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A Study of TTYP01 in Healthy Adult Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04370431
Recruitment Status : Recruiting
First Posted : May 1, 2020
Last Update Posted : July 10, 2020
Sponsor:
Collaborators:
TIGERMED AUSTRALIA PTY LIMITED
CMAX Clinical Research Pty Ltd
Information provided by (Responsible Party):
Auzone Biological Technology Pty Ltd

Brief Summary:

This is integrated Phase 1, Single centre, Randomized study will be conducted in 3 parts, each with a specific primary objective:

Part A: To characterise the safety and tolerability of TTYP01 in healthy adult subjects; Part B: To evaluate the bioavailability of TTYP01 tablets in healthy adult subjects; Part C: To characterise the food effect of TTYP01 tablets in healthy adult subjects under the fasted or fed condition.

The secondary objectives of the study are to evaluate the pharmacokinetic (PK) profiles of TTYP01 tablets in healthy adult subjects, and the effects of gender on the PK of TTYP01 tablets in healthy adults. In Part A of the study, a total of 32 healthy adult subjects will be enrolled over four consecutive cohorts (8 per cohort), with participants receiving a single dose of TTYP01 at one of four levels (60, 120, 10 or 240 mg), to assess the PK and safety of TTYP01. In Part B, 16 healthy adults will be randomized into 2 groups, and the comparison of the PK of edaravone (TTYP01 and intravenous (IV) edaravone) will be evaluated using a randomized, open-label, four-period crossover design under fasted conditions. In the first crossover period, subjects will receive a single fixed dose of TTYP01 followed by the alternate IV dose after completion of the washout phase, and in the second crossover period, subjects will receive a higher fixed dose of TTYP01 followed by the alternate IV dose after completion of the washout phase. In Part C, 12 healthy subjects will be enrolled to evaluate the effect of food on the PK of TTYP01 using a randomized, open-label, two-period cross-over design. Participants will be randomized into two groups and administered a fixed dose of TTYP01 on Day 1 (Period 1) under the fed conditions and the second dosing day (Period 2) under the fasted conditions, while the other group being administered a fixed dose of TTYP01 on Day 1 (Period 1) under the fasted conditions and the second dosing day (Period 2) under the fed conditions.


Condition or disease Intervention/treatment Phase
Healthy Adult Subjects Drug: TTYP01 single ascending doses Drug: Placebo Drug: TTYP01, 60 mg Drug: TTYP01, 120 mg Drug: Radicut® (ampoule), 30 mg Drug: Radicut® (bag) , 60 mg Drug: TTYP01, up to 120 mg Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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.
Actual Study Start Date : April 24, 2020
Estimated Primary Completion Date : March 4, 2021
Estimated Study Completion Date : August 4, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Edaravone

Arm Intervention/treatment
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.
Drug: 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)
Other Name: edaravone tablet

Placebo Comparator: Part A: Placebo
Placebo control for Part A of the study
Drug: 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.
Drug: TTYP01, 60 mg
TTYP01 oral tablets (30 mg edaravone per tablet)
Other Name: Edaravone tablet

Drug: TTYP01, 120 mg
TTYP01 oral tablets (30 mg edaravone per tablet)
Other Name: Edaravone tablet

Drug: 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
Other Name: Edaravone injection

Drug: 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
Other Name: Edaravone injection

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.
Drug: TTYP01, 60 mg
TTYP01 oral tablets (30 mg edaravone per tablet)
Other Name: Edaravone tablet

Drug: TTYP01, 120 mg
TTYP01 oral tablets (30 mg edaravone per tablet)
Other Name: Edaravone tablet

Drug: 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
Other Name: Edaravone injection

Drug: 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
Other Name: Edaravone injection

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.
Drug: 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)
Other Name: Edaravone tablet

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.
Drug: 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)
Other Name: Edaravone tablet




Primary Outcome Measures :
  1. Adverse events [ Time Frame: until the last follow-up visit, up to 4 weeks ]
    Frequencies (number and percentage) of subjects with one or more AEs

  2. change in hemoglobin (g/L) [ Time Frame: up to 6 days post each dose ]
    measured by hematology test

  3. change in hematocrit (ratio) [ Time Frame: up to 6 days post each dose ]
    measured by hematology test

  4. change in red blood cell count (cells x 10^12/L) [ Time Frame: up to 6 days post each dose ]
    measured by hematology test

  5. change in white blood cell (WBC) count (cells x 10^9/L) [ Time Frame: up to 6 days post each dose ]
    measured by hematology test

  6. change in platelet count (cells x 10^9/L) [ Time Frame: up to 6 days post each dose ]
    measured by hematology test

  7. change in total neutrophils count (cells x 10^9/L) [ Time Frame: up to 6 days post each dose ]
    measured by hematology test

  8. change in lymphocytes count (cells x 10^9/L) [ Time Frame: up to 6 days post each dose ]
    measured by hematology test

  9. change in monocytes count (cells x 10^9/L) [ Time Frame: up to 6 days post each dose ]
    measured by hematology test

  10. change in eosinophils count (cells x 10^9/L) [ Time Frame: up to 6 days post each dose ]
    measured by hematology test

  11. change in basophils count (cells x 10^9/L) [ Time Frame: up to 6 days post each dose ]
    measured by hematology test

  12. change in serum sodium (mmol/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  13. change in serum potassium (mmol/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  14. change in serum chloride (mmol/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  15. change in serum calcium (mmol/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  16. change in serum glucose (mmol/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  17. change in serum urea (mmol/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  18. change in serum creatinine (umol/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  19. change in serum total bilirubin (umol/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  20. change in aspartate aminotransferase (AST) (U/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  21. change in alanine aminotransferase (ALT) (U/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  22. change in alkaline phosphatase (ALP) (U/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  23. change in serum creatine kinase (CK) (U/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  24. change in serum albumin (g/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  25. change in serum phosphate (mmol/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  26. change in serum lipase (U/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  27. change in serum total protein (g/L) [ Time Frame: up to 6 days post each dose ]
    measured by serum chemistry

  28. change in urine pH [ Time Frame: up to 6 days post each dose ]
    measured by urinalysis

  29. change in urine specific gravity [ Time Frame: up to 6 days post each dose ]
    measured by urinalysis

  30. change in urine glucose [ Time Frame: up to 6 days post each dose ]
    measured by urinalysis

  31. change in urine protein [ Time Frame: up to 6 days post each dose ]
    measured by urinalysis

  32. change in urine ketones [ Time Frame: up to 6 days post each dose ]
    measured by urinalysis

  33. change in urine blood [ Time Frame: up to 6 days post each dose ]
    measured by urinalysis

  34. change in urine casts [ Time Frame: up to 6 days post each dose ]
    measured by microscopic analysis, if any abnormalities in urinalysis are detected

  35. change in urine crystals [ Time Frame: up to 6 days post each dose ]
    measured by microscopic analysis, if any abnormalities in urinalysis are detected

  36. change in urine epithelial cells [ Time Frame: up to 6 days post each dose ]
    measured by microscopic analysis, if any abnormalities in urinalysis are detected

  37. change in urine bacteria (cfu/L) [ Time Frame: up to 6 days post each dose ]
    measured by microscopic analysis, if any abnormalities in urinalysis are detected

  38. change in urine red blood cells (Cells x 10^9/L) [ Time Frame: up to 6 days post each dose ]
    measured by microscopic analysis, if any abnormalities in urinalysis are detected

  39. change in urine white blood cells (Cells x 10^9/L) [ Time Frame: up to 6 days post each dose ]
    measured by microscopic analysis, if any abnormalities in urinalysis are detected

  40. change in systolic blood pressure (mmHg) [ Time Frame: up to 6 days post each dose ]
  41. change in diastolic blood pressure (mmHg) [ Time Frame: up to 6 days post each dose ]
  42. change in pulse rate (bpm) [ Time Frame: up to 6 days post each dose ]
  43. change in body temperature (celsius) [ Time Frame: up to 6 days post each dose ]
  44. Change in QT intervals (msec) [ Time Frame: up to 6 days post each dose ]
    Measured using a 12 Lead Electrocardiogram

  45. Change in RR intervals (msec) [ Time Frame: up to 6 days post each dose ]
    Measured using a 12 Lead Electrocardiogram

  46. Change in PR intervals (msec) [ Time Frame: up to 6 days post each dose ]
    Measured using a 12 Lead Electrocardiogram

  47. Change in QRS duration (msec) [ Time Frame: up to 6 days post each dose ]
    Measured using a 12 Lead Electrocardiogram

  48. Change in corrected QTcF (msec) [ Time Frame: up to 6 days post each dose ]
    Calculated using measurements by a 12 Lead Electrocardiogram

  49. clinically significant abnormality in brief physical examinations [ Time Frame: up to 6 days post each dose ]
    clinically significant abnormality in skin, lungs, cardiovascular system, and abdomen (spleen and liver)


Secondary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) [ Time Frame: up to 24 hours post each dose ]
  2. Time of maximum plasma concentration (Tmax) [ Time Frame: up to 24 hours post each dose ]
  3. Area under the plasma concentration-time curve from time-zero extrapolated to infinite time (AUC0-inf) [ Time Frame: up to 24 hours post each dose ]
  4. Area under the plasma concentration-time curve from time-zero to the time of the last measurable concentration (AUC0-last) [ Time Frame: up to 24 hours post each dose ]
  5. 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) [ Time Frame: up to 24 hours post each dose ]
  6. Apparent volume of distribution (Vd/F) [ Time Frame: up to 24 hours post each dose ]
  7. Terminal half-life(T1/2) [ Time Frame: up to 24 hours post each dose ]
  8. Apparent oral clearance (CL/F) [ Time Frame: up to 24 hours post each dose ]
  9. Mean retention time (MRT) [ Time Frame: up to 24 hours post each dose ]
  10. Lambda z - the reciprocal of elimination rate constant (λz) [ Time Frame: up to 24 hours post each dose ]
  11. Fabs-bioavailability value (Fabs) [ Time Frame: up to 24 hours post each dose ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04370431


Contacts
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Contact: Haifeng Ding, PhD +86 (512) 6843 1353 dinghf@szauzone.com
Contact: Lisa (Haixia) Zhan, Master haixia.zhan@tigermedgrp.com

Locations
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Australia, South Australia
CMAX Clinical Research Pty Ltd Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Briohny Johnston    +61 8 7088 7900    briohny.johnston@cmax.com.au   
Principal Investigator: Sepehr Shakib, MD         
Sponsors and Collaborators
Auzone Biological Technology Pty Ltd
TIGERMED AUSTRALIA PTY LIMITED
CMAX Clinical Research Pty Ltd
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Responsible Party: Auzone Biological Technology Pty Ltd
ClinicalTrials.gov Identifier: NCT04370431    
Other Study ID Numbers: Auzone-01
First Posted: May 1, 2020    Key Record Dates
Last Update Posted: July 10, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Edaravone
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs