Levocarnitine in Treating Fatigue in Cancer Patients

• Sponsor: ECOG-ACRIN Cancer Research Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00091169
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 376
• Locations: 116
• Arms: 2
• Duration (Months): 65.9
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Levocarnitine may help improve energy levels in cancer patients.

PURPOSE: This randomized phase III trial is studying how well levocarnitine works compared to a placebo in treating fatigue in cancer patients.

Condition or Disease	Intervention/Treatment	Phase
Fatigue; Unspecified Adult Solid Tumor, Protocol Specific	Dietary Supplement: levocarnitine; Other: placebo	Phase 3

Detailed Description

OBJECTIVES:

Primary Objective:

• Compare the efficacy of levocarnitine (L-carnitine) supplementation vs placebo for the management of fatigue in patients with cancer.

Secondary Objectives:

• Assess the effect of levocarnitine on pain, depression and performance status at 4 and 8 weeks of follow-up.

• Determine the prevalence of serum carnitine deficiency in patients treated with these regimens.

• Explore the association between carnitine deficiency and fatigue.

• Present the toxicity profiles of all patients.

Correlative Objective:

• Measure serum levels of the pro-inflammatory cytokines and growth factors and correlate with fatigue and other onco-behavioral symptoms.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to gender, ECOG performance status (0-1 vs 2-3), and concurrent chemotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms in a 1:1 ratio.

• Arm I (levocarnitine): Patients receive oral levocarnitine (L-carnitine) twice daily (2000 mg/day) on weeks 1-4.

• Arm II (placebo): Patients receive oral placebo twice daily (2000 mg/day) on weeks 1-4.

The dose was titrated over a 2-day period (i.e. two 500 mg doses the first day and two 1000 mg doses the second day) to avoid gastrointestinal side effects. Patients then continued to receive two daily doses of 1000 mg on days 3 to 28.

After week 4, all patients (on both arms) receive open-label oral L-carnitine twice daily on weeks 5-8 (extension phase) administered in the same fashion as during the first 4 weeks. For patients who had received a dose modification during weeks 1 to 4, they received the same reduced dose during the extension phase (without titration)

Fatigue, pain, and depression are assessed at baseline and then at weeks 4 and 8.

PROJECTED ACCRUAL: A total of 352 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 376 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Phase III Randomized Placebo-Controlled Trial to Determine Efficacy of Levocarnitine for Fatigue in Patients With Cancer
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4.	Dietary Supplement: levocarnitine; Given orally
Placebo Comparator: Arm II Patients receive oral placebo twice daily on weeks 1-4.	Other: placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. Mean Score Change in Fatigue Measured With Brief Fatigue Inventory From Baseline to 4 Weeks [assessed at baseline and 4 weeks after randomization]

   Fatigue was measured using Brief Fatigue Inventory (BFI). The average of all 9 items included in the scale (range: 0-10) was used to measure fatigue level, and a higher average represented worse fatigue. Score change= BFI score at 4 weeks - BFI score at baseline.

Secondary Outcome Measures

1. Mean Score Change in Fatigue Measured With FACIT-F From Baseline to 4 Weeks [assessed at baseline and 4 weeks after randomization]

   Fatigue was measured using Functional Assessment of Cancer Therapy- Fatigue subscale (FACIT-F). The sum of the scores for all 13 items (range: 0-52) included in the scale was used to measure fatigue level, and lower score represented worse fatigue. Score change= FACIT-F score at 4 weeks - FACIT-F score at baseline.

2. Mean Score Change in Depression Measured With CES-D Between 4 Weeks and Baseline [assessed at baseline and 4 weeks after randomization]

   Depression was measured using Center for Epidemiologic Studies Depression Scale (CES-D). The sum of the scores for all 20 items (range: 0-60) was used to assess depression level, and higher scores indicated a higher level of depression. Score change= CES-D score at 4 weeks - CES-D score at baseline.

3. Mean Score Change in Pain Measured With Brief Pain Inventory From Baseline to 4 Weeks [assessed at baseline and 4 weeks after randomization]

   Pain was measured using Brief Pain Inventory (BPI). The mean of the 4 severity items (range: 0-10 with 0 representing no pain and 10 representing pain as bad as you can imagine) was used to measure pain severity. Score change= BPI score at 4 weeks - BPI score at baseline.

4. Prevalence of Carnitine Deficiency at 4 Weeks [assessed at 4 weeks after randomization]

   Carnitine deficiency is defined as a ratio of acylcarnitine (total-free) to free carnitine > 0.4 μmol/L or free carnitine < 35 μmol/L for males and < 25 μmol/L for females.

5. Proportion of Patients With Stable or Improving Performance Status at 4 Weeks [assessed at baseline and 4 weeks after randomization]

   Performance status (PS) was measured using Eastern Cooperative Oncology Group performance status scale. Lower score represents better PS. Change in PS was calculated by PS at week 4- PS at baseline. Patients with negative value for change in PS were considered to have stable or improving PS.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of an invasive malignant disorder

• Moderate to severe fatigue within the past 4 weeks, defined as a score of ≥ 2 (on a scale of 0-4) on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) question "I feel fatigued"

• Age 18 and over

• Eastern Cooperative Oncology Group (ECOG) Performance status of 0-3

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after study participation

Exclusion Criteria:

• Brain metastases

• Hemoglobin < 9 g/dL, taken <=4 weeks prior to registration

• Severe, uncontrolled liver disease

• Evidence of severely compromised renal function including any 1 of the following:

• Renal failure

• End stage renal disease

• Ongoing renal dialysis

• Severe, uncontrolled cardiovascular disease

• Severe, uncontrolled pulmonary disease

• Pregnant or nursing

• History of seizures

• Known sensitivity to carnitine

• Delirium

• Nausea > grade 1

• Taking any form of levocarnitine (L-carnitine) supplementation or nutritional supplements containing carnitine within 2 months prior to registration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California	United States	94304
2	Stanford Comprehensive Cancer Center - Stanford	Stanford	California	United States	94305
3	Praxair Cancer Center at Danbury Hospital	Danbury	Connecticut	United States	06810
4	Manchester Memorial Hospital	Manchester	Connecticut	United States	06040
5	Lynn Regional Cancer Center at Boca Raton Community Hospital - Main Center	Boca Raton	Florida	United States	33486
6	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida	United States	32207
7	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60507
8	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
9	Graham Hospital	Canton	Illinois	United States	61520
10	Memorial Hospital	Carthage	Illinois	United States	62321
11	Eureka Community Hospital	Eureka	Illinois	United States	61530
12	Evanston Northwestern Healthcare - Evanston Hospital	Evanston	Illinois	United States	60201-1781
13	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
14	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
15	Mason District Hospital	Havana	Illinois	United States	62644
16	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
17	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
18	McDonough District Hospital	Macomb	Illinois	United States	61455
19	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
20	Community Cancer Center	Normal	Illinois	United States	61761
21	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
22	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
23	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
24	Proctor Hospital	Peoria	Illinois	United States	61614
25	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
26	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
27	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
28	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
29	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
30	Perry Memorial Hospital	Princeton	Illinois	United States	61356
31	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
32	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
33	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
34	Elkhart General Hospital	Elkhart	Indiana	United States	46515
35	Howard Community Hospital	Kokomo	Indiana	United States	46904
36	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
37	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
38	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
39	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
40	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
41	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
42	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
43	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
44	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
45	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
46	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
47	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
48	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
49	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
50	Hurley Medical Center	Flint	Michigan	United States	48503
51	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
52	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
53	Foote Hospital	Jackson	Michigan	United States	49201
54	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
55	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
56	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
57	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
58	Seton Cancer Institute - Saginaw	Saginaw	Michigan	United States	48601
59	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
60	St. John Macomb Hospital	Warren	Michigan	United States	48093
61	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
62	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
63	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
64	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
65	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
66	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
67	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
68	Park Nicollet Cancer Center	St. Louis Park	Minnesota	United States	55416
69	United Hospital	St. Paul	Minnesota	United States	55102
70	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
71	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey	United States	07018-1095
72	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
73	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York	United States	11209
74	Beth Israel Medical Center - Petrie Division	New York	New York	United States	10003-3803
75	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio	United States	44708
76	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
77	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
78	CCOP - Columbus	Columbus	Ohio	United States	43215
79	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
80	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
81	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
82	Grady Memorial Hospital	Delaware	Ohio	United States	43015
83	Fairfield Medical Center	Lancaster	Ohio	United States	43130
84	St. Rita's Medical Center	Lima	Ohio	United States	45801
85	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
86	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
87	Mercy Medical Center	Springfield	Ohio	United States	45504
88	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
89	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
90	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
91	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
92	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
93	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
94	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-0001
95	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
96	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
97	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301-1792
98	Albert Einstein Cancer Center	Philadelphia	Pennsylvania	United States	19141
99	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
100	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
101	Jennersville Regional Hospital	West Grove	Pennsylvania	United States	19390-9499
102	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
103	CCOP - MainLine Health	Wynnewood	Pennsylvania	United States	19096
104	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
105	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania	United States	17405
106	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
107	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
108	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
109	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
110	Dean Medical Center - Madison	Madison	Wisconsin	United States	53717
111	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
112	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
113	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
114	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
115	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin	United States	54868
116	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235

Sponsors and Collaborators

• ECOG-ACRIN Cancer Research Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Ricardo Cruciani, MD, PhD, Beth Israel Medical Center - Petrie Division
• Study Chair: Russell K. Portenoy, MD, Beth Israel Medical Center - Petrie Division

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ECOG-ACRIN Cancer Research Group
• ClinicalTrials.gov Identifier: NCT00091169
• Other Study ID Numbers: E4Z02; E4Z02; U10CA023318; CDR0000384087
• First Posted: Sep 8, 2004
• Last Update Posted: May 30, 2016
• Last Verified: May 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by ECOG-ACRIN Cancer Research Group: fatigue; unspecified adult solid tumor, protocol specific; levocarnitine; depression; pain; carnitine deficiency
• Additional relevant MeSH terms: Fatigue

Study Results

Participant Flow

Recruitment Details	This study was activated on 11/3/2005, suspended on 5/4/2006 after reaching its original accrual goal (160 eligible patients), reactivated on 9/6/2006 after the accrual target amendment (286 eligible patients) was approved, and closed on 1/23/2007 with a total accrual of 376 patients.

Arm/Group Title	Levocarnitine	Placebo
Arm/Group Description	Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4. levocarnitine: Given orally	Patients receive oral placebo twice daily on weeks 1-4. placebo: Given orally
Period Title: Overall Study
STARTED	189	187
Treated	163	170
COMPLETED	132	134
NOT COMPLETED	57	53

Baseline Characteristics

Arm/Group Title	Levocarnitine	Placebo	Total
Arm/Group Description	Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4. levocarnitine: Given orally	Patients receive oral placebo twice daily on weeks 1-4. placebo: Given orally	Total of all reporting groups
Overall Participants	189	187	376
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64	62	63
Sex: Female, Male (Count of Participants)
Female	111 58.7%	79 42.2%	190 50.5%
Male	78 41.3%	108 57.8%	186 49.5%

Outcome Measures

1. Primary Outcome

Title	Mean Score Change in Fatigue Measured With Brief Fatigue Inventory From Baseline to 4 Weeks
Description	Fatigue was measured using Brief Fatigue Inventory (BFI). The average of all 9 items included in the scale (range: 0-10) was used to measure fatigue level, and a higher average represented worse fatigue. Score change= BFI score at 4 weeks - BFI score at baseline.
Time Frame	assessed at baseline and 4 weeks after randomization

Outcome Measure Data

Analysis Population Description

All randomized patients

Arm/Group Title	Levocarnitine	Placebo
Arm/Group Description	Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4. levocarnitine: Given orally	Patients receive oral placebo twice daily on weeks 1-4. placebo: Given orally
Measure Participants	189	187
Mean (95% Confidence Interval) [units on a scale]	-0.96	-1.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levocarnitine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Mean Score Change in Fatigue Measured With FACIT-F From Baseline to 4 Weeks
Description	Fatigue was measured using Functional Assessment of Cancer Therapy- Fatigue subscale (FACIT-F). The sum of the scores for all 13 items (range: 0-52) included in the scale was used to measure fatigue level, and lower score represented worse fatigue. Score change= FACIT-F score at 4 weeks - FACIT-F score at baseline.
Time Frame	assessed at baseline and 4 weeks after randomization

Outcome Measure Data

Analysis Population Description

All randomized patients who reported FACIT-F score at both baseline and 4 weeks

Arm/Group Title	Levocarnitine	Placebo
Arm/Group Description	Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4. levocarnitine: Given orally	Patients receive oral placebo twice daily on weeks 1-4. placebo: Given orally
Measure Participants	145	139
Mean (95% Confidence Interval) [units on a scale]	5.36	4.04

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levocarnitine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Mean Score Change in Depression Measured With CES-D Between 4 Weeks and Baseline
Description	Depression was measured using Center for Epidemiologic Studies Depression Scale (CES-D). The sum of the scores for all 20 items (range: 0-60) was used to assess depression level, and higher scores indicated a higher level of depression. Score change= CES-D score at 4 weeks - CES-D score at baseline.
Time Frame	assessed at baseline and 4 weeks after randomization

Outcome Measure Data

Analysis Population Description

All randomized patients who reported CES-D score at both baseline and 4 weeks

Arm/Group Title	Levocarnitine	Placebo
Arm/Group Description	Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4. levocarnitine: Given orally	Patients receive oral placebo twice daily on weeks 1-4. placebo: Given orally
Measure Participants	145	139
Mean (95% Confidence Interval) [units on a scale]	-3.05	-2.91

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levocarnitine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Mean Score Change in Pain Measured With Brief Pain Inventory From Baseline to 4 Weeks
Description	Pain was measured using Brief Pain Inventory (BPI). The mean of the 4 severity items (range: 0-10 with 0 representing no pain and 10 representing pain as bad as you can imagine) was used to measure pain severity. Score change= BPI score at 4 weeks - BPI score at baseline.
Time Frame	assessed at baseline and 4 weeks after randomization

Outcome Measure Data

Analysis Population Description

All randomized patients who reported BPI score at both baseline and 4 weeks

Arm/Group Title	Levocarnitine	Placebo
Arm/Group Description	Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4. levocarnitine: Given orally	Patients receive oral placebo twice daily on weeks 1-4. placebo: Given orally
Measure Participants	133	138
Mean (95% Confidence Interval) [units on a scale]	-0.19	-0.08

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levocarnitine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Prevalence of Carnitine Deficiency at 4 Weeks
Description	Carnitine deficiency is defined as a ratio of acylcarnitine (total-free) to free carnitine > 0.4 μmol/L or free carnitine < 35 μmol/L for males and < 25 μmol/L for females.
Time Frame	assessed at 4 weeks after randomization

Outcome Measure Data

Analysis Population Description

All randomized patients who had carnitine data at 4 weeks

Arm/Group Title	Arm I	Arm II
Arm/Group Description	Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4. levocarnitine: Given orally	Patients receive oral placebo twice daily on weeks 1-4. placebo: Given orally
Measure Participants	133	132
Number (95% Confidence Interval) [proportion of participants]	0.113 0.1%	0.333 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levocarnitine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.00001
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Proportion of Patients With Stable or Improving Performance Status at 4 Weeks
Description	Performance status (PS) was measured using Eastern Cooperative Oncology Group performance status scale. Lower score represents better PS. Change in PS was calculated by PS at week 4- PS at baseline. Patients with negative value for change in PS were considered to have stable or improving PS.
Time Frame	assessed at baseline and 4 weeks after randomization

Outcome Measure Data

Analysis Population Description

All randomized patients who had performance status data at baseline and 4 weeks

Arm/Group Title	Arm I	Arm II
Arm/Group Description	Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4. levocarnitine: Given orally	Patients receive oral placebo twice daily on weeks 1-4. placebo: Given orally
Measure Participants	155	160
Number (95% Confidence Interval) [proportion of participants]	0.806 0.4%	0.875 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levocarnitine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.677
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Arm/Group Title	Levocarnitine		Placebo
Arm/Group Description	Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4. levocarnitine: Given orally		Patients receive oral placebo twice daily on weeks 1-4. placebo: Given orally
All Cause Mortality
	Levocarnitine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Levocarnitine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/166 (4.8%)		8/171 (4.7%)
Blood and lymphatic system disorders
Anemia	0/166 (0%)		1/171 (0.6%)
Cardiac disorders
Atrial fibrillation	0/166 (0%)		1/171 (0.6%)
Gastrointestinal disorders
Constipation	1/166 (0.6%)		0/171 (0%)
Diarrhea w/o prior colostomy	1/166 (0.6%)		3/171 (1.8%)
Nausea	2/166 (1.2%)		2/171 (1.2%)
Vomiting	1/166 (0.6%)		1/171 (0.6%)
Abdomen, pain	0/166 (0%)		1/171 (0.6%)
General disorders
Fatigue	2/166 (1.2%)		0/171 (0%)
Infections and infestations
Infection w/ unk ANC urinary tract NOS	1/166 (0.6%)		0/171 (0%)
Investigations
Platelets decreased	0/166 (0%)		1/171 (0.6%)
Metabolism and nutrition disorders
Anorexia	0/166 (0%)		1/171 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death - disease progression NOS	1/166 (0.6%)		2/171 (1.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/166 (1.2%)		0/171 (0%)
Skin and subcutaneous tissue disorders
Pruritus/itching	1/166 (0.6%)		0/171 (0%)
Rash/desquamation	1/166 (0.6%)		0/171 (0%)
Other (Not Including Serious) Adverse Events
	Levocarnitine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/166 (6%)		9/171 (5.3%)
Blood and lymphatic system disorders
Anemia	10/166 (6%)		9/171 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.