebo
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.	Patients receive oral placebo daily on days 1-28.
Measure Participants	10	13
Mean (Standard Deviation) [Units on scale]	31.0 (24.7)	23.8 (29.3)

Adverse Events

Time Frame	4 weeks
Adverse Event Reporting Description	One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Arm/Group Title	Methylphenidate		Placebo
Arm/Group Description	Patients receive oral methylphenidate daily on days 1-28.		Patients receive oral placebo daily on days 1-28.
All Cause Mortality
	Methylphenidate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Methylphenidate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/69 (0%)
Other (Not Including Serious) Adverse Events
	Methylphenidate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/68 (82.4%)		54/69 (78.3%)
Blood and lymphatic system disorders
Hemoglobin decreased	0/68 (0%)	0	1/69 (1.4%)	1
Cardiac disorders
Palpitations	1/68 (1.5%)	1	0/69 (0%)	0
Gastrointestinal disorders
Abdominal pain	16/68 (23.5%)	33	21/69 (30.4%)	53
Constipation	0/68 (0%)	0	1/69 (1.4%)	2
Diarrhea	1/68 (1.5%)	1	0/69 (0%)	0
Flatulence	1/68 (1.5%)	2	0/69 (0%)	0
Nausea	1/68 (1.5%)	1	0/69 (0%)	0
Vomiting	0/68 (0%)	0	1/69 (1.4%)	2
General disorders
Disease progression	0/68 (0%)	0	1/69 (1.4%)	1
Fatigue	2/68 (2.9%)	5	4/69 (5.8%)	9
Fever	0/68 (0%)	0	1/69 (1.4%)	1
Infections and infestations
Infection	0/68 (0%)	0	1/69 (1.4%)	3
Injury, poisoning and procedural complications
Bruising	1/68 (1.5%)	1	0/69 (0%)	0
Fracture	1/68 (1.5%)	1	0/69 (0%)	0
Investigations
Leukocyte count decreased	2/68 (2.9%)	2	0/69 (0%)	0
Lymphocyte count decreased	0/68 (0%)	0	1/69 (1.4%)	1
Neutrophil count decreased	1/68 (1.5%)	1	0/69 (0%)	0
Platelet count decreased	0/68 (0%)	0	1/69 (1.4%)	1
Metabolism and nutrition disorders
Anorexia	2/68 (2.9%)	2	1/69 (1.4%)	1
Blood glucose increased	0/68 (0%)	0	1/69 (1.4%)	1
Serum albumin decreased	0/68 (0%)	0	1/69 (1.4%)	1
Serum potassium decreased	0/68 (0%)	0	1/69 (1.4%)	1
Serum sodium decreased	0/68 (0%)	0	2/69 (2.9%)	2
Musculoskeletal and connective tissue disorders
Back pain	0/68 (0%)	0	2/69 (2.9%)	4
Nervous system disorders
Dizziness	18/68 (26.5%)	40	25/69 (36.2%)	58
Headache	28/68 (41.2%)	55	21/69 (30.4%)	39
Intracranial hemorrhage	1/68 (1.5%)	1	0/69 (0%)	0
Peripheral sensory neuropathy	0/68 (0%)	0	1/69 (1.4%)	1
Syncope	1/68 (1.5%)	1	1/69 (1.4%)	1
Tremor	1/68 (1.5%)	1	1/69 (1.4%)	1
Psychiatric disorders
Anxiety	24/68 (35.3%)	44	24/69 (34.8%)	66
Confusion	0/68 (0%)	0	1/69 (1.4%)	1
Depression	1/68 (1.5%)	1	1/69 (1.4%)	1
Insomnia	37/68 (54.4%)	80	32/69 (46.4%)	80
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/68 (0%)	0	1/69 (1.4%)	1
Skin and subcutaneous tissue disorders
Alopecia	0/68 (0%)	0	1/69 (1.4%)	4
Rash desquamating	1/68 (1.5%)	1	0/69 (0%)	0
Sweating	0/68 (0%)	0	1/69 (1.4%)	1
Vascular disorders
Hypotension	0/68 (0%)	0	1/69 (1.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.