2CARE: Coenzyme Q10 in Huntington's Disease (HD)

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00608881
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS) (NIH), University of Rochester (Other)
• Enrollment: 609
• Locations: 49
• Arms: 2
• Duration (Months): 86
• Patients Per Site: 12.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The goals of this trial are to determine if coenzyme Q10 is effective in slowing the worsening symptoms of Huntington's disease and to learn about the safety and acceptability of long-term coenzyme Q10 use by determining its effects on people with Huntington's disease.

Condition or Disease	Intervention/Treatment	Phase
Huntington's Disease	Drug: coenzyme Q10; Other: placebo	Phase 3

Detailed Description

Huntington's disease (HD) is a slowly progressive disorder that devastates the lives of those affected and their families. There are no treatments that slow the progression of HD, only mildly effective symptomatic therapies are available.

The purpose of this trial is to find out if coenzyme Q10 (CoQ) is effective in slowing the worsening symptoms of HD. In this study, researchers also will learn about the safety and acceptability of long-term CoQ use by determining its effects on people with HD.

Participants in this trial will be randomly chosen to one of two groups. Group 1 will receive CoQ (2400 mg/day), and group 2 will receive a placebo (an inactive substance). Researchers will compare the change in total functional capacity (TFC)-a measure of functional disability-in the two groups. The TFC is a valid and reliable measure of disease progression and is particularly responsive to change in the early and mid-stages of HD. Researchers will also compare the changes in other components of the Unified Huntington's Disease Rating Scale '99 (UHDRS) including: the total motor score, total behavioral frequency score, total behavior frequency X severity score, verbal fluency test, symbol digit modalities test, Stroop, interference test, functional checklist, and independence scale scores. The groups will also be compared with respect to tolerability, adverse events, vital signs, and laboratory test results as measures of safety.

Study Design

• Study Type: Interventional
• Actual Enrollment: 609 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Coenzyme Q10 in Huntington's Disease (HD)
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A - coenzyme Q10 2400 mg/day Randomized to active treatment (coenzyme Q10 2400 mg/day)	Drug: coenzyme Q10; 4 - 300 mg CoQ chewable wafers taken orally twice a day; Other Names: CoQ
Placebo Comparator: B - Placebo Randomized to placebo	Other: placebo; an inactive substance

Outcome Measures

Primary Outcome Measures

1. Joint Rank (Combination of Time to Death (for Subjects Who Died) and Change in Total Functional Capacity Score (TFC) From Baseline to Month 60 (for Subjects Who Survived)) [5 years]

   The primary outcome variable at the start of the trial was the change in TFC score from baseline to Month 60. The Data and Safety Monitoring Board recommended to the trial leadership that they reconsider how they accommodate missing data from subjects who die in their primary analysis of the change in TFC score. Based on these recommendations, the trial leadership changed the primary analysis to that of a joint rank approach. TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).

Secondary Outcome Measures

1. Change in Total Functional Capacity (TFC) Score From Baseline to Month 60 [Baseline and Month 60]

   TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).

2. Change in Functional Checklist Score From Baseline to Month 60 [Baseline and Month 60]

   The functional assessment checklist includes 25 questions about common daily tasks. A score of 1 is given for each "yes" reply and a score of 0 is given for each "no" reply (scale range is 0-25). Higher scores indicate better functioning.

3. Change in Independence Scale Score From Baseline to Month 60 [Baseline and Month 60]

   The independence scale assesses independence on a 0 to 100 scale with higher scores indicating better functioning.

4. Change in Total Motor Score From Baseline to Month 60 [Baseline and Month 60]

   The motor section of the Unified Huntington's Disease Rating Scale (UHDRS) assesses motor features of Huntington disease with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural stability. The total motor score is the sum of all the individual motor ratings, with higher scores (124) indicating more severe motor impairment than lower scores. The score ranges from 0 to 124.

5. Change in Behavioral Frequency Score From Baseline to Month 60 [Baseline and Month 60]

   The Unified Huntington's Disease Rating Scale (UHDRS) behavioral subscale assesses frequency and severity of psychiatric-related symptoms, including depressed mood, apathy, low self-esteem/guilt, suicidal thoughts, anxiety, irritable behavior, aggressive behavior, obsessional thinking, compulsive behavior, delusions, and hallucinations. A total score was calculated by summing up all the individual behavioral frequency items (range 0-56) with higher scores representing more severe behavioral impairment.

6. Change in Behavioral Frequency x Severity Score From Baseline to Month 60 [Baseline and Month 60]

   The Unified Huntington's Disease Rating Scale (UHDRS) behavioral subscale assesses frequency and severity of psychiatric-related symptoms, including depressed mood, apathy, low self-esteem/guilt, suicidal thoughts, anxiety, irritable behavior, aggressive behavior, obsessional thinking, compulsive behavior, delusions, and hallucinations. The total score is the sum of the product of the individual behavioral frequency and severity items (range 0-176) with higher scores representing more severe behavioral impairment.

7. Change in Symbol Digit Modalities Test (SDMT) From Baseline to Month 60 [Baseline and Month 60]

   The SDMT assesses attention, visuoperceptual processing, working memory, and cognitive/psychomotor speed. The score is the number of correctly paired abstract symbols and specific numbers in 90 seconds with higher scores indicating better cognitive functioning.

8. Change in Verbal Fluency Test From Baseline to Month 60 [Baseline and Month 60]

   The verbal fluency test is typically considered a measure of executive function. The score is the number of correct words produced across three 1-minute trials.

9. Change in Stroop Interference Test - Color Naming From Baseline to Month 60 [Baseline and Month 60]

   Stroop Interference Test - color naming score is the total number of correct colors identified in 45 seconds and reflects processing speed.

10. Change in Stroop Interference Test - Word Reading From Baseline to Month 60 [Baseline and Month 60]

    Stroop Interference Test - word reading score is the total number of correct words read in 45 seconds and reflects processing speed.

11. Change in Stroop Interference Test - Interference From Baseline to Month 60 [Baseline and Month 60]

    Stroop Interference Test - interference score is the total number of correct items identified in 45 seconds and reflects an executive measure of inhibitory ability.

12. Time to a Two-Point Decline in TFC Score or Death [5 years]

    TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).

13. Time to a Three-Point Decline in TFC Score or Death [5 years]

    TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).

14. Number Completing Study at Assigned Dosage Level [5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

To be eligible for enrollment into this study, subjects must meet the following eligibility criteria within 28 days prior to randomization:

• Subjects must have clinical features of HD and a confirmed family history of HD, OR a CAG repeat expansion ≥ 36.

• TFC > 9.

• Must be ambulatory and not require skilled nursing care.

• Age ≥ 16 years.

• Women must not be able to become pregnant (e.g., post menopausal, surgically sterile or using adequate birth control methods for the duration of the study).

• If psychotropic medications are taken (e.g., anxiolytics, hypnotics, benzodiazepines, antidepressants), they must be at a stable dosage for four weeks prior to randomization and should be maintained at a constant dosage throughout the study, as possible. (Note: stable dosing of tetrabenazine is allowable.) Any changes to these medications mandated by clinical conditions will be systematically recorded and the subject will be permitted to remain in the trial.

• Able to give informed consent and comply with trial procedures

• Able to take oral medication.

• May be required to identify an informant or caregiver who will be willing and able to supervise the daily dosing of study medications and to maintain control of study medications in the home.

• A designated individual will be identified by the subject to participate in the ongoing consent process should the subject's cognitive capacity to consent become compromised during participation in the study.

Exclusion Criteria:

• History or known sensitivity of intolerability to CoQ.

• Exposure to any investigational drug within 30 days of the Baseline visit.

• Clinical evidence of unstable medical illness in the investigator's judgment.

• Unstable psychiatric illness defined as psychosis (hallucinations or delusions), untreated major depression or suicidal ideation within 90 days of the Baseline visit.

• Substance (alcohol or drug) abuse within one year of the Baseline visit.

• Women who are pregnant or breastfeeding.

• Use of supplemental coenzyme Q10 within 30 days prior to the Baseline visit

• Clinically serious abnormalities in the screening laboratory studies (Screening creatinine greater than 2.0, alanine aminotransferase (ALT) or total bilirubin greater than 3 times the upper limit of normal, absolute neutrophil count of ≤1000/ul, platelet concentration of <100,000/ul, hematocrit level of <33 for female or <35 for male, or coagulation tests > 1.5 time upper limit of normal).

• Known allergy to FD&C yellow #5 or any other ingredient in the study drug (active and placebo)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama At Birmingham, Pediatric Neurology Childrens, Harbor Bldg Suite 314, 1600 7Th Avenue South	Birmingham	Alabama	United States	35233-1711
2	Mayo Clinic Arizona, 13400 East Shea Boulevard, Csu-Cp21B	Scottsdale	Arizona	United States	85259
3	WASHINGTON REGIONAL MEDICAL CENTER, 3215 N. North Hills Blvd	Fayetteville	Arkansas	United States	72703
4	University of California Irvine, Department of Neurology, 100 Irvine Hall	Irvine	California	United States	92697-4275
5	University of California Davis, Medical Center Dept of Neurology, Acc Building Suite 3700, 4860 Y Street	Sacramento	California	United States	95817
6	Colorado Neurological Institute, Movement Disorders Center, 701 East Hampden Avenue Suite 510	Littleton	Colorado	United States	80120
7	University of Florida Center for Movement Disorders and Neurorestoration, 3450 Hull Road, 4th Floor	Gainesville	Florida	United States	32607
8	UNIVERSITY OF MIAMI, 1150 NW 14th STREET, #401	Miami	Florida	United States	33136
9	University of South Florida, College of Medicine Dept of Neurology, 12901 Bruce B Downs Blvd Mdc-55	Tampa	Florida	United States	33612
10	Emory University, Wesley Woods Center, 1841 Clifton Road NE Room 314	Atlanta	Georgia	United States	30329
11	Idaho Elks Rehabilitation Hospital, 600 North Robbins Road	Boise	Idaho	United States	83702
12	Rush University Medical Center, Department of Neurological Sciences, 1725 West Harrison Suite 755	Chicago	Illinois	United States	60612
13	Indiana University School of Medicine, Outpatient Clinical Research Facility, 535 Barnhill Drive Room #150	Indianapolis	Indiana	United States	46202
14	University of Iowa Hospital and Clinics, 200 Hawkins Road, Room W263 General Hospital	Iowa City	Iowa	United States	52242-1000
15	University of Kansas Medical Center, Department of Neurology, 3599 Rainbow Blvd Mail Stop 2012	Kansas City	Kansas	United States	66160-7314
16	Hereditary Neurological Disease Centre (Hndc),3223 N. Webb, Suite 4	Wichita	Kansas	United States	67226
17	University of Maryland School of Medicine, 22 South Greene Street, N4 W49-B	Baltimore	Maryland	United States	21201
18	Johns Hopkins University, 600 North Wolfe Street, Meyer 2-181	Baltimore	Maryland	United States	21287
19	Boston University School of Medicine, Department of Neurology, 715 Albany Street C329	Boston	Massachusetts	United States	02118
20	Massachusetts General Hospital, 149 13Th Street Suite 2241	Charlestown	Massachusetts	United States	02129
21	University of Michigan, 1500 E Medical Center Drive, B1 H202 Nuclear Medicine	Ann Arbor	Michigan	United States	48109-0028
22	Struthers Parkinson'S Center, 6701 Country Club Drive	Golden Valley	Minnesota	United States	55427
23	Washington University School of Medicine, Box 8111, 660 South Euclid	St Louis	Missouri	United States	63110
24	University of Las Vegas School of Medicine, 1707 W. Charleston Blvd, Suite 220	Las Vegas	Nevada	United States	89102
25	Cooper University Hospital	Camden	New Jersey	United States	08103
26	Nj Neuroscience Institute, Jfk Medical Center, 65 James Street	Edison	New Jersey	United States	08818
27	Albany Medical College, Parkinson'S Disease & Movement Disorders Ctr	Albany	New York	United States	12208
28	North Shore-Lij Health System, 350 Community Drive Room 110, Research Institute	Manhasset	New York	United States	11030
29	Columbia University, Sergievsky Center P&S Box 16, 630 West 168Th Street	New York	New York	United States	10032
30	University of Rochester, Department of Neurology, 919 Westfall Road Building C Suite 220	Rochester	New York	United States	14618
31	Duke University, 932 Morreene Road #213	Durham	North Carolina	United States	27705
32	Wake Forest University, Baptist Med Center, Department of Neurology, Medical Center Boulevard	Winston Salem	North Carolina	United States	27157
33	University of Cincinnati/Cincinnati Children'S Hospital, 222 Piedmont Avenue, Suite 3200	Cincinnati	Ohio	United States	45219
34	OHIO STATE UNIVERSITY , 2006 Kenny Road	Columbus	Ohio	United States	43212
35	ST. LUKE'S HOSPITAL, 240 Centronia Road	Allentown	Pennsylvania	United States	18104
36	University of Pennsylvania, Pennsylvania Hospital Department of Neurology , 330 South 9Th Street	Philadelphia	Pennsylvania	United States	19107
37	University of Pittsburgh Kaufmann Medical Building, 3471 Fifth Avunue, Suite 811	Pittsburgh	Pennsylvania	United States	15213
38	BUTLER HOSPTIAL MOVEMENT DISORDER PROGRAM, 345 Blackstone Boulevard	Providence	Rhode Island	United States	02906
39	The University of Tennesee Health Science Cen, 855 Monroe Avenue, Department of Neurology, Room 415 Link Bldg	Memphis	Tennessee	United States	38163
40	UN oF TEXAS SOUTHWESTERN MED CENTER DALLAS, 5323 HARRY HINES BOULEVARD H1.108	Dallas	Texas	United States	75390-9016
41	Baylor College of Medicine, 6550 Fannin Suite 1801	Houston	Texas	United States	77030
42	Westmead Hospital, Department of Neurology Level 1, Po Box 533	Wentworthville	New South Wales	Australia	2145
43	University of Calgary, Heritage Medical Research Clinic, Trw Bldg 5 Floor, 3280 Hospital Dri. NW	Calgary	Alberta	Canada	T2N 4Z6
44	University of Alberta, Glenrose Rehab Hosp, Movement Disorder Clinic , Rm 0601 Gleneast 10230 - 111 Avenue	Edmonton	Alberta	Canada	T5G 0B7
45	Department of Medical Genetics, Ubc Hospital, Room S179-2211 Westbrook Mall	Vancouver	British Columbia	Canada	V6T 2B5
46	London Health Sciences Centre, University Hospital, 339 Windermere Road	London	Ontario	Canada	N6A 5A5
47	Centre For Movement Disorders, 2780 Bur Oak Avenue	Markham	Ontario	Canada	L4A 1G8
48	NORTH YORK GENERAL HOSPITAL (2), 4001 Leslie Street	Toronto	Ontario	Canada	M2K 1E1
49	North York General Hospital, 4001 Leslie Street	Toronto	Ontario	Canada	M2R 1N5

Sponsors and Collaborators

• Massachusetts General Hospital
• National Institute of Neurological Disorders and Stroke (NINDS)
• University of Rochester

Investigators

• Principal Investigator: Merit Cudkowicz, MD MSc, Massachusetts General Hospital
• Principal Investigator: Michael McDermott, PhD, University of Rochester, Biostatistics
• Principal Investigator: Karl Kieburtz, MD MPH, Director, Clinical Trials Coordination Center, University of Rochester

Study Documents (Full-Text)

None provided.

More Information

Publications

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• Responsible Party: Merit E. Cudkowicz, MD, Julieanne Dorn Professor of Neurology, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00608881
• Other Study ID Numbers: 2CARE 01.00; 5U01NS052592; 5R01NS052619
• First Posted: Feb 6, 2008
• Last Update Posted: Mar 30, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Merit E. Cudkowicz, MD, Julieanne Dorn Professor of Neurology, Massachusetts General Hospital: Huntington's disease; Huntington disease; HD; coenzyme Q10; CoQ
• Additional relevant MeSH terms: Huntington Disease; Ubiquinone; Coenzyme Q10

Study Results

Participant Flow

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Period Title: Overall Study
STARTED	303	306
COMPLETED	224	240
NOT COMPLETED	79	66

Baseline Characteristics

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo	Total
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance	Total of all reporting groups
Overall Participants	303	306	609
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.5 (11.9)	50.7 (11.6)	50.6 (11.7)
Sex: Female, Male (Count of Participants)
Female	149 49.2%	164 53.6%	313 51.4%
Male	154 50.8%	142 46.4%	296 48.6%

Outcome Measures

1. Primary Outcome

Title	Joint Rank (Combination of Time to Death (for Subjects Who Died) and Change in Total Functional Capacity Score (TFC) From Baseline to Month 60 (for Subjects Who Survived))
Description	The primary outcome variable at the start of the trial was the change in TFC score from baseline to Month 60. The Data and Safety Monitoring Board recommended to the trial leadership that they reconsider how they accommodate missing data from subjects who die in their primary analysis of the change in TFC score. Based on these recommendations, the trial leadership changed the primary analysis to that of a joint rank approach. TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Mean (Standard Deviation) [rank]	303.3 (173.1)	306.7 (179.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	In this joint rank analysis, subjects are ranked from worst to best outcome with subjects who die being assigned the worst ranks (and ranked according to the time of death) and subjects who survive being ranked more favorably in the order of the change from baseline to Month 60 in TFC score.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	π hat
	Estimated Value	0.494
	Confidence Interval	(2-Sided) 95%; 0.454 to 0.534
	Parameter Dispersion	Type: Value:
	Estimation Comments	π hat is the estimate of the probability π that a randomly selected subject treated with CoQ has a better outcome than a randomly selected subject treated with placebo. Under the null hypothesis of no effect of CoQ, π = 0.50.

2. Secondary Outcome

Title	Change in Total Functional Capacity (TFC) Score From Baseline to Month 60
Description	TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Least Squares Mean (Standard Error) [units on a scale]	-4.53 (0.25)	-4.76 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.23
	Confidence Interval	(2-Sided) 95%; -0.44 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in Functional Checklist Score From Baseline to Month 60
Description	The functional assessment checklist includes 25 questions about common daily tasks. A score of 1 is given for each "yes" reply and a score of 0 is given for each "no" reply (scale range is 0-25). Higher scores indicate better functioning.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Mean (Standard Error) [units on a scale]	-7.93 (0.55)	-8.02 (0.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -1.40 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change in Independence Scale Score From Baseline to Month 60
Description	The independence scale assesses independence on a 0 to 100 scale with higher scores indicating better functioning.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Mean (Standard Error) [units on a scale]	-26.30 (1.92)	-24.86 (1.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.44
	Confidence Interval	(2-Sided) 95%; -6.68 to 3.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change in Total Motor Score From Baseline to Month 60
Description	The motor section of the Unified Huntington's Disease Rating Scale (UHDRS) assesses motor features of Huntington disease with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural stability. The total motor score is the sum of all the individual motor ratings, with higher scores (124) indicating more severe motor impairment than lower scores. The score ranges from 0 to 124.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Least Squares Mean (Standard Error) [units on a scale]	18.06 (1.22)	19.18 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.12
	Confidence Interval	(2-Sided) 95%; -4.40 to 2.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change in Behavioral Frequency Score From Baseline to Month 60
Description	The Unified Huntington's Disease Rating Scale (UHDRS) behavioral subscale assesses frequency and severity of psychiatric-related symptoms, including depressed mood, apathy, low self-esteem/guilt, suicidal thoughts, anxiety, irritable behavior, aggressive behavior, obsessional thinking, compulsive behavior, delusions, and hallucinations. A total score was calculated by summing up all the individual behavioral frequency items (range 0-56) with higher scores representing more severe behavioral impairment.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Least Squares Mean (Standard Error) [units on a scale]	1.39 (0.55)	1.43 (0.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -1.48 to 1.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change in Behavioral Frequency x Severity Score From Baseline to Month 60
Description	The Unified Huntington's Disease Rating Scale (UHDRS) behavioral subscale assesses frequency and severity of psychiatric-related symptoms, including depressed mood, apathy, low self-esteem/guilt, suicidal thoughts, anxiety, irritable behavior, aggressive behavior, obsessional thinking, compulsive behavior, delusions, and hallucinations. The total score is the sum of the product of the individual behavioral frequency and severity items (range 0-176) with higher scores representing more severe behavioral impairment.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Least Squares Mean (Standard Error) [units on a scale]	4.29 (1.52)	5.06 (1.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95%; -4.78 to 3.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change in Symbol Digit Modalities Test (SDMT) From Baseline to Month 60
Description	The SDMT assesses attention, visuoperceptual processing, working memory, and cognitive/psychomotor speed. The score is the number of correctly paired abstract symbols and specific numbers in 90 seconds with higher scores indicating better cognitive functioning.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Least Squares Mean (Standard Error) [units on a scale]	-10.95 (0.66)	-11.36 (0.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95%; -1.32 to 2.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change in Verbal Fluency Test From Baseline to Month 60
Description	The verbal fluency test is typically considered a measure of executive function. The score is the number of correct words produced across three 1-minute trials.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Least Squares Mean (Standard Error) [units on a scale]	-5.07 (0.79)	-4.47 (0.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -2.71 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change in Stroop Interference Test - Color Naming From Baseline to Month 60
Description	Stroop Interference Test - color naming score is the total number of correct colors identified in 45 seconds and reflects processing speed.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Least Squares Mean (Standard Error) [units on a scale]	-14.21 (1.00)	-14.51 (0.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 95%; -2.28 to 2.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change in Stroop Interference Test - Word Reading From Baseline to Month 60
Description	Stroop Interference Test - word reading score is the total number of correct words read in 45 seconds and reflects processing speed.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Least Squares Mean (Standard Error) [units on a scale]	-15.25 (1.36)	-19.13 (1.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.88
	Confidence Interval	(2-Sided) 95%; 0.31 to 7.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change in Stroop Interference Test - Interference From Baseline to Month 60
Description	Stroop Interference Test - interference score is the total number of correct items identified in 45 seconds and reflects an executive measure of inhibitory ability.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Least Squares Mean (Standard Error) [units on a scale]	-7.57 (0.81)	-8.61 (0.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; -1.10 to 3.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Time to a Two-Point Decline in TFC Score or Death
Description	TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Median (95% Confidence Interval) [days to event]	553	549

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Time to a Three-Point Decline in TFC Score or Death
Description	TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Median (95% Confidence Interval) [days to event]	917	911

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Number Completing Study at Assigned Dosage Level
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Measure Participants	303	306
Number [participants completing study on drug]	98 32.3%	108 35.3%

Adverse Events

Time Frame	5 years
Adverse Event Reporting Description	Adverse events were assessed at each visit by recording all voluntary complaints of the subject and by assessment of clinical features. Subjects were questioned regarding the occurrence of any adverse event since the last visit. All adverse events were recorded on an Adverse Event Log case report form.
Arm/Group Title	A - Coenzyme Q10 2400 mg/Day		B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day		Randomized to placebo placebo: an inactive substance
All Cause Mortality
	A - Coenzyme Q10 2400 mg/Day		B - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	A - Coenzyme Q10 2400 mg/Day		B - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/303 (25.1%)		83/306 (27.1%)
Blood and lymphatic system disorders
NEUTROPENIA	1/303 (0.3%)		0/306 (0%)
Cardiac disorders
ANGINA UNSTABLE	0/303 (0%)		1/306 (0.3%)
ATRIAL FIBRILLATION	1/303 (0.3%)		0/306 (0%)
CARDIAC ARREST	0/303 (0%)		1/306 (0.3%)
CORONARY ARTERY DISEASE	0/303 (0%)		1/306 (0.3%)
CORONARY ARTERY OCCLUSION	1/303 (0.3%)		0/306 (0%)
MYOCARDIAL INFARCTION	0/303 (0%)		3/306 (1%)
Congenital, familial and genetic disorders
HUNTINGTON'S DISEASE	2/303 (0.7%)		2/306 (0.7%)
Ear and labyrinth disorders
VERTIGO	0/303 (0%)		1/306 (0.3%)
Eye disorders
RETINAL DETACHMENT	0/303 (0%)		1/306 (0.3%)
Gastrointestinal disorders
COLITIS	0/303 (0%)		1/306 (0.3%)
CROHN'S DISEASE	0/303 (0%)		1/306 (0.3%)
DIARRHOEA	1/303 (0.3%)		0/306 (0%)
DYSPHAGIA	2/303 (0.7%)		2/306 (0.7%)
HAEMORRHOIDS	1/303 (0.3%)		0/306 (0%)
INTESTINAL OBSTRUCTION	1/303 (0.3%)		1/306 (0.3%)
LARGE INTESTINAL OBSTRUCTION	1/303 (0.3%)		0/306 (0%)
PEPTIC ULCER	1/303 (0.3%)		0/306 (0%)
SMALL INTESTINAL OBSTRUCTION	1/303 (0.3%)		0/306 (0%)
VOMITING	1/303 (0.3%)		0/306 (0%)
General disorders
CHEST PAIN	2/303 (0.7%)		0/306 (0%)
DRUG WITHDRAWAL SYNDROME	0/303 (0%)		1/306 (0.3%)
NON-CARDIAC CHEST PAIN	1/303 (0.3%)		0/306 (0%)
Hepatobiliary disorders
CHOLECYSTITIS	1/303 (0.3%)		1/306 (0.3%)
CHOLELITHIASIS	1/303 (0.3%)		0/306 (0%)
Immune system disorders
DRUG HYPERSENSITIVITY	0/303 (0%)		1/306 (0.3%)
Infections and infestations
ABSCESS	1/303 (0.3%)		0/306 (0%)
ARTHRITIS INFECTIVE	0/303 (0%)		1/306 (0.3%)
BACTERAEMIA	0/303 (0%)		1/306 (0.3%)
CELLULITIS	0/303 (0%)		1/306 (0.3%)
DIVERTICULITIS	0/303 (0%)		2/306 (0.7%)
GASTROENTERITIS	0/303 (0%)		1/306 (0.3%)
NECROTISING FASCIITIS	1/303 (0.3%)		0/306 (0%)
PNEUMONIA	2/303 (0.7%)		5/306 (1.6%)
SEPSIS	1/303 (0.3%)		0/306 (0%)
SKIN GRAFT INFECTION	0/303 (0%)		1/306 (0.3%)
STAPHYLOCOCCAL BACTERAEMIA	1/303 (0.3%)		0/306 (0%)
STAPHYLOCOCCAL INFECTION	1/303 (0.3%)		0/306 (0%)
URINARY TRACT INFECTION	0/303 (0%)		2/306 (0.7%)
Injury, poisoning and procedural complications
ACCIDENTAL OVERDOSE	1/303 (0.3%)		1/306 (0.3%)
ANKLE FRACTURE	1/303 (0.3%)		1/306 (0.3%)
COMMINUTED FRACTURE	1/303 (0.3%)		0/306 (0%)
CONCUSSION	0/303 (0%)		1/306 (0.3%)
FACIAL BONES FRACTURE	0/303 (0%)		1/306 (0.3%)
FALL	3/303 (1%)		5/306 (1.6%)
FEMUR FRACTURE	1/303 (0.3%)		0/306 (0%)
FIBULA FRACTURE	1/303 (0.3%)		0/306 (0%)
FRACTURE	2/303 (0.7%)		0/306 (0%)
HIP FRACTURE	1/303 (0.3%)		2/306 (0.7%)
INJURY	1/303 (0.3%)		0/306 (0%)
INTENTIONAL OVERDOSE	1/303 (0.3%)		0/306 (0%)
LIMB TRAUMATIC AMPUTATION	1/303 (0.3%)		0/306 (0%)
ROAD TRAFFIC ACCIDENT	1/303 (0.3%)		1/306 (0.3%)
SPINAL COMPRESSION FRACTURE	0/303 (0%)		1/306 (0.3%)
SUBDURAL HAEMATOMA	1/303 (0.3%)		5/306 (1.6%)
TIBIA FRACTURE	1/303 (0.3%)		0/306 (0%)
TRAUMATIC FRACTURE	0/303 (0%)		1/306 (0.3%)
UPPER LIMB FRACTURE	0/303 (0%)		1/306 (0.3%)
WRIST FRACTURE	1/303 (0.3%)		0/306 (0%)
Metabolism and nutrition disorders
DEHYDRATION	1/303 (0.3%)		1/306 (0.3%)
DIABETIC KETOACIDOSIS	1/303 (0.3%)		0/306 (0%)
HYPERGLYCAEMIA	0/303 (0%)		1/306 (0.3%)
HYPONATRAEMIA	1/303 (0.3%)		0/306 (0%)
Musculoskeletal and connective tissue disorders
NECK PAIN	0/303 (0%)		2/306 (0.7%)
NOSE DEFORMITY	0/303 (0%)		1/306 (0.3%)
OSTEOARTHRITIS	0/303 (0%)		1/306 (0.3%)
OSTEOPOROSIS	1/303 (0.3%)		0/306 (0%)
RHABDOMYOLYSIS	1/303 (0.3%)		0/306 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA	0/303 (0%)		1/306 (0.3%)
BRAIN NEOPLASM	1/303 (0.3%)		0/306 (0%)
BREAST CANCER	1/303 (0.3%)		2/306 (0.7%)
CARCINOID TUMOUR	1/303 (0.3%)		0/306 (0%)
COLON CANCER METASTATIC	0/303 (0%)		1/306 (0.3%)
GLIOMA	1/303 (0.3%)		0/306 (0%)
INFLAMMATORY CARCINOMA OF THE BREAST	0/303 (0%)		1/306 (0.3%)
LUNG NEOPLASM MALIGNANT	1/303 (0.3%)		1/306 (0.3%)
MANTLE CELL LYMPHOMA	0/303 (0%)		1/306 (0.3%)
PROSTATE CANCER	0/303 (0%)		1/306 (0.3%)
UTERINE LEIOMYOMA	0/303 (0%)		1/306 (0.3%)
Nervous system disorders
CEREBROVASCULAR ACCIDENT	1/303 (0.3%)		0/306 (0%)
CHOREA	0/303 (0%)		1/306 (0.3%)
CONVULSION	0/303 (0%)		2/306 (0.7%)
HAEMORRHAGE INTRACRANIAL	0/303 (0%)		1/306 (0.3%)
LOSS OF CONSCIOUSNESS	0/303 (0%)		2/306 (0.7%)
PARKINSONISM	1/303 (0.3%)		0/306 (0%)
SYNCOPE	3/303 (1%)		2/306 (0.7%)
TOXIC ENCEPHALOPATHY	0/303 (0%)		1/306 (0.3%)
TRANSIENT ISCHAEMIC ATTACK	0/303 (0%)		1/306 (0.3%)
Psychiatric disorders
ABNORMAL BEHAVIOUR	1/303 (0.3%)		0/306 (0%)
AGGRESSION	2/303 (0.7%)		2/306 (0.7%)
AGITATION	1/303 (0.3%)		1/306 (0.3%)
ANXIETY	1/303 (0.3%)		1/306 (0.3%)
COMPLETED SUICIDE	4/303 (1.3%)		1/306 (0.3%)
CONFUSIONAL STATE	0/303 (0%)		1/306 (0.3%)
DELIRIUM	1/303 (0.3%)		0/306 (0%)
DELUSION	1/303 (0.3%)		2/306 (0.7%)
DEPRESSION	2/303 (0.7%)		6/306 (2%)
HALLUCINATION, AUDITORY	1/303 (0.3%)		1/306 (0.3%)
MAJOR DEPRESSION	2/303 (0.7%)		0/306 (0%)
PANIC ATTACK	1/303 (0.3%)		0/306 (0%)
PARANOIA	1/303 (0.3%)		0/306 (0%)
PSYCHOTIC BEHAVIOUR	1/303 (0.3%)		0/306 (0%)
PSYCHOTIC DISORDER	2/303 (0.7%)		1/306 (0.3%)
SUICIDAL BEHAVIOUR	1/303 (0.3%)		1/306 (0.3%)
SUICIDAL IDEATION	3/303 (1%)		7/306 (2.3%)
SUICIDE ATTEMPT	10/303 (3.3%)		8/306 (2.6%)
Renal and urinary disorders
NEPHROLITHIASIS	0/303 (0%)		1/306 (0.3%)
RENAL FAILURE	0/303 (0%)		2/306 (0.7%)
Reproductive system and breast disorders
UTERINE PROLAPSE	1/303 (0.3%)		0/306 (0%)
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE	1/303 (0.3%)		0/306 (0%)
ASPIRATION	0/303 (0%)		1/306 (0.3%)
ASTHMA	1/303 (0.3%)		1/306 (0.3%)
BRONCHIECTASIS	0/303 (0%)		1/306 (0.3%)
COUGH	1/303 (0.3%)		0/306 (0%)
PNEUMONIA ASPIRATION	1/303 (0.3%)		0/306 (0%)
UPPER AIRWAY OBSTRUCTION	0/303 (0%)		1/306 (0.3%)
Surgical and medical procedures
CORONARY ARTERY BYPASS	1/303 (0.3%)		0/306 (0%)
DEEP BRAIN STIMULATION	0/303 (0%)		1/306 (0.3%)
HAEMORRHOID OPERATION	1/303 (0.3%)		0/306 (0%)
HERNIA REPAIR	0/303 (0%)		1/306 (0.3%)
HIP ARTHROPLASTY	1/303 (0.3%)		0/306 (0%)
HYSTERECTOMY	0/303 (0%)		1/306 (0.3%)
KNEE ARTHROPLASTY	0/303 (0%)		1/306 (0.3%)
SHOULDER ARTHROPLASTY	1/303 (0.3%)		0/306 (0%)
SPINAL LAMINECTOMY	1/303 (0.3%)		0/306 (0%)
SURGERY	1/303 (0.3%)		0/306 (0%)
THYROIDECTOMY	0/303 (0%)		1/306 (0.3%)
Vascular disorders
HYPOTENSION	2/303 (0.7%)		0/306 (0%)
ILIAC ARTERY OCCLUSION	1/303 (0.3%)		0/306 (0%)
Other (Not Including Serious) Adverse Events
	A - Coenzyme Q10 2400 mg/Day		B - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	276/303 (91.1%)		280/306 (91.5%)
Gastrointestinal disorders
CONSTIPATION	26/303 (8.6%)		22/306 (7.2%)
DIARRHOEA	36/303 (11.9%)		43/306 (14.1%)
DYSPHAGIA	25/303 (8.3%)		21/306 (6.9%)
NAUSEA	31/303 (10.2%)		24/306 (7.8%)
VOMITING	25/303 (8.3%)		23/306 (7.5%)
General disorders
FATIGUE	19/303 (6.3%)		16/306 (5.2%)
Infections and infestations
BRONCHITIS	16/303 (5.3%)		19/306 (6.2%)
INFLUENZA	21/303 (6.9%)		17/306 (5.6%)
NASOPHARYNGITIS	27/303 (8.9%)		34/306 (11.1%)
SINUSITIS	14/303 (4.6%)		19/306 (6.2%)
UPPER RESPIRATORY TRACT INFECTION	23/303 (7.6%)		27/306 (8.8%)
URINARY TRACT INFECTION	33/303 (10.9%)		46/306 (15%)
Injury, poisoning and procedural complications
CONTUSION	10/303 (3.3%)		21/306 (6.9%)
FALL	72/303 (23.8%)		84/306 (27.5%)
LACERATION	14/303 (4.6%)		23/306 (7.5%)
Investigations
WEIGHT DECREASED	25/303 (8.3%)		33/306 (10.8%)
Nervous system disorders
BALANCE DISORDER	19/303 (6.3%)		21/306 (6.9%)
CHOREA	37/303 (12.2%)		44/306 (14.4%)
DIZZINESS	15/303 (5%)		16/306 (5.2%)
HEADACHE	17/303 (5.6%)		14/306 (4.6%)
Psychiatric disorders
ANXIETY	36/303 (11.9%)		42/306 (13.7%)
DEPRESSION	61/303 (20.1%)		66/306 (21.6%)
INSOMNIA	35/303 (11.6%)		64/306 (20.9%)
IRRITABILITY	36/303 (11.9%)		38/306 (12.4%)
Respiratory, thoracic and mediastinal disorders
COUGH	13/303 (4.3%)		19/306 (6.2%)

Limitations/Caveats

An interim analysis for futility revealed a conditional power of < 5% for the primary analysis, and the trial was halted in July, 2014. Only data collected prior to this time were included in the final analyses.

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Certain Agreements

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

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