Fatigue, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
fatigue, unspecified adult solid tumor, protocol specific
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.
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.
Interventions
DRUGmethylphenidate hydrochloride
Given orally
OTHERplacebo
Given orally
Sponsors
National Cancer Institute (NCI)
McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 8. Willing and able to provide informed consent 9. Negative pregnancy test (urine or serum) done ≤ 7 days prior to registration, for women of childbearing potential only 10. Ability to complete questionnaire(s) by themselves or with assistance 11. Biological therapy (i.e. immunotherapy, biotherapy), chemotherapy or radiation therapy will be allowed 12. Use of a stable dose of anti-depressants (except tricyclic anti-depressants) will be allowed 13. 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. 11. 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. 12. 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. 13. Untreated hypothyroidism (TSH ≥ 5)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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: 1. For those completed 4 weeks item: AUC/4; 2. For those completed up to week 3 item: (AUC \* 4) / 3; 3. For those completed up to week 2 item: AUC \* 2; 4. 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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). |
| 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). |
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Methylphenidate Patients receive oral methylphenidate daily on days 1-28. | 69 |
| Placebo Patients receive oral placebo daily on days 1-28. | 70 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 |
| Overall Study | Other Reason | 1 | 7 |
| Overall Study | Withdrawal by Subject | 9 | 2 |
Baseline characteristics
| Characteristic | Total | Methylphenidate | Placebo |
|---|---|---|---|
| Age, Continuous | 59.9 years STANDARD_DEVIATION 12.58 | 59.2 years STANDARD_DEVIATION 11.23 | 60.6 years STANDARD_DEVIATION 13.82 |
| Age, Customized <50 years | 28 participants | 14 participants | 14 participants |
| Age, Customized >=50 years | 111 participants | 55 participants | 56 participants |
| Average fatigue over the last week | 33.8 units on a scale STANDARD_DEVIATION 16.3 | 33.6 units on a scale STANDARD_DEVIATION 15.43 | 34.0 units on a scale STANDARD_DEVIATION 17.23 |
| Average pain over the last 24 hours | 86.3 units on a scale STANDARD_DEVIATION 13.2 | 87 units on a scale STANDARD_DEVIATION 13.88 | 86 units on a scale STANDARD_DEVIATION 12.58 |
| Concurrent biological therapy No | 105 participants | 52 participants | 53 participants |
| Concurrent biological therapy Yes | 34 participants | 17 participants | 17 participants |
| Concurrent radiation No | 123 participants | 60 participants | 63 participants |
| Concurrent radiation Yes | 16 participants | 9 participants | 7 participants |
| Curative intent treatment Missing | 2 participants | 0 participants | 2 participants |
| Curative intent treatment No | 73 participants | 35 participants | 38 participants |
| Curative intent treatment Yes | 64 participants | 34 participants | 30 participants |
| Current chemotherapy No | 50 participants | 25 participants | 25 participants |
| Current chemotherapy Yes | 89 participants | 44 participants | 45 participants |
| Fatigue scale 4-7 | 95 participants | 47 participants | 48 participants |
| Fatigue scale 8-10 | 44 participants | 22 participants | 22 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 130 Participants | 66 Participants | 64 Participants |
| Region of Enrollment United States | 139 participants | 69 participants | 70 participants |
| Sex: Female, Male Female | 84 Participants | 44 Participants | 40 Participants |
| Sex: Female, Male Male | 55 Participants | 25 Participants | 30 Participants |
| Stage 0/I/II | 44 participants | 22 participants | 22 participants |
| Stage III/IV | 95 participants | 47 participants | 48 participants |
| Type of cancer Breast | 46 participants | 26 participants | 20 participants |
| Type of cancer Colon | 8 participants | 4 participants | 4 participants |
| Type of cancer Combination/Unknown/Other | 59 participants | 27 participants | 32 participants |
| Type of cancer Lung | 18 participants | 10 participants | 8 participants |
| Type of cancer Prostate | 8 participants | 2 participants | 6 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 56 / 68 | 54 / 69 |
| serious Total, serious adverse events | 0 / 68 | 0 / 69 |
Outcome results
Primary
Prorated AUC of Total Fatigue as Measured by the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4
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: 1. For those completed 4 weeks item: AUC/4; 2. For those completed up to week 3 item: (AUC \* 4) / 3; 3. For those completed up to week 2 item: AUC \* 2; 4. 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | Prorated AUC of Total Fatigue as Measured by the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | 50.33 units on a scale | Standard Deviation 20.32 |
| Placebo | Prorated AUC of Total Fatigue as Measured by the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | 47.15 units on a scale | Standard Deviation 17 |
p-value: 0.317Wilcoxon rank sum test
Secondary
Anchor-based Minimally Important Difference in SGIC Emotional State Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | Anchor-based Minimally Important Difference in SGIC Emotional State Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue | 31.0 Units on scale | Standard Deviation 24.7 |
| Placebo | Anchor-based Minimally Important Difference in SGIC Emotional State Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue | 23.8 Units on scale | Standard Deviation 29.3 |
Secondary
Anchor-based Minimally Important Difference in SGIC Overall Quality of Life Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | Anchor-based Minimally Important Difference in SGIC Overall Quality of Life Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue | 20.9 units on a scale | Standard Deviation 18.1 |
| Placebo | Anchor-based Minimally Important Difference in SGIC Overall Quality of Life Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue | 15 units on a scale | Standard Deviation 22.2 |
Secondary
Anchor-based Minimally Important Difference in SGIC Physical Condition Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | Anchor-based Minimally Important Difference in SGIC Physical Condition Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue | 20.0 Units on scale | Standard Deviation 14.7 |
| Placebo | Anchor-based Minimally Important Difference in SGIC Physical Condition Based on Mean Changes From Baseline to Week 4 on BFI Usual Fatigue | 11.4 Units on scale | Standard Deviation 27.3 |
Secondary
AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4
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.
Time frame: Baseline to Week 4
Population: All participants who have provided a baseline and one post-baseline BFI score were evaluable for this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue right now | 179.96 units on a scale * weeks | Standard Deviation 100.06 |
| Methylphenidate | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Worst fatigue last 24 hours | 144.59 units on a scale * weeks | Standard Deviation 92.95 |
| Methylphenidate | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with general activity | 187.60 units on a scale * weeks | Standard Deviation 106.88 |
| Methylphenidate | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with mood | 205.31 units on a scale * weeks | Standard Deviation 106.89 |
| Methylphenidate | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with walking ability | 210.09 units on a scale * weeks | Standard Deviation 125.36 |
| Methylphenidate | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with normal work | 179.94 units on a scale * weeks | Standard Deviation 106.4 |
| Methylphenidate | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with relations with others | 224.72 units on a scale * weeks | Standard Deviation 114.46 |
| Methylphenidate | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with enjoyment of life | 194.15 units on a scale * weeks | Standard Deviation 115.11 |
| Placebo | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with enjoyment of life | 184.12 units on a scale * weeks | Standard Deviation 111.1 |
| Placebo | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue right now | 174.94 units on a scale * weeks | Standard Deviation 92.95 |
| Placebo | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with walking ability | 206.46 units on a scale * weeks | Standard Deviation 120.76 |
| Placebo | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Worst fatigue last 24 hours | 126.36 units on a scale * weeks | Standard Deviation 82.13 |
| Placebo | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with relations with others | 243.87 units on a scale * weeks | Standard Deviation 115.95 |
| Placebo | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with general activity | 171.06 units on a scale * weeks | Standard Deviation 98.11 |
| Placebo | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with normal work | 168.84 units on a scale * weeks | Standard Deviation 104.2 |
| Placebo | AUC of Other Fatigue Scores as Measured by Items of the Brief Fatigue Inventory (BFI) at Baseline and at Weeks 1-4 | Fatigue interference with mood | 220.29 units on a scale * weeks | Standard Deviation 114.85 |
Secondary
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
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
Population: All participants who have provided a baseline and one post-baseline LASA score were evaluable for this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate | 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 | Overall QOL | 204.21 units on a scale * weeks | Standard Deviation 103.16 |
| Methylphenidate | 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 | Mental well-being | 227.04 units on a scale * weeks | Standard Deviation 109.61 |
| Methylphenidate | 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 | Physical well-being | 188.13 units on a scale * weeks | Standard Deviation 98.12 |
| Methylphenidate | 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 | Emotional well-being | 203.65 units on a scale * weeks | Standard Deviation 105.32 |
| Methylphenidate | 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 | Social activity | 189.68 units on a scale * weeks | Standard Deviation 112.89 |
| Methylphenidate | 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 | Spiritual well-being | 231.24 units on a scale * weeks | Standard Deviation 122.3 |
| Placebo | 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 | Social activity | 177.34 units on a scale * weeks | Standard Deviation 95.99 |
| Placebo | 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 | Overall QOL | 201.34 units on a scale * weeks | Standard Deviation 94.65 |
| Placebo | 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 | Emotional well-being | 215.65 units on a scale * weeks | Standard Deviation 96.9 |
| Placebo | 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 | Mental well-being | 226.40 units on a scale * weeks | Standard Deviation 100.62 |
| Placebo | 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 | Spiritual well-being | 255.88 units on a scale * weeks | Standard Deviation 113.74 |
| Placebo | 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 | Physical well-being | 191.07 units on a scale * weeks | Standard Deviation 87.23 |
Secondary
AUC of Sleep Quality as Measured by the Pittsburgh Sleep Quality Index at Baseline and at Weeks 1-4
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.
Time frame: Baseline to Week 4
Population: All participants who have provided a baseline and one post-baseline PSQI score were evaluable for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | AUC of Sleep Quality as Measured by the Pittsburgh Sleep Quality Index at Baseline and at Weeks 1-4 | 144.37 units on a scale * weeks | Standard Deviation 110.32 |
| Placebo | AUC of Sleep Quality as Measured by the Pittsburgh Sleep Quality Index at Baseline and at Weeks 1-4 | 145.93 units on a scale * weeks | Standard Deviation 108.21 |
Secondary
AUC of Vitality as Measured by the Short Form-36 Vitality Subscale at Baseline and at Weeks 1-4
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.
Time frame: Baseline to Week 4
Population: All participants who have provided a baseline and one post-baseline Vitality subscale score were evaluable for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | AUC of Vitality as Measured by the Short Form-36 Vitality Subscale at Baseline and at Weeks 1-4 | 134.74 units on a scale * weeks | Standard Deviation 88.77 |
| Placebo | AUC of Vitality as Measured by the Short Form-36 Vitality Subscale at Baseline and at Weeks 1-4 | 121.59 units on a scale * weeks | Standard Deviation 76.31 |
Secondary
Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to 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.
Time frame: Baseline and Week 4
Population: All participants who have provided a baseline and week 4 SED scores were evaluable for this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Nervousness | -2.7 units on a scale | Standard Deviation 20.08 |
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Appetite decrease | -5.2 units on a scale | Standard Deviation 21.04 |
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Sex drive | -0.9 units on a scale | Standard Deviation 22.63 |
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Abdominal pain | -3.5 units on a scale | Standard Deviation 21.85 |
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Dizziness | -2.2 units on a scale | Standard Deviation 15.58 |
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Shakiness | -0.6 units on a scale | Standard Deviation 11.97 |
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Heartbeat | -2.0 units on a scale | Standard Deviation 10.6 |
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Vomiting | -0.8 units on a scale | Standard Deviation 9.19 |
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Headaches | -0.8 units on a scale | Standard Deviation 18.8 |
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Trouble sleeping | 10.6 units on a scale | Standard Deviation 29.99 |
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Fatigue distress | 22.9 units on a scale | Standard Deviation 32.94 |
| Methylphenidate | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Fatigue control satisfaction | 28.0 units on a scale | Standard Deviation 32.77 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Fatigue distress | 15.8 units on a scale | Standard Deviation 33.25 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Nervousness | 9.5 units on a scale | Standard Deviation 17.15 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Heartbeat | -1.6 units on a scale | Standard Deviation 16.6 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Appetite decrease | 6.6 units on a scale | Standard Deviation 28.87 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Trouble sleeping | 11.1 units on a scale | Standard Deviation 28.58 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Sex drive | 9.8 units on a scale | Standard Deviation 37.17 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Vomiting | 0.4 units on a scale | Standard Deviation 18.29 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Abdominal pain | 3.6 units on a scale | Standard Deviation 19.49 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Fatigue control satisfaction | 23.2 units on a scale | Standard Deviation 34.57 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Dizziness | 2.1 units on a scale | Standard Deviation 17.76 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Headaches | 3.9 units on a scale | Standard Deviation 17.34 |
| Placebo | Severity of Adverse Events as Measured by the Symptom Experience Diary Based on Mean Changes From Baseline to Week 4 | Shakiness | 1.4 units on a scale | Standard Deviation 18.82 |