UMIN-CTR Clinical Trial

Public title

A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Safety and Pharmacokinetic Study of MSA-01 (reduced form of CoQ₁₀) in Healthy Adult Males

Acronym

A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Safety and Pharmacokinetic Study of MSA-01 (reduced form of CoQ₁₀) in Healthy Adult Males

Scientific Title

A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Safety and Pharmacokinetic Study of MSA-01 (reduced form of CoQ₁₀) in Healthy Adult Males

Scientific Title:Acronym

A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Safety and Pharmacokinetic Study of MSA-01 (reduced form of CoQ₁₀) in Healthy Adult Males

Region

Japan

Condition

Multiple system atrophy

Classification by specialty

Neurology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate the safety and pharmacokinetics of MSA-01 in healthy adult males using high dose

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Explanatory

Developmental phase

Phase I

Primary outcomes

1)plasma concentration and pharmacokinetic parameters of MSA-01: C_max, AUC_0-t, AUC_0-inf(if applicable), t_max, t_1/2, Lamda-z, CL/F, Vz/F and MRT(if applicable)
2)safety: clinical examination, vital signs, body weight, laboratory tests, 12-lead ECG, the relationship between drug concentration and QT/QTc interval, and adverse events

Key secondary outcomes

1)plasma concentration of ubiquinone
2)drug concentration of MSA-01 and ubiquinone in leucocytes and cerebrospinal fluid

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

<MSA-01 group>
To receive MSA-01, 900, 1200 and 1500mg once a day from Day 1 to Day 14 daily

Interventions/Control_2

<placebo group>
To receive placebo once a day from Day 1 to Day 14 daily

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

35

years-old

>=

Gender

Male

Key inclusion criteria

Participants may be included in the study only if they meet all of the following criteria:
1. are Japanese healthy adult males between the age of 20 and 35.
Healthy adult are defined as adults who have no disorders requiring treatment as a result of medical history, clinical examination, laboratory test, vital signs (blood pressure in sitting position, pulse rate and armpit temperature), 12-lead ECG, blood test for infection, and urinary drug screening
2. have a body mass index of over 18.5 kg/m² on screening visit, under 25.0 kg/m²(approximate body weight over 50.0kg)
3. non-smoker or men who have not smoked for over half a year
4. are capable of visiting the all visit and completing the study
5. have given written informed consent and follow study procedures

Key exclusion criteria

Participants will be excluded from the study if they meet any of the following criteria:
1. are persons who have previously received ubiquinone or ubiquinol
2. family history of multiple system atrophy
3. are persons who have clinically significant disease and are not considered healthy by the investigator as a result of clinical examination, vital signs (blood pressure in sitting position, pulse rate and armpit temperature), 12-lead ECG and clinical examination on screening visit or are not suitable for participation judging from medical history
4. have a significant hepatic disease
5. history or presence of gastrointestinal, hepatic or renal disease known to affect absorption, distribution, metabolism and excretion
6. show positive findings on urinary drug screening on screening visit
7. are concurrently plan to be enrolled in other clinical trial or PMS study
8. are persons who are enrolled in other clinical trial of PMS study and have previously received the investigational product in this study within 3 months from the first administration of investigational product
9. history of drug or another allergy or have an idiosyncrasy (except persons with no evidence of hay fever)
10. history of drug or alcohol dependence
11. have an average weekly alcohol intake that exceeds 14 units per week (1 unit = 150 mL of wine; 350 mL of beer; 45 mL of 80-proof distilled spirits)
12. regularly use prescription medication or over-the-counter medication such as vitamins, crude drug, herbal preparations or supplement and are unable to stop within 14 days prior to administration of investigational product
13. are not willing to or unable to follow study procedures
14. are withdrawn over 400 mL within 4 months or withdrawn over 200 mL within a months from the first administration of investigational product
15. are considered inadequate to perform a lumbar puncture by the investigator
16. are considered inadequate to participate in the study by the investigator

Target sample size

24

Name of lead principal investigator

1st name
Middle name
Last name	Shoji Tsuji

Organization

The University of Tokyo Hospital

Division name

Department of Neurology

Zip code

Address

7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

TEL

03-3815-5411

Email

tsuji@m.u-tokyo.ac.jp

Name of contact person

1st name
Middle name
Last name	Toshio Ga

Organization

The University of Tokyo Hospital

Division name

Unit for Early and Exploratory Clinical Development

Zip code

Address

7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

TEL

03-5800-9083

Homepage URL

Email

tga-tky@umin.org

Institute

Department of Neurology, The University of Tokyo Hospital

Institute

Department

Personal name

Organization

AMED

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

東京大学医学部附属病院(東京都)
The University of Tokyo Hospital(Tokyo)

Date of disclosure of the study information

2015

Year

03

Month

03

Day

URL releasing protocol

https://onlinelibrary.wiley.com/doi/full/10.1111/ncn3.12566

Publication of results

Published

URL related to results and publications

https://onlinelibrary.wiley.com/doi/full/10.1111/ncn3.12566

Number of participants that the trial has enrolled

32

Results

Thirty-two participants provided informed consent to participate in this study. No clinically relevant changes in standard laboratory tests, physical examination, vital signs, or electrocardiogram attributable to ubiquinol administration were observed in any groups. The trough of plasma ubiquinol levels after repeated administration for 14 days reached a steady state, and the plasma ubiquinol levels in the 1500 mg/day-administered group tended to be the highest.

Results date posted

2022

Year

01

Month

18

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2021

Year

12

Month

03

Day

Baseline Characteristics

All 32 subjects were male, with an average age of 28.3 years (22-35 years), an average height of 171.04 cm (163.6-180.6 cm), and an average weight of 63.54 kg (52.4-77.5 kg). The average BMI was 21.70 kg / m2 (18.8 to 24.9 kg / m2). Eight patients (25.0%) had a medical history and complications, but none of the subjects were concomitant with the drug, and all patients had a negative urinary drug test.

Participant flow

The trial consisted of a screening period (up to 14 days), a pre-observation period (2 days), a repeated-dose period (14 days), and a follow-up period (14 days). At the time of the screening visit, written informed consent was obtained before any tests were performed.

Adverse events

Adverse events were observed in two of the eight participants (25.0%) in the placebo group, seven of the twelve participants (58.3%) in the 900 mg group, two of the six participants (33.3%) in the 1200 mg group, and six of the six participants (100.0%) in the 1500 mg group. The adverse events for which a causal relationship with the study drug could not be ruled out were APTT prolongation (two in the 900 mg group), lymphadenopathy (one in the 1200 mg group), and cheilitis and oropharyngeal discomfort (both in the 1500 mg group). Of these, the two participants (two in the 900 mg group) with APTT prolongation discontinued the study .
All adverse events were mild in severity, and no moderate or severe events were reported. No serious adverse events occurred.

Outcome measures

The primary endpoints were safety, plasma levels of ubiquinol and pharmacokinetic parameters including maximum concentration (Cmax), area under the plasma concentration-time curve up to a certain point (AUC0-t), area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf), time of maximum concentration (Tmax), time of elimination half-life (t1/2), terminal-phase elimination rate constant (lambda z), apparent oral clearance (CL/F), apparent volume of distribution (Vz/F), and mean residence time (MRT). Safety was assessed by on the basis of subjective symptoms obtained by interview and other findings by physical examination, vital signs, body weight, laboratory tests, 12-lead electrocardiogram (ECG) including the QT/QTc interval, and any adverse events.
The secondary endpoints included levels of ubiquinone in plasma and levels of total coenzyme Q10 (sum of ubiquinol and ubiquinone levels) in peripheral blood mononuclear cells and cerebrospinal fluid.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2015

Year

01

Month

29

Day

Date of IRB

Anticipated trial start date

2015

Year

07

Month

27

Day

Last follow-up date

2015

Year

11

Month

27

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2015

Year

03

Month

03

Day

Last modified on

2022

Year

01

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019376