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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04370431




Registration number
NCT04370431
Ethics application status
Date submitted
18/04/2020
Date registered
1/05/2020
Date last updated
2/04/2021

Titles & IDs
Public title
A Study of TTYP01 in Healthy Adult Subjects
Scientific title
A Phase I, Single Center, Randomized, Single-Ascending Dose, Pharmacokinetic and Safety Study (Part A), Bioavailability Comparison Study (Part B) and Food Effect Study (Part C) in Healthy Adult Subjects.
Secondary ID [1] 0 0
Auzone-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Adult Subjects 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TTYP01 single ascending doses
Treatment: Drugs - Placebo
Treatment: Drugs - TTYP01, 60 mg
Treatment: Drugs - TTYP01, 120 mg
Treatment: Drugs - Radicut® (ampoule), 30 mg
Treatment: Drugs - Radicut® (bag) , 60 mg
Treatment: Drugs - TTYP01, up to 120 mg

Experimental: PartA: TTYP01 single ascending doses - In Part A: a single-ascending-dose (SAD) escalation study with four consecutive cohorts, single ascending doses of TTYP01 (60, 120, 180 and 240 mg) will be orally administrated.

Placebo comparator: Part A: Placebo - Placebo control for Part A of the study

Experimental: Part B: TTYP01 (oral edaravone) first then IV edaravone - Randomized, Open-label, Four-period and Crossover design. A single dose of edaravone in each treatment period. Period 1: 60 mg oral edaravone tablet (TTYP01); Period 2: 30 mg IV edaravone (Radicut® ampoule), Period 3: 120 mg oral edaravone tablet (TTYP01); Period 4: 60 mg IV edaravone (Radicut® bag). Each dose will be spearated by a minimum of 7 days washout period.

Experimental: Part B: IV edaravone first then TTYP01 (oral edaravone) - Randomized, Open-label, Four-period and Crossover design. A single dose of edaravone in each treatment period. Period 1: 30 mg IV edaravone (Radicut® ampoule); Period 2: 60 mg oral edaravone tablet (TTYP01); Period 3: 60 mg IV edaravone (Radicut® bag); Period 4: 120 mg oral edaravone tablet (TTYP01). Each dose will be spearated by a minimum of 7 days washout period.

Experimental: Part C: TTYP01: fasted dosing first then fed dosing - Randomized, open-Label, Two-period and Crossover design. A fix oral dose of TTYP01 tablet in each treatment period. Period 1: under fasted condition; Period 2: under fed condition. Each dose will be spearated by a minimum of 7 days washout period.

Experimental: Part C: TTYP01: fed dosing first then fasted dosing - Randomized, open-Label, Two-period and Crossover design. A fix oral dose of TTYP01 tablet in each treatment period. Period 1: under fed condition; Period 2: under fasted condition. Each dose will be spearated by a minimum of 7 days washout period.


Treatment: Drugs: TTYP01 single ascending doses
TTYP01 (30 mg edaravone tablet) will be orally administrated at single ascending doses of 60 mg, 120 mg, 180 mg and 240 mg (n=6 per dose)

Treatment: Drugs: Placebo
Placebo control for Part A of the study

Treatment: Drugs: TTYP01, 60 mg
TTYP01 oral tablets (30 mg edaravone per tablet)

Treatment: Drugs: TTYP01, 120 mg
TTYP01 oral tablets (30 mg edaravone per tablet)

Treatment: Drugs: Radicut® (ampoule), 30 mg
An intravenous dose of edaravone injection, containing 30 mg edaravone in a 20 mL ampoule, will be administered at a dose of 30 mg over 30 minutes

Treatment: Drugs: Radicut® (bag) , 60 mg
An intravenous dose of edaravone injection, containing 30 mg edaravone in a 100 mL injection bag, will be administered at a dose of 60 mg over 60 minutes

Treatment: Drugs: TTYP01, up to 120 mg
TTYP01 oral tablets (30 mg edaravone per tablet). The fixed oral dose level of TTYP01 will depend on the results obtained in Part B of the study (no more than 120 mg)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse events
Timepoint [1] 0 0
until the last follow-up visit, up to 4 weeks
Primary outcome [2] 0 0
change in hemoglobin (g/L)
Timepoint [2] 0 0
up to 6 days post each dose
Primary outcome [3] 0 0
change in hematocrit (ratio)
Timepoint [3] 0 0
up to 6 days post each dose
Primary outcome [4] 0 0
change in red blood cell count (cells x 10^12/L)
Timepoint [4] 0 0
up to 6 days post each dose
Primary outcome [5] 0 0
change in white blood cell (WBC) count (cells x 10^9/L)
Timepoint [5] 0 0
up to 6 days post each dose
Primary outcome [6] 0 0
change in platelet count (cells x 10^9/L)
Timepoint [6] 0 0
up to 6 days post each dose
Primary outcome [7] 0 0
change in total neutrophils count (cells x 10^9/L)
Timepoint [7] 0 0
up to 6 days post each dose
Primary outcome [8] 0 0
change in lymphocytes count (cells x 10^9/L)
Timepoint [8] 0 0
up to 6 days post each dose
Primary outcome [9] 0 0
change in monocytes count (cells x 10^9/L)
Timepoint [9] 0 0
up to 6 days post each dose
Primary outcome [10] 0 0
change in eosinophils count (cells x 10^9/L)
Timepoint [10] 0 0
up to 6 days post each dose
Primary outcome [11] 0 0
change in basophils count (cells x 10^9/L)
Timepoint [11] 0 0
up to 6 days post each dose
Primary outcome [12] 0 0
change in serum sodium (mmol/L)
Timepoint [12] 0 0
up to 6 days post each dose
Primary outcome [13] 0 0
change in serum potassium (mmol/L)
Timepoint [13] 0 0
up to 6 days post each dose
Primary outcome [14] 0 0
change in serum chloride (mmol/L)
Timepoint [14] 0 0
up to 6 days post each dose
Primary outcome [15] 0 0
change in serum calcium (mmol/L)
Timepoint [15] 0 0
up to 6 days post each dose
Primary outcome [16] 0 0
change in serum glucose (mmol/L)
Timepoint [16] 0 0
up to 6 days post each dose
Primary outcome [17] 0 0
change in serum urea (mmol/L)
Timepoint [17] 0 0
up to 6 days post each dose
Primary outcome [18] 0 0
change in serum creatinine (umol/L)
Timepoint [18] 0 0
up to 6 days post each dose
Primary outcome [19] 0 0
change in serum total bilirubin (umol/L)
Timepoint [19] 0 0
up to 6 days post each dose
Primary outcome [20] 0 0
change in aspartate aminotransferase (AST) (U/L)
Timepoint [20] 0 0
up to 6 days post each dose
Primary outcome [21] 0 0
change in alanine aminotransferase (ALT) (U/L)
Timepoint [21] 0 0
up to 6 days post each dose
Primary outcome [22] 0 0
change in alkaline phosphatase (ALP) (U/L)
Timepoint [22] 0 0
up to 6 days post each dose
Primary outcome [23] 0 0
change in serum creatine kinase (CK) (U/L)
Timepoint [23] 0 0
up to 6 days post each dose
Primary outcome [24] 0 0
change in serum albumin (g/L)
Timepoint [24] 0 0
up to 6 days post each dose
Primary outcome [25] 0 0
change in serum phosphate (mmol/L)
Timepoint [25] 0 0
up to 6 days post each dose
Primary outcome [26] 0 0
change in serum lipase (U/L)
Timepoint [26] 0 0
up to 6 days post each dose
Primary outcome [27] 0 0
change in serum total protein (g/L)
Timepoint [27] 0 0
up to 6 days post each dose
Primary outcome [28] 0 0
change in urine pH
Timepoint [28] 0 0
up to 6 days post each dose
Primary outcome [29] 0 0
change in urine specific gravity
Timepoint [29] 0 0
up to 6 days post each dose
Primary outcome [30] 0 0
change in urine glucose
Timepoint [30] 0 0
up to 6 days post each dose
Primary outcome [31] 0 0
change in urine protein
Timepoint [31] 0 0
up to 6 days post each dose
Primary outcome [32] 0 0
change in urine ketones
Timepoint [32] 0 0
up to 6 days post each dose
Primary outcome [33] 0 0
change in urine blood
Timepoint [33] 0 0
up to 6 days post each dose
Primary outcome [34] 0 0
change in urine casts
Timepoint [34] 0 0
up to 6 days post each dose
Primary outcome [35] 0 0
change in urine crystals
Timepoint [35] 0 0
up to 6 days post each dose
Primary outcome [36] 0 0
change in urine epithelial cells
Timepoint [36] 0 0
up to 6 days post each dose
Primary outcome [37] 0 0
change in urine bacteria (cfu/L)
Timepoint [37] 0 0
up to 6 days post each dose
Primary outcome [38] 0 0
change in urine red blood cells (Cells x 10^9/L)
Timepoint [38] 0 0
up to 6 days post each dose
Primary outcome [39] 0 0
change in urine white blood cells (Cells x 10^9/L)
Timepoint [39] 0 0
up to 6 days post each dose
Primary outcome [40] 0 0
change in systolic blood pressure (mmHg)
Timepoint [40] 0 0
up to 6 days post each dose
Primary outcome [41] 0 0
change in diastolic blood pressure (mmHg)
Timepoint [41] 0 0
up to 6 days post each dose
Primary outcome [42] 0 0
change in pulse rate (bpm)
Timepoint [42] 0 0
up to 6 days post each dose
Primary outcome [43] 0 0
change in body temperature (celsius)
Timepoint [43] 0 0
up to 6 days post each dose
Primary outcome [44] 0 0
Change in QT intervals (msec)
Timepoint [44] 0 0
up to 6 days post each dose
Primary outcome [45] 0 0
Change in RR intervals (msec)
Timepoint [45] 0 0
up to 6 days post each dose
Primary outcome [46] 0 0
Change in PR intervals (msec)
Timepoint [46] 0 0
up to 6 days post each dose
Primary outcome [47] 0 0
Change in QRS duration (msec)
Timepoint [47] 0 0
up to 6 days post each dose
Primary outcome [48] 0 0
Change in corrected QTcF (msec)
Timepoint [48] 0 0
up to 6 days post each dose
Primary outcome [49] 0 0
clinically significant abnormality in brief physical examinations
Timepoint [49] 0 0
up to 6 days post each dose
Secondary outcome [1] 0 0
Maximum observed plasma concentration (Cmax)
Timepoint [1] 0 0
up to 24 hours post each dose
Secondary outcome [2] 0 0
Time of maximum plasma concentration (Tmax)
Timepoint [2] 0 0
up to 24 hours post each dose
Secondary outcome [3] 0 0
Area under the plasma concentration-time curve from time-zero extrapolated to infinite time (AUC0-inf)
Timepoint [3] 0 0
up to 24 hours post each dose
Secondary outcome [4] 0 0
Area under the plasma concentration-time curve from time-zero to the time of the last measurable concentration (AUC0-last)
Timepoint [4] 0 0
up to 24 hours post each dose
Secondary outcome [5] 0 0
The ratio of area under the plasma concentration-time curve from time-zero to the time of the last measurable concentration (AUC0-last) extrapolated to AUC0-inf over AUC0-inf (% AUCex)
Timepoint [5] 0 0
up to 24 hours post each dose
Secondary outcome [6] 0 0
Apparent volume of distribution (Vd/F)
Timepoint [6] 0 0
up to 24 hours post each dose
Secondary outcome [7] 0 0
Terminal half-life(T1/2)
Timepoint [7] 0 0
up to 24 hours post each dose
Secondary outcome [8] 0 0
Apparent oral clearance (CL/F)
Timepoint [8] 0 0
up to 24 hours post each dose
Secondary outcome [9] 0 0
Mean retention time (MRT)
Timepoint [9] 0 0
up to 24 hours post each dose
Secondary outcome [10] 0 0
Lambda z - the reciprocal of elimination rate constant (?z)
Timepoint [10] 0 0
up to 24 hours post each dose
Secondary outcome [11] 0 0
Fabs-bioavailability value (Fabs)
Timepoint [11] 0 0
up to 24 hours post each dose

Eligibility
Key inclusion criteria
* Age between 18 and 40, inclusive;
* Non-smokers, ex-smokers and moderate smokers will be included. "A moderate smoker is defined as someone smoking 5 cigarettes or less per day, an ex-smoker is someone who completely stopped smoking for at least 3 months.";
* If female, must be of non-childbearing potential (defined as either surgically sterilized or at least 1 year postmenopausal) or must agree to use a clinically acceptable method of contraception (e.g., oral, intrauterine device [IUD; diaphragm], injectable, transdermal or implantable contraception) or abstinence, for at least 1 month prior to randomization, during the study and 3 month following completion of the study. Females of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test at screening;
* Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive; and a total body weight >50 kg at screening for male subjects, total body weight > 45 kg for female subjects;
* Female subjects of child bearing potential and all male participants who have not had a vasectomy must use effective contraception during the study
* Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the subject prior to any study-specific procedures), and evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study;
* Willingness and ability to comply with study procedures and follow-up examination.
* Adequate organ function as evidenced by the following peripheral blood counts or serum chemistry values within 28 days before randomization:

1. Hemoglobin greater than or equal to 9 g/dL
2. Neutrophil count (ANC) greater than or equal to 1,500/microL
3. Platelet count greater than or equal to 100,000/microL
4. Serum creatinine less than or equal to 1.5 mg/dL (less than or equal to 132.6 micromol/L) and creatinine clearance greater than or equal to 60 ml/min
5. Creatine phosphokinase (CPK) less than or equal to 2x upper limit of normal (ULN)
6. Hepatic function variables:

1. Total bilirubin = 1.5x ULN
2. Total alkaline phosphatase (ALP) = 1.5x ULN, or if > 1.5x ULN, then ALP liver fraction or 5' nucleotidase must be =1x ULN
3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be = 2.5x ULN
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
* Subjects with a history of hypersensitivity to edaravone or any of the inactive ingredients of the formulation (such as sulfite and sodium bisulfite).
* Subjects with PR >240 msec, QRS =120 msec, or QTcF >450 msec for male & QTcF >470 msec for female on the screening or Day -1 ECG, or any clinically significant electrocardiographic abnormality in the opinion of the investigator.
* Male subjects with partners currently pregnant; male subjects able to father children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 3 months after the last dose of investigational product.
* Female subjects currently pregnant or lactating; female subjects able to bear children or of child bearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 3 months after the last dose of investigational product.
* Subjects whose urine drug/alcohol screening was positive at the time of screening and/or on Day-1.
* Subjects having difficulty in swallowing pills/tablets.
* Subjects smoking > 5 cigarettes per day within 3 months prior to the screening visit.
* Subjects unwilling or unable to comply with the Lifestyle Guidelines described in the protocol.
* Subjects who are investigational site staff members directly involved in the conduct of the studies and their family members, site staff members otherwise supervised by the Investigator, or subjects who are the sponsors' employees directly involved in the conduct of the studies.
* Evidence of any severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.
* Subjects who have participated in another clinical trial less than 3 months before or donated his/her blood in a quantity greater than 200 milliliters (mL) within 1 month of the screening period of this clinical trial.

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?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
SA
Recruitment hospital [1] 0 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Auzone Biological Technology Pty Ltd
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
TIGERMED AUSTRALIA PTY LIMITED
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
CMAX Clinical Research Pty Ltd
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sepehr Shakib, MD
Address 0 0
Royal Adelaide Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.