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Trial registered on ANZCTR


Registration number
ACTRN12611000228987
Ethics application status
Approved
Date submitted
9/02/2011
Date registered
3/03/2011
Date last updated
21/07/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Assess the Safety, Tolerability and Effects of Compound Edaravone Injection (Edaravone + Borneol).
Scientific title
A Randomized, Single-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Edaravone + (+)-Borneol When Administered Intravenously in Healthy Subjects
Secondary ID [1] 253582 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
This study involves recruiting healthy subjects to trial a drug intended to treat Ischaemic Stroke. 261138 0
Condition category
Condition code
Stroke 259291 259291 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Single Ascending Dose study. Each subject only receives one dose level once during the study. The cohort is completed and reviewed by a safety review panel before dosing for the next cohort commences. There are 6 cohorts comprised of 8 subjects. The study drug is administered via intravenous injection over 30 minutes and the dosing regieme for each cohort is listed below:

Cohort 1: 5 mg Edaravone + 1.25 mg Borneol compound or placebo
Cohort 2: 15 mg Edaravone + 3.75 mg Borneol compound or placebo
Cohort 3: 30 mg Edaravone + 7.5 mg Borneol compound or placebo
Cohort 4: 60 mg Edaravone + 15 mg Borneol compound or placebo
Cohort 5: 90 mg Edaravone + 22.5 mg Borneol compound or placebo
Cohort 6: 120 mg Edaravone + 30 mg Borneol compound or placebo
Intervention code [1] 257980 0
Treatment: Drugs
Comparator / control treatment
Normal Saline
Control group
Placebo

Outcomes
Primary outcome [1] 262103 0
The primary objective is to evaluate the safety and tolerability of rising single doses of the combination of Compound Edaravone when administered intravenously in healthy male and female adult subjects.

Safety will be assessed by measuring: vital signs (blood pressure, pulse rate, temperature, and oxygen saturation), ECG (heart tracing), safety blood tests, physical examination findings, and adverse events. Vital signs and adverse events will be assessed daily at each visit. ECG readings will be assessed at screening, Day -1, Day 1, Day 2, and Day 3. Blood tests will be assessed at screening, Day -1, Day 2, Day 3, and at follow-up. Brief physical examinations will be done on Day -1 and a standard physical examination will be done at screening and at the final follow-up visit. A total of 91.5 mL of blood will be collected from each subject for analysis of safety laboratory parameters.
Timepoint [1] 262103 0
Safety and tolerability will be assessed by a Safety Review Panel at last patient, last visit for each cohort. The final visit for each participant will occur on Day 8.

The adverse effects associated with (+)-borneol reported in herbal medicines containing (+)-borneol include nausea, vomiting, confusion, dizziness and cramps. Conditions which have been reported with the use of Edaravone in up to 5% of cases are: Rash, redness, swelling, rashes, itching, Injection site rash, injection site swelling and redness, Fever, sensation of heat, increased blood pressure and changes in blood test results.
Secondary outcome [1] 273158 0
The secondary objective is to characterize the single-dose pharmacokinetics (PK) of Edaravone and Borneol in healthy male and female adult subjects.
Timepoint [1] 273158 0
In all cohorts, blood samples for PK analysis will be collected pre-dose and at 5, 15, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 26, and 48 hours after the start of infusion.

Eligibility
Key inclusion criteria
1. Healthy adult male and female subjects, 18-55 years of age, inclusive, at the time of signing the informed consent;

2. Body weight greater than or equal to 50 kg and body mass index (BMI) within the range 18-30 kg/m2, inclusive, at screening;

3. Medically healthy subjects with clinically insignificant screening and check-in results (medical histories, 12-lead ECG, physical exam, and laboratory tests);

4. Women of childbearing potential with a negative urine pregnancy test at screening and check-in who are not breastfeeding, do not plan to become pregnant during the study, and agree to use an approved method of birth control during the study;

5. Male subjects must agree to use barrier contraception (condom with spermicide) in addition to having their female partner (if of child-bearing potential) use another acceptable form of contraception (IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, or subdermal hormonal implant) from first dose until 30 days following the last administration of study drug;

6. Female subjects, if of child-bearing potential, must agree to use an acceptable form of contraception (IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, or subdermal hormonal implant) in addition to having their male partner use barrier contraception (condom with spermicide) from first dose until 30 days following the last administration of study drug. Female subjects who are NOT of child-bearing potential include those who have a history of tubal ligation, hysterectomy, or bilateral salpingooopherectomy, or who have had no menstrual period for >12 months, confirmed by a screening follicle stimulating hormone (FSH) level in the postmenopausal range;

7. Hemoglobin level within normal limits (WNL) of the reference laboratory (one repeat is allowed for a hemoglobin level that falls within 0.3 g/dL of the upper or lower limit of the reference range); and

8. Subjects who are able to understand and to give their signed informed consent before any trial related procedures are performed.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Subjects with, or a history of, cancer (not including basal cell skin cancer greater than 5 years prior), diabetes or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, hematological, dermatological, neurological, psychiatric or other major
disorder;

2. Presence or history of hepatic or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of medicines;

3. Systolic blood pressure (SBP) outside the range of 90 to 140 mmHg, diastolic blood pressure (DBP) outside the range of 40 to 90 mmHg, and/or pulse rate outside the range of 40 to 100 bpm at screening or check-in. One repeat blood pressure measurement may be performed if SBP is between 141 and 150 mmHg or DBP is between 91 and 95;

4. Clinically significant abnormality on ECG in the judgment of the Investigator;

5. Microscopic hematuria defined as >5 red blood cells (RBC) per high powered field (HPF) in a male or a non-menstruating female; 1 repeat allowed within several days of screening, including (but not limited to) females who are menstruating at the time of screening;

6. Reticulocyte value (percent reticulocytes) of more than 1% above the upper limit of normal (ULN) for the reference laboratory;

7. Urine protein > trace on a standard dip stick test (1 repeat allowed);

8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times the ULN;

9. Oxygen saturation by pulse oximetry <95%;

10. History of clinically significant drug and/or food allergies as determined by the Principal Investigator (PI);

11. History of clinically significant cardiac arrhythmia;

12. Subject is not willing to abstain from alcohol for 48 hours prior to the start of the first dose until completion of the post-study follow-up assessments;

13. Average weekly alcohol intake of greater than 21 units or an average daily intake of greater than 3 units (One unit is equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine.);

14. Recent history (within 2 years) or currently diagnosed alcohol or drug abuse, in the judgement of the Investigator;

15. Tobacco or nicotine replacement product use within the 6 months prior to first dose through the follow-up visit, or a positive urine screen for cotinine;

16. Hypersensitivity or idiosyncratic reaction to compounds related to the study drug;

17. Use of substances known to be strong inhibitors or inducers of cytochrome P450 enzymes within 14 days prior to the first dose;

18. Use of prescription or non-prescription drugs including vitamins, herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication;

19. Consumption of food or beverage containing grapefruit or cranberry within 7 days prior to the first dose of study medication;

20. Donation of whole blood in excess of 500 mL within 30 days prior to check-in;

21. Plasma donation within 7 days prior to check-in;

22. Subject participated in an investigational clinical study within 30 days (of last dose of previous study drug) prior to the first dosing, or within days calculated as 10 times the half-life of the compound that the subject was treated with, whichever is longer or participated in the early cohorts of the current study. Factors other than the half-life of the compound, such as accumulation of tissue, muscle or organ, should also be considered for the enrollment;

23. Positive test for HIV antibody, hepatitis B surface antigen, hepatitis C antibody, or hepatitis C surface antigen at screening;

24. Positive urine screen for drugs of abuse at screening or check-in; or

25. Any condition that, in the opinion of the Principal Investigator, would complicate or compromise the study, or the well-being of the subject.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 258469 0
Commercial sector/Industry
Name [1] 258469 0
Jiangsu Simcere Pharmaceutical Research Co., Ltd
Address [1] 258469 0
699-18 Xuan Wu Avenue
Xuan Wu District, Nanjing
Jiangsu Province 210042,
People's Republic of China
Country [1] 258469 0
China
Primary sponsor type
Commercial sector/Industry
Name
Medpace Australia Pty Limited
Address
Omnico Business Centre
Suite 1, Building 26
270 Ferntree Gully Rd.
NOTTING HILL, VIC. 3168
Country
Australia
Secondary sponsor category [1] 257616 0
None
Name [1] 257616 0
Address [1] 257616 0
Country [1] 257616 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260449 0
Bellberry Limited
Ethics committee address [1] 260449 0
229 Greenhill Road
Dulwich
South Australia 5065
Ethics committee country [1] 260449 0
Australia
Date submitted for ethics approval [1] 260449 0
02/02/2011
Approval date [1] 260449 0
Ethics approval number [1] 260449 0

Summary
Brief summary
Cerebrovascular disease is a disease of the blood vessels supplying the brain. Cerebrovascular disease poses a serious threat and is one of the three leading causes of death in humans. Cerebral stroke (a blockage, or bleed in the brain) leads to a lack of oxygen to the brain. Although there are many drugs used to treat this lack of oxygen resulting from cerebral stroke, these drugs do not work well enough. There is a need for a drug that can treat the injury, which is a result of a lack of oxygen, from cerebrovacsular disease.

Edaravone is a drug that can be used to improve the neurological symptoms and dysfunction in daily life caused by a lack of oxygen to the brain tissue from a cerebral stroke. Although Edaravone is currently known to help people who have had a cerebral stroke, the development of a better drug is still needed.

Compound Edaravone Injection (study drug) is a combination of Edaravone and a second medication, (+)-borneol. It is believed the combination of these two drugs in specific amounts can further improve the recovery of patients who experience a cerebral stroke. Both Edaravone and (+)-borneol have been used in humans, but not in combination with each other as a single compound.

The main purpose of this study is to evaluate the safety and tolerability of single doses of Compound Edaravone Injection (study drug) administered to healthy male and female adults. A second objective is to look at the pharmacokinetics (the study of how much study drug is in your blood at different time periods) of each dose of Compound Edaravone Injection (study drug) in healthy male and female adults.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32169 0
Address 32169 0
Country 32169 0
Phone 32169 0
Fax 32169 0
Email 32169 0
Contact person for public queries
Name 15416 0
Michael Tonso
Address 15416 0
Omnico Business Centre
Suite 1, Building 26
270 Ferntree Gully Rd.
NOTTING HILL, VIC. 3168
Country 15416 0
Australia
Phone 15416 0
+61 (0)3 9541 2100
Fax 15416 0
Email 15416 0
m.tonso@medpace.com
Contact person for scientific queries
Name 6344 0
Michael Tonso
Address 6344 0
Omnico Business Centre
Suite 1, Building 26
270 Ferntree Gully Rd.
NOTTING HILL, VIC. 3168
Country 6344 0
Australia
Phone 6344 0
+61 (0)3 9541 2100
Fax 6344 0
Email 6344 0
m.tonso@medpace.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary