A Study to Assess the Safety of MEB-1170 in Healthy Subjects

• Status: Recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objective: To determine the safety and tolerability of single and multiple ascending oral doses of MEB-1170 in healthy subjects.

Secondary Objectives:

1. To determine the single and multiple oral dose pharmacokinetic profiles of MEB-1170 and the primary metabolite, M373, in healthy subjects.

2. To determine the effect of food on the pharmacokinetic (PK) profile of a single oral dose of MEB-1170 in healthy subjects.

3. To assess the pharmacodynamic (PD) response following single and multiple oral doses of MEB-1170

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Mebias Discovery, Inc

Criteria

Inclusion Criteria:

To be eligible for this study, subjects must meet all of the following inclusion criteria:

1. Provides written IRB-approved informed consent prior to any study procedures.

2. Male or female between 18 and 55 years old (inclusive) at the time of screening.

3. In good general health at screening, free from clinically significant unstable medical, surgical or psychiatric illness, at the discretion of the Investigator.

4. Subjects have a BMI between ≥ 18.0 and ≤ 32.0 kg/m2 at screening.

5. Vital signs (measured in supine position after a 5-minute rest) at screening:

1. Systolic blood pressure ≥90 and ≤140 mmHg

2. Diastolic blood pressure ≥50 and ≤ 90 mmHg

3. Heart rate ≥45 and ≤100 bpm

4. Temperature ≥35.5 °C and ≤ 37.5 °C

5. Vital signs may be repeated once, within a minimum of 10 minutes of the completion of the last set of vital signs (while maintaining supine position until the repeated set of vital signs are collected), if it is suspected that falsely high or low levels have been obtained.

6. Adequate venous access to allow collection of multiple blood samples.

7. Negative Covid PCR test upon admission to the CRU.

a. Subjects in Cohort A3 will need a second COVID test prior to admission the CRU for Period 2.

8. No relevant dietary restrictions and willingness to consume standard meals and snacks.

9. Willing to comply with all study procedures and requirements

10. Ability to tolerate the cold pressor test (determined at screening)

11. Women of childbearing potential (WOCBP) must be non-pregnant and non-lactating, and must use two acceptable, highly effective methods of contraception from screening until study completion, including the follow-up period (please see Section 9.4.2 for acceptable methods of contraception). Abstinence as a lifestyle choice is also acceptable. WOCBP must have a negative serum pregnancy test at Screening and negative urine pregnancy test at Day -1 and be willing to have additional pregnancy tests as required throughout the study. WOCBP must also use two acceptable, highly effective methods of contraception from screening until study completion, including the follow-up period and for 30 days after the last dose (please see Section 10.4.2 for acceptable methods of contraception). Women not of childbearing potential must be post menopausal for ≥12 months or be surgically sterile. Hysterectomy with retention of ovary function is permitted. Post-menopausal status will be confirmed through testing of FSH levels ≥ 40 IU/mL at screening for amenorrhoeic female subjects.

12. Male subjects must be surgically sterile (> 30 days since vasectomy per medical history or verbal confirmation), or, if engaged in sexual relations with a WOCBP, the subject and his partner must use two acceptable, highly effective methods of contraception from screening until study completion, including the follow-up period and 30 days after the last dose (please see Section 9.4.2 for acceptable methods of contraception). Abstinence as a lifestyle choice is also acceptable.

Exclusion Criteria:

To be eligible for this study, subjects must not meet any of the following exclusion criteria:

1. Pregnant or lactating at screening or baseline or planning to become pregnant (self or partner) at any time during the study, including the specified follow-up period.

2. History or presence of malignancy at screening or baseline, with the exception of adequately treated localised skin cancer (basal cell or squamous cell carcinoma) or carcinoma in-situ of the cervix.

3. Clinically significant infection within 28 days of the start of dosing, or infections requiring parenteral antibiotics within the 6 months prior to screening.

4. Clinically significant surgical procedure within 3 months of screening, at the discretion of the Investigator.

5. Currently suffering from clinically significant systemic allergic disease at screening or baseline or has a history of significant drug allergies including a history of anaphylactic reaction; allergic reaction due to any drug which led to significant morbidity.

6. Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within 3 months prior to study treatment administration; corticosteroids are permitted at the discretion of the Investigator), or exposure to any significantly immune suppressing drug within 30 days prior to screening or 5 half lives, whichever is longer.

7. History or presence at screening or baseline of a condition associated with significant immunosuppression.

8. Positive test for hepatitis C (HCV), hepatitis B (HBsAg), COVID, or human immunodeficiency virus (HIV) antibody at screening.

9. Symptoms of dysphagia at screening or baseline or known difficulty in swallowing capsules.

10. Any condition at screening or baseline (eg, chronic diarrhea, inflammatory bowel disease or prior surgery of the gastrointestinal tract) that would interfere with drug absorption or any disease or condition that is likely to affect drug metabolism or excretion, at the discretion of the Investigator.

11. History or presence at screening or baseline of clinically significant cardiac arrhythmia or congenital long QT syndrome.

12. QT interval corrected using Fridericia's formula (QTcF) > 450 msec for males or >470 msec for females.

13. Use of tobacco or nicotine containing products in the previous month prior to dosing or a positive urine cotinine test at Screening or Baseline.

14. Lack of willingness to abstain from the consumption of tobacco or nicotine-containing products throughout the duration of the study and until completion of the final Follow-up visit.

15. Regular alcohol consumption defined as > 21 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit or a 125 mL glass of wine) or the subject is unwilling to abstain from alcohol for 48 h prior to admission and 48 h prior to Follow-up study visit.

16. Positive toxicology screening panel [urine test, including qualitative identification of barbiturates, tetrahydrocannabinol (THC), amphetamines, benzodiazepines, opiates and cocaine] or alcohol test (breath or urine) during Screening or at any time during the Study.

17. History of substance abuse or dependency or history of recreational IV drug use, over the last 5 years.

18. Use of any prescription drugs (other than permitted contraception) within 14 days prior to dosing or throughout the duration of the study, without prior approval of the Investigator and written approval of the CRO Medical Monitor.

19. Use of OTC medication including nonsteroidal anti-inflammatory drugs (NSAIDs), herbal remedies, supplements, or vitamins within 7 days prior to dosing. An exception to this is use of acetaminophen up to 4g/day to treat mild discomfort.

20. Use of any investigational drug or device within 30 days or 5 half-lives, whichever is longer, prior to screening.

21. Clinically significant blood loss, or blood or blood product donation >250 mL within 28 days of screening.

22. Subject is unwilling to refrain from strenuous exercise from 7 days prior to admission to the clinical trial unit until completion of the final onsite follow-up visit, where strenuous exercise is defined as a significant increase in the Subject's usual level of physical activity.

23. Any other reason that, in the opinion of the Investigator, might interfere with the evaluation required by the study.