A Phase I Study of DDN-A-0101 in Healthy Volunteers and Elder People

A Dose-blocked-randomized, Double-blind, Placebo-controlled, Single and Multiple Dosing, Dose-escalation Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of DDN-A-0101 in Healthy Adults and Elderly Subjects

The study is a Phase I, randomized double-blind, placebo-controlled, single and multiple dosing, dose-escalation study of the oral administration of DDN-A-0101 in healthy adults and elderly subjects

The study includes two Parts; Part1 includes single ascending dose study (SAD) and Part2 includes multiple ascending dose study (MAD). Approximately 50 subjects will be enrolled in the SAD and MAD respectively. New subjects will be recruited for each cohort in both Parts. The SAD Part will include 5 dose levels (S1, S2, S3, S4, S5) and cohort S3 will proceed to food effect cohort. The MAD Part will include 5 dose levels (M1, M2, ME, M3, M4) and cohort ME will be performed in the elderly group.

Inclusion Criteria:

1. The subject is a healthy adult over 19 years of age and under 65 years of age*.

   *For cohort ME (senior aged person), over 65 years old and under 75 years old a healthy volunteer

2. As a result of the body measurement at the time of screening, the subject has the body weight of 55.0 kg or more and 90.0 kg or less, and the body mass index (BMI) is 18.0 kg/m2 or more and 27.0 kg/m2 or less.

3. The subject who has listened to and listened to sufficient explanations of this clinical trial and voluntarily decided to participate in writing to faithfully implement the compliance with the clinical trial.

Exclusion Criteria:

1. The subject with a history of clinically significant cardiovascular system, respiratory system, kidney, endocrine system, blood system, digestive system, central nervous system, urinary system, musculoskeletal system, psychiatric disease (mood disorders, obsessive-compulsive disorders, etc.) or malignancies (but can be registered if the past history of complete recovery does not affect the current health condition).

2. The subject with a history of gastrointestinal diseases (such as Crohn's disease, ulcers, acute or chronic pancreatitis, hypothyroidism, anaphylaxis, etc.) or gastrointestinal operations (except simple appendectomy or hernia) that may affect the absorption of clinical trials drugs.

3. The subject diagnosed with peptic ulcer, esophageal disease, and Zollinger-Ellison syndrome within 90 days prior to clinical trial drug administration and have been treated or have a medical history or symptoms clinically suspicious of it.

4. The subject showing the following values in the laboratory test results.

   • Blood aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 1.5 times normal upper limit
   • Blood Total bilirubin level > 1.5 times normal upper limit
   • Blood creatine phosphokinase (CPK) level > 1.5 times normal upper limit
   • Positive serum epidemiological test results (human immunodeficiency virus (HIV) Ag/Ab, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) Ab, Syphilis regain test)
   • Chronic kidney disease epidemiology collaboration (CKD-EPI) equation calculated creatine cleaning rate: < 60 mL/min/1.73 m2

5. The subject with significant abnormalities in neurological examinations conducted during screening visits.

6. The subject who showed systolic blood pressure ≥ 150 mmHg or < 90 mmHg, diastolic blood pressure ≥ 100 mmHg or < 50 mmHg in blood pressure measured from the upper left after resting for at least 5 minutes at the time of screening.

7. The subject with clinically significant allergic diseases (excluding mild allergic rhinitis that does not require administration)

8. The subject who have a history of drug abuse or are positive for an abuse drug in a urine screening test.

9. The subject who have a history of hypersensitivity reactions to drugs of the same class as the main ingredient and component components of clinical trial drugs.

10. The subject who have received medications from other clinical trials and biological equivalence trials within 6 months of the start of administration of clinical trials.

11. The subject who took metabolic enzyme-induced and inhibitory drugs such as barbital drugs within 30 days prior to administration of clinical trial drugs.

12. The subject who have donated whole blood within 60 days prior to administration of clinical trial drugs or volunteers who have donated or received component blood within 20 days prior to administration of clinical trial drugs.

13. The subject who took over-the-counter drugs or herbal medicines within 14 days of clinical trial administration, or took over-the-counter drugs, health functional foods, or vitamins within 7 days (but may participate in clinical trials if it is deemed that the results of the clinical trial are not affected by the examiner's judgment).

14. The subject who cannot prohibit the administration of the following drugs during the clinical trial period from 8 weeks before the scheduled date of the first administration of the drug for clinical trial.

    • Dementia medications, cognitive enhancers, choline agonists, anti-choline agonists, anti-Parkinson drugs
    • Medicines/supplements/health functional foods and other cosmetics (shampoo, lotion, etc.) containing Houttuynia cordata extract, the main ingredient of this clinical trial drug
    • Medicines or health functional foods with similar indications to other clinical medicines (e.g., extracts derived from ginkgo leaves, etc.)

15. The subject who consumed grapefruit-containing food (one grapefruit or more than 200 ml of grapefruit juice) within 7 days prior to administration of clinical trial drugs.

16. The subject who are forced to consume caffeine (coffee, green tea, etc. >5 cups/day) continuously or consume caffeine-containing food 24 hours before hospitalization during the clinical trial period.

17. The subject who are unable to drink alcohol continuously (alcohol > 210 g/shareholder) or abstain from drinking during clinical trials 24 hours before hospitalization.

18. The subject who cannot smoke excessively (tobacco > 10 skins/day) or quit smoking during the clinical trial period from 24 hours before hospitalization

19. The subject who is pregnant or breast-feeding.

20. The subject who do not agree to use one or more medically acceptable forms of contraception during the pre-clinical period and until at least 90 days after the last clinical trial administration, and those who do not agree to donate sperm or eggs until at least 90 days after the last clinical trial administration. Medically acceptable forms of contraception are as follows.

    • Use of an intrauterine device with proven pregnancy failure rates in the person or partner
    • Use both blocking contraceptives (for male or female use) and spermicide
    • Surgery by yourself or your partner (vasectomy, salpingectomy/ligation, hysterectomy)

21. The subject with a history of suicidal behavior and/or ongoing suicidal ideation following C-SSRS evaluation when screening.

22. The subject deemed unsuitable for participation in clinical trials due to other reasons other than the criteria for exclusion above.