None listed
Conditions
Brief summary
Cyclo-Z treatment significantly improved insulin sensitivity in animal models of type 2 diabetes, further clinical trials of Cyclo-Z in diabetic subjects are warranted to determine if Cyclo-Z treatment results in clinical improvements. Since the completion of the pilot Phase 1 clinical trial and the Phase 2 obese Type 2 diabetes trial, the formulation of Cyclo-Z was changed from a capsule to a tablet form. The current study is intended to obtain the additional safety data and pharmacokinetics of escalating doses of the revised formulation of Cyclo-Z when dosed once and when dosed daily for 10 days in healthy volunteers.
Interventions
This is a Single Dose (Fed and Fasted State) and Multiple Dose Phase trial. Subjects will be randomised to either orally receive with Cyclo-Z or placebo at doses and intervals presented below.
Active treatment will be an oral tablet of Cyclo-Z, a combination of Cyclo (His-pro) (CHP) at doses between 6mg and 60mg and zinc.
In the Singe Ascending Dose (SAD) Phase, there will be up to 5 cohorts with 8 subjects (6 active and 2 placebo). A total of 40 subjects are planned if all 5 dose levels are c
This is a Single Dose (Fed and Fasted State) and Multiple Dose Phase trial. Subjects will be randomised to either orally receive with Cyclo-Z or placebo at doses and intervals presented below. Active treatment will be an oral tablet of Cyclo-Z, a combination of Cyclo (His-pro) (CHP) at doses between 6mg and 60mg and zinc. In the Singe Ascending Dose (SAD) Phase, there will be up to 5 cohorts with 8 subjects (6 active and 2 placebo). A total of 40 subjects are planned if all 5 dose levels are completed in the fasted state. The same 8 subjects (6 active, 2 placebo) from one dose cohort will be assessed for food effect after an approximately 7-day wash-out or 5 half-lives, whichever comes later. Cohort 1 will receive 6mg CHP plus 23mg zinc, administered by oral tablet. Cohort 2 will receive 15mg CHP plus 23 mg zinc, administered by oral tablet. Cohort 3 will receive 30mg CHP plus 46 mg zinc, administered by oral tablets. Cohort 4 will receive 45mg CHP plus 69 mg zinc, administered by oral tablets. Cohort 5 will receive 60mg CHP plus 92 mg zinc, administered by oral tablets. Dosing will take place in the morning on Day 1 under the supervision of the study staff. Subjects will each receive their first dose of study drug following a 12 hour fast. Water is allowed during the fast. Study drug compliance will be documented in the eCRF by recording: The date and time of the administration and the amount of tablets taken. Participants will not be allowed to participate in both the SAD and MAD cohorts, however one cohort from the SAD Fasted cohorts will be selected to complete the SAD Fed cohort. In the Multiple Ascending Dose (MAD) Phase, there will be up to 4 cohorts with 8 subjects (6 active and 2 placebo). A total of 32 subjects are planned if all 4 dose levels are completed. Cohort 1 will receive 6mg CHP plus 23mg zinc by oral tablet once daily for 10 days. Cohort 2 will receive 15mg CHP plus 23 mg zinc by oral tablet once daily for 10 days. Cohort 3 will receive 30mg CHP plus 46 mg zinc by oral tablets once daily for 10 days. Cohort 4 will receive 45mg CHP plus 69 mg zinc by oral tablets once daily for 10 days. Dosing will take place in the morning on dosing days under the supervision of the study staff. Subjects will each receive their first dose of study drug following a 12 hour fast. Water is allowed during the fast. Study drug compliance will be documented in the eCRF by recording: The date and time of the administration and the amount of tablets taken. Following the review of the SAD and MAD cohorts and dependent on the sponsor's review of trial data, the sponsor has allowed for the possibility to run an optional cohort(s). Should the sponsor and site proceed with the optional cohort(s), it will be assessing a Cyclo (his-pro) [CHP] only and/or a zonc only cohort with 8 subjects (6 active and 2 placebo). The dose for this optional cohort(s) will based on the emerging tolerability data from the MAD cohorts. New subjects will be recruited for this cohort. The optional cohort(s) will follow the same schedule as the MAD cohorts, receiving daily oral tablet(s) dosing for 10 days. Dosing will take place in the morning on dosing days under the supervision of the study staff. Subjects will each receive their first dose of study drug following a 12 hour fast. Water is allowed during the fast. Study drug compliance will be documented in the eCRF by recording: The date and time of the administration and the amount of tablets taken. An additional biocomparability cohort will be conducted as an open-label, two-way crossover evaluation to examine the PK and safety of two Cyclo-Z immediate release tablet formulations each containing 15mg CHP and 23mg zinc. This cohort will consist of a 4-week screening period and two periods (Period 1 and 2) that are separated by an outpatient washout time of 7 (plus or minus 3) days. Subjects will be consented and screened for enrollment up to 4 weeks prior to Day -1 (check-in) and those subjects who meet all of the inclusion criteria and none of the exclusion criteria at Screening and Day -1 will be eligible to participate. During each of the two periods, subjects will remain at the clinical site for a 72 hour inpatient period. Approximately 8 healthy subjects will be randomized on Day -1/1, in a 1:1 ratio, to receive 1 of 2 Cyclo-Z tablet formulations during Periods 1 and 2 (Tablet A/Tablet B or Tablet B/Tablet A).
Sponsors
NovMetaPharma Co., Ltd.
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
All subjects are required to meet the following criteria in order to be included in the study: 1. Male or female between 18 and 55 years of age. 2. Female subjects must be either: a. Surgically sterile (i.e., have had bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) at least 6 months before randomization, or b. Post-menopausal for at least 12 months prior to screening, or c. If of childbearing potential and sexually active, must agree to use a highly effective contraceptive method from screening to 30 days after the end of dosing. Females who are abstinent will not be required to use a contraceptive method unless they become sexually active. Females who are sexually active with partners of same gender will not be required to use a contraceptive method. 3. Sexually active male subjects with female partners of childbearing potential must use two reliable forms of contraception from screening to 30 days after the end of dosing. Note: The female partners of male subjects must agree to use double barrier method, which includes using highly reliable forms of contraception, and male partner must agree to use condom. Male subjects who are sexually active with partners of same gender must use a condom from screening to 30 days after end of dosing. Male subjects who are abstinent will not be required to use contraception unless they become sexually active. 4. Estimated creatinine clearance greater than 60 mL/min based on the Cockcroft-Gault calculation or serum creatinine value less then 1.5 times the upper limit of normal (ULN), unless deemed not clinically significant by the Investigator. 5. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values less than 1.5 times the upper limit of normal, unless deemed not clinically significant by the Investigator. 6. Be current non-smokers and also may not have used tobacco products (e.g., cigarettes, e-cigarettes, cigars, pipe tobacco) within the year prior to screening. 7. Good general health as determined by medical history, and by results of physical examination, vital signs, ECG, and clinical laboratory tests obtained within 14 days (2 weeks) prior to study drug administration. 8. Able to provide written informed consent and understand and comply with the requirements of the study.
Exclusion criteria
All subjects with the following characteristics will be excluded from the study: 1. Subject participation in more than one cohort. 2. History or presence of any clinically significant organ system disease that could interfere with the objectives of the study or the safety of the subjects. 3. Blood pressure and/or heart rate at outside the ranges 90-140 mmHg systolic, 40-90 mmHg diastolic, heart rate 40-100 beats/min. 4. 12-lead ECG with any abnormality judged by the Investigator to be clinically significant, QT >500 milliseconds (msec), or QTcF interval of greater than 450 msec for men or greater than 470 msec for women. 5. Presence or history of any abnormality or illness, which in the opinion of the Investigator may affect absorption, distribution, metabolism or elimination of the study drug. 6. Any other clinically significant laboratory abnormality at the screening visit or prior to the administration of the first dose of study drug. In general, each laboratory value from screening and baseline chemistry and hematology panels should fall within the limits of the normal laboratory reference range, unless deemed not clinically significant by the Investigator. 7. History of or current active tuberculosis (TB) infection; history of latent TB that has not been fully treated or current latent TB infection. 8. Positive serum test for HIV, hepatitis C or hepatitis B virus infection. 9. History of significant allergy to any medication. 10. History of clinically significant alcohol or drug abuse within the past 24 months. 11. Use of any tobacco or nicotine containing product within the previous 12 months. Note: Subjects who are social/occasional smokers may be eligible with Sponsor approval. 12. Administration of any prescription drug (oral contraceptives permitted) within 21 days of study drug administration; or over-the-counter drug (paracetamol and ibuprofen less than or equal to 1 g/day permitted) or herbal, nutritional or vitamin supplement within 7 days of study drug administration, unless Sponsor approval granted. 13. Evidence of drug abuse on urine testing, or a positive test for alcohol. 14. Administration or use of any investigational drug or device within 30 days of study drug administration. 15. Blood or plasma donation within 60 days prior to dosing.
Outcome results
None listed