Trial Outcomes & Findings for Methylphenidate in Treating Patients With Fatigue Caused by Cancer (NCT NCT00376675)

Last Updated: 2016-08-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

148 participants

Primary outcome timeframe

Baseline to week 4

Results posted on

2016-08-01

Participant Flow

One-hundred and forty-eight (148) participants were recruited between February 2008 and August 2008 from 20 North Central Treatment Group (NCCTG) member sites.

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.

Participant milestones

Participant milestones
Measure	Methylphenidate Patients receive oral methylphenidate daily on days 1-28.	Placebo Patients receive oral placebo daily on days 1-28.
Overall Study STARTED	69	70
Overall Study COMPLETED	49	56
Overall Study NOT COMPLETED	20	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Methylphenidate Patients receive oral methylphenidate daily on days 1-28.	Placebo Patients receive oral placebo daily on days 1-28.
Overall Study Withdrawal by Subject	9	2
Overall Study Adverse Event	10	5
Overall Study Other Reason	1	7

Baseline Characteristics

Methylphenidate in Treating Patients With Fatigue Caused by Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methylphenidate n=69 Participants Patients receive oral methylphenidate daily on days 1-28.	Placebo n=70 Participants Patients receive oral placebo daily on days 1-28.	Total n=139 Participants Total of all reporting groups
Age, Continuous	59.2 years STANDARD_DEVIATION 11.23 • n=5 Participants	60.6 years STANDARD_DEVIATION 13.82 • n=7 Participants	59.9 years STANDARD_DEVIATION 12.58 • n=5 Participants
Age, Customized <50 years	14 participants n=5 Participants	14 participants n=7 Participants	28 participants n=5 Participants
Age, Customized >=50 years	55 participants n=5 Participants	56 participants n=7 Participants	111 participants n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	40 Participants n=7 Participants	84 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	30 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	66 Participants n=5 Participants	64 Participants n=7 Participants	130 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	69 participants n=5 Participants	70 participants n=7 Participants	139 participants n=5 Participants
Current chemotherapy Yes	44 participants n=5 Participants	45 participants n=7 Participants	89 participants n=5 Participants
Current chemotherapy No	25 participants n=5 Participants	25 participants n=7 Participants	50 participants n=5 Participants
Curative intent treatment Missing	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Curative intent treatment Yes	34 participants n=5 Participants	30 participants n=7 Participants	64 participants n=5 Participants
Curative intent treatment No	35 participants n=5 Participants	38 participants n=7 Participants	73 participants n=5 Participants
Concurrent radiation Yes	9 participants n=5 Participants	7 participants n=7 Participants	16 participants n=5 Participants
Concurrent radiation No	60 participants n=5 Participants	63 participants n=7 Participants	123 participants n=5 Participants
Concurrent biological therapy Yes	17 participants n=5 Participants	17 participants n=7 Participants	34 participants n=5 Participants
Concurrent biological therapy No	52 participants n=5 Participants	53 participants n=7 Participants	105 participants n=5 Participants
Fatigue scale 4-7	47 participants n=5 Participants	48 participants n=7 Participants	95 participants n=5 Participants
Fatigue scale 8-10	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants
Stage 0/I/II	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants
Stage III/IV	47 participants n=5 Participants	48 participants n=7 Participants	95 participants n=5 Participants
Type of cancer Breast	26 participants n=5 Participants	20 participants n=7 Participants	46 participants n=5 Participants
Type of cancer Colon	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Type of cancer Prostate	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants
Type of cancer Lung	10 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants
Type of cancer Combination/Unknown/Other	27 participants n=5 Participants	32 participants n=7 Participants	59 participants n=5 Participants
Average fatigue over the last week	33.6 units on a scale STANDARD_DEVIATION 15.43 • n=5 Participants	34.0 units on a scale STANDARD_DEVIATION 17.23 • n=7 Participants	33.8 units on a scale STANDARD_DEVIATION 16.30 • n=5 Participants
Average pain over the last 24 hours	87 units on a scale STANDARD_DEVIATION 13.88 • n=5 Participants	86 units on a scale STANDARD_DEVIATION 12.58 • n=7 Participants	86.3 units on a scale STANDARD_DEVIATION 13.20 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Methylphenidate n=62 Participants Patients receive oral methylphenidate daily on days 1-28.	Placebo n=63 Participants Patients receive oral placebo daily on days 1-28.
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	47.15 units on a scale Standard Deviation 17.00

SECONDARY outcome

Timeframe: Baseline and Week 4

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

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.

Outcome measures

Outcome measures
Measure	Methylphenidate n=49 Participants Patients receive oral methylphenidate daily on days 1-28.	Placebo n=56 Participants Patients receive oral placebo daily on days 1-28.
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	9.8 units on a scale Standard Deviation 37.17
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	11.1 units on a scale Standard Deviation 28.58
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	9.5 units on a scale Standard Deviation 17.15
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	6.6 units on a scale Standard Deviation 28.87
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	3.6 units on a scale Standard Deviation 19.49
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	2.1 units on a scale Standard Deviation 17.76
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	1.4 units on a scale Standard Deviation 18.82
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 10.60	-1.6 units on a scale Standard Deviation 16.60
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	0.4 units on a scale Standard Deviation 18.29
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 18.80	3.9 units on a scale Standard Deviation 17.34
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	15.8 units on a scale Standard Deviation 33.25
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	23.2 units on a scale Standard Deviation 34.57

SECONDARY outcome

Timeframe: Baseline to Week 4

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

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.

Outcome measures

Outcome measures
Measure	Methylphenidate n=63 Participants Patients receive oral methylphenidate daily on days 1-28.	Placebo n=65 Participants Patients receive oral placebo daily on days 1-28.
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	145.93 units on a scale * weeks Standard Deviation 108.21

SECONDARY outcome

Timeframe: Baseline to Week 4

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

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.

Outcome measures

Outcome measures
Measure	Methylphenidate n=69 Participants Patients receive oral methylphenidate daily on days 1-28.	Placebo n=68 Participants Patients receive oral placebo daily on days 1-28.
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	121.59 units on a scale * weeks Standard Deviation 76.31

SECONDARY outcome

Timeframe: Baseline to Week 4

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

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.

Outcome measures

Outcome measures
Measure	Methylphenidate n=68 Participants Patients receive oral methylphenidate daily on days 1-28.	Placebo n=68 Participants Patients receive oral placebo daily on days 1-28.
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	201.34 units on a scale * weeks Standard Deviation 94.65
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	226.40 units on a scale * weeks Standard Deviation 100.62
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	191.07 units on a scale * weeks Standard Deviation 87.23
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	215.65 units on a scale * weeks Standard Deviation 96.90
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	177.34 units on a scale * weeks Standard Deviation 95.99
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 122.30	255.88 units on a scale * weeks Standard Deviation 113.74

SECONDARY outcome

Timeframe: Baseline to Week 4

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

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.

Outcome measures

Outcome measures
Measure	Methylphenidate n=68 Participants Patients receive oral methylphenidate daily on days 1-28.	Placebo n=69 Participants Patients receive oral placebo daily on days 1-28.
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	174.94 units on a scale * weeks Standard Deviation 92.95
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	126.36 units on a scale * weeks Standard Deviation 82.13
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	171.06 units on a scale * weeks Standard Deviation 98.11
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	220.29 units on a scale * weeks Standard Deviation 114.85
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	206.46 units on a scale * weeks Standard Deviation 120.76
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 106.40	168.84 units on a scale * weeks Standard Deviation 104.20
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	243.87 units on a scale * weeks Standard Deviation 115.95
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	184.12 units on a scale * weeks Standard Deviation 111.10

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Methylphenidate n=11 Participants Patients receive oral methylphenidate daily on days 1-28.	Placebo n=10 Participants Patients receive oral placebo daily on days 1-28.
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	15 units on a scale Standard Deviation 22.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Methylphenidate n=13 Participants Patients receive oral methylphenidate daily on days 1-28.	Placebo n=7 Participants Patients receive oral placebo daily on days 1-28.
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	11.4 Units on scale Standard Deviation 27.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Methylphenidate n=10 Participants Patients receive oral methylphenidate daily on days 1-28.	Placebo n=13 Participants Patients receive oral placebo daily on days 1-28.
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	23.8 Units on scale Standard Deviation 29.3

Adverse Events

Methylphenidate

Serious events: 0 serious events

Other events: 56 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Amit Sood

Mayo Clinic

Phone: 507-284-1623

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Methylphenidate n=68 participants at risk Patients receive oral methylphenidate daily on days 1-28.	Placebo n=69 participants at risk Patients receive oral placebo daily on days 1-28.
Blood and lymphatic system disorders Hemoglobin decreased	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Cardiac disorders Palpitations	1.5% 1/68 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	0.00% 0/69 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Gastrointestinal disorders Abdominal pain	23.5% 16/68 • Number of events 33 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	30.4% 21/69 • Number of events 53 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Gastrointestinal disorders Constipation	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 2 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Gastrointestinal disorders Diarrhea	1.5% 1/68 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	0.00% 0/69 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Gastrointestinal disorders Flatulence	1.5% 1/68 • Number of events 2 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	0.00% 0/69 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Gastrointestinal disorders Nausea	1.5% 1/68 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	0.00% 0/69 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Gastrointestinal disorders Vomiting	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 2 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
General disorders Disease progression	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
General disorders Fatigue	2.9% 2/68 • Number of events 5 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	5.8% 4/69 • Number of events 9 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
General disorders Fever	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Infections and infestations Infection	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 3 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Injury, poisoning and procedural complications Bruising	1.5% 1/68 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	0.00% 0/69 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Injury, poisoning and procedural complications Fracture	1.5% 1/68 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	0.00% 0/69 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Investigations Leukocyte count decreased	2.9% 2/68 • Number of events 2 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	0.00% 0/69 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Investigations Lymphocyte count decreased	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Investigations Neutrophil count decreased	1.5% 1/68 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	0.00% 0/69 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Investigations Platelet count decreased	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Metabolism and nutrition disorders Anorexia	2.9% 2/68 • Number of events 2 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Metabolism and nutrition disorders Blood glucose increased	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Metabolism and nutrition disorders Serum albumin decreased	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Metabolism and nutrition disorders Serum potassium decreased	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Metabolism and nutrition disorders Serum sodium decreased	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	2.9% 2/69 • Number of events 2 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	2.9% 2/69 • Number of events 4 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Nervous system disorders Dizziness	26.5% 18/68 • Number of events 40 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	36.2% 25/69 • Number of events 58 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Nervous system disorders Headache	41.2% 28/68 • Number of events 55 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	30.4% 21/69 • Number of events 39 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Nervous system disorders Intracranial hemorrhage	1.5% 1/68 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	0.00% 0/69 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Nervous system disorders Syncope	1.5% 1/68 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Nervous system disorders Tremor	1.5% 1/68 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Psychiatric disorders Anxiety	35.3% 24/68 • Number of events 44 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	34.8% 24/69 • Number of events 66 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Psychiatric disorders Confusion	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Psychiatric disorders Depression	1.5% 1/68 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Psychiatric disorders Insomnia	54.4% 37/68 • Number of events 80 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	46.4% 32/69 • Number of events 80 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 4 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Skin and subcutaneous tissue disorders Rash desquamating	1.5% 1/68 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	0.00% 0/69 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Skin and subcutaneous tissue disorders Sweating	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.
Vascular disorders Hypotension	0.00% 0/68 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.	1.4% 1/69 • Number of events 1 • 4 weeks One participant on Methylphenidate and one participant on placebo did not have adverse event data provided post baseline.