Single Ascending Dose and Multiple Ascending Dose Evaluation of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MDI-2517 in Healthy Participants

MDI Therapeutics, Inc.

Status and phase: Enrolling; Phase 1

Conditions: Safety After Oral Intake

Treatments: Other: Placebo; Drug: MDI-2517 3600mg; Drug: MDI-2517 1600mg; Drug: MDI-2517 2400mg; Drug: MDI-2517 800mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT07220889

MDI-2517-01-002

Details and patient eligibility

About

The goal of this clinical trial is to learn if drug MDI2517 is safe and to learn more about its drug effects in healthy participants. Healthy participants will take single or multiple doses of drug and the safety and drug levels will be measured.

Full description

The goal of this clinical trial is to learn if drug MDI2517 is safe and to learn more about its drug effects in healthy participants. Healthy participants will take single or multiple doses of drug and the safety and drug levels will be measured. Healthy participants will be monitored for adverse events, laboratory test changes, changes in vital signs, electrocardiogram and the plasma drug levels will be measured. The amount of the drug and its metabolites in urine and blood will be measured. Blood and urine will be used to evaluate the effects of MDI-2517.

Enrollment: 52 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Capable to understand the study procedures and providing signed informed consent as described Section 8.2, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Healthy male and female participants 18 to 55 years of age inclusive, at the time of signing the informed consent.
3. Body weight of a minimum 50 kg for men and 45 kg for women and body mass index (BMI) within the range of 18.5 to 32 kg/m2
4. Participants who are generally healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring.
5. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Female participants should be of nonchildbearing potential (postmenopausal i.e., spontaneous amenorrhea for at least 12 months prior to dosing with confirmatory follicle-stimulating hormone [FSH] > 40 mIU/mL, or premenopausal and surgically sterilized), or of childbearing potential who agree to take highly effective contraceptive measures throughout the trial (see Section 11.15 for highly effective contraceptive guidance). Sexually active female participants of childbearing potential with non-sterile male partners, and sexually active non-surgically sterile male participants with female partners of childbearing potential will be required to use highly effective double contraceptive method. Women of childbearing potential and those with less than 24 weeks from menopause must undergo a urine pregnancy test at screening and result must be negative.
6. Ability to refrain from consumption of Seville oranges, grapefruit or grapefruit juice, pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices from 7 days before participants check into the clinical site until collection of the final PK sample for each participant.
7. Ability to abstain from ingesting caffeine- or xanthine-containing products (eg, coffee, black/green tea, cola drinks, and chocolate) or energy drinks for 48 hours before participants check into the clinical site until after collection of the final PK and/or PD sample.
8. Ability to abstain from alcohol for 24 hours before admission to the clinical site until after collection of the final PK and/or PD sample.
9. Ability to swallow multiple tablets within a 10 minute window.

Exclusion criteria

1. Major medical illness or unstable medical condition within 6 months of screening that in the opinion of the investigator may interfere with the participant's ability to comply with study procedures and abide by study restrictions, or with the ability to interpret safety data that would prevent completion of study procedures or assessments.

2. Any clinically significant abnormal finding at Screening during the physical examination or a clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.

3. Chronic or ongoing active infectious disease requiring systemic treatment including, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, and tuberculosis.

4. Any acute infections within 14 days of screening.

5. Live attenuated vaccines received within 1 month of screening. Other vaccines, including coronavirus 2019 (COVID-19) vaccine, within 14 days prior to Screening.

6. Participants known or suspected of not being able to comply with this study protocol (eg, due to alcoholism, drug dependency or psychological disorder)

7. Laboratory values as follows:

   1. Any clinically significant lab abnormalities
   2. AST or ALT; > the upper limit of normal (ULN)
   3. Total bilirubin > 1.5 times ULN (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is < 35%)
   4. Platelet counts < 150 × 109/L or > 450 × 109/L
   5. Hemoglobin outside of normal limits
   6. Coagulation tests (prothrombin time, partial thromboplastin time) outside of normal limits

8. Screening corrected QT interval (QTc) > 450 milliseconds for males and > 470 ms for females. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), machine read or manually overread.

9. Screening estimated glomerular filtration rate (eGFR) using 2021 CKD-EPI method <90 mL/min/1.73m2

10. Positive serology test results for Hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen and antibody at screening. Positive evaluation for COVID-19 infection.

11. History of significant allergic reactions (eg, anaphylactic reaction, hypersensitivity, angioedema) to any drug.

12. Use of prescription or nonprescription drugs, including vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication through the final study visit, unless in the opinion of the investigator and Medical Monitor the medication will not interfere with the study procedures or compromise participant safety with the exception of oral contraception or the occasional use of acetaminophen (up to 2 g daily). Use of monoamine oxidase inhibitors and St. John's Wort within 30 days of dosing.

13. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs, eg, acetylsalicylic acid) or selective serotonin reuptake inhibitors within 7 days prior to screening through the final study visit.

14. Use of tobacco products or uses other nicotine-containing products (eg, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, inhalers or vapes) from 3 months before screening until final follow-up visit. Use of cigarettes 3 months before screening until final visit.

15. History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 7 units for women or 14 units for men of alcohol per week (1 unit = 340 mL of beer 5%, 140 mL of wine 12%, or 45 mL of distilled alcohol 40%) through the final study visit.

16. History of drug abuse within 1 year prior to screening or recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening through the final study visit.

17. History of hypersensitivity to platelet concentrates or human plasma proteins.

18. Any type of known platelet function disorder.

19. Individuals with increased risk of thrombotic events (eg, history of pulmonary embolism or thrombosis).

20. Any blood product donation given or received within 3 weeks of screening or loss of 500 mL or more of whole blood within 8 weeks prior to dosing.

21. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration. Previously received MDI-2517 study drug or placebo in this study.

22. Positive pregnancy test or lactating female participant

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

---

52 participants in 5 patient groups

SAD 1

Active Comparator group

Description:

SAD cohort 1 will receive a single oral dose of 2400 mg of MDI-2517 or matching placebo

Treatment:

Drug: MDI-2517 2400mg

Other: Placebo

SAD 2

Active Comparator group

Description:

SAD cohort 2 will receive a single oral dose up to 3600 mg of MDI-2517 or matching placebo.

Treatment:

Drug: MDI-2517 3600mg

Other: Placebo

MAD 1

Active Comparator group

Description:

MAD cohort 1 will receive a total daily dose of 800 mg of MDI-2517 or matching placebo administered either once daily (QD) or twice daily (BID).

Treatment:

Drug: MDI-2517 800mg

Other: Placebo

MAD 2

Active Comparator group

Description:

MAD cohort 2 will receive a total daily dose of up to 1600 mg of MDI-2517 or matching placebo administered either QD or BID.

Treatment:

Drug: MDI-2517 1600mg

Other: Placebo

MAD 3

Active Comparator group

Description:

MAD cohort 3 will receive a total daily dose of up to 2400 mg of MDI-2517 or matching placebo administered either QD or BID.

Treatment:

Drug: MDI-2517 2400mg

Other: Placebo