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

NCT06367426 | Recruiting Phase 1 DMC

• 1 other identifier: Pharmacobio
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (19)

• Assessment of safety and tolerability of DDN-A-0101 by monitoring vital signs

  Systolic, diastolic blood pressure (mmHg) measurement to assess vital signs after DDN-A-0101 administration

  through study completion (up to Day 12 for SAD test, Day 25 for MAD test)

• Assessment of safety and tolerability of DDN-A-0101 by monitoring vital signs

  Pulse rate (bpm) measurement to assess vital signs after DDN-A-0101 administration

  through study completion (up to Day 12 for SAD test, Day 25 for MAD test)

• Assessment of safety and tolerability of DDN-A-0101 by monitoring vital signs

  Body temperature (°C) measurement to assess vital signs after DDN-A-0101 administration

  through study completion (up to Day 12 for SAD test, Day 25 for MAD test)

• Assessment of safety and tolerability of DDN-A-0101 by monitoring ECG

  12-ECG electrocardiogram test includes measurement of P-wave (reflecting atrial depolarization), QRS complex (reflecting depolarization of ventricles) and QT interval (reflecting the total duration of ventricular depolarization and repolarization

  through study completion (up to Day 12 for SAD test, Day 25 for MAD test)

• Assessment of safety and tolerability of DDN-A-0101 by C-SSRS measurement

  Columbia-suicide severity rating scale (C-SSRS) includes the measurement of the incidences and severity of suicidal thoughts

  through study completion (up to Day 12 for SAD test, Day 25 for MAD test)

• Assessment of safety and tolerability of DDN-A-0101 by laboratory safety tests

  Laboratory safety tests include hematologic test for white blood cell count

  through study completion (up to Day 12 for SAD test, Day 25 for MAD test)

• Assessment of safety and tolerability of DDN-A-0101 by laboratory safety tests

  Laboratory safety tests include blood chemistry test for measurement of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (unit/liter)

  through study completion (up to Day 12 for SAD test, Day 25 for MAD test)

• Assessment of safety and tolerability of DDN-A-0101 by laboratory safety tests

  Laboratory safety tests include urine test for measurement of albumin/creatinine ratio (mg/g)

  through study completion (up to Day 12 for SAD test, Day 25 for MAD test)

• Assessment of pharmacokinetics of Quercitrin, an indicator of of DDN-A-0101 in plasma

  Area under curve (AUC) in plasma

  up to 48 hour after intervention

• Assessment of pharmacokinetics of Quercitrin in plasma

  Maximum concentration (Cmax) in plasma

  up to 48 hour after intervention

• Assessment of pharmacokinetics of Quercitrin in plasma

  Time to peak drug concentration (Tmax) in plasma

  up to 48 hour after intervention

• Assessment of pharmacokinetics of Quercitrin in plasma

  Half-life in plasma

  up to 48 hour after intervention

• Assessment of pharmacokinetics of Quercitrin in plasma

  Clearance (CL/F) in plasma

  up to 48 hour after intervention

• Assessment of pharmacokinetics of Quercitrin in plasma

  Volume of distribution (V/F) in plasma

  up to 48 hour after intervention

• Assessment of pharmacokinetics of Quercitrin in plasma

  Peak to trough fluctuation ratio (PTF) in plasma

  up to 48 hour after intervention

• Assessment of pharmacokinetics of Quercitrin in plasma

  Accumulation index (AI) in plasma

  up to 48 hour after intervention

• Assessment of pharmacokinetics of Quercitrin in urine

  Total amount of Quercitrin excreted in urine (Ae)

  up to 48 hour after intervention

• Assessment of pharmacokinetics of Quercitrin in urine

  Percentage of Quercitrin excreted in urine (fe)

  up to 48 hour after intervention

• Assessment of pharmacokinetics of Quercitrin in urine

  Renal clearance (CL) of Quercitrin

  up to 48 hour after intervention

Secondary Outcomes (2)

• Assessment of pharmacodynamics of DDN-A-0101 for PART2 MAD test

  up to 24 hour after intervention

• Assessment of pharmacodynamics of DDN-A-0101 for PART2 MAD test

  up to 24 hour after intervention

Study Arms (4)

Experimental: DDN-A-0101 for PART 1

EXPERIMENTAL

DDN-A-0101: various single doses, administered to various cohorts

Drug: DDN-A-0101 (SAD)

Experimental: DDN-A-0101 for PART 2

EXPERIMENTAL

DDN-A-0101: various multiple doses, administered to various cohorts

Drug: DDN-A-0101 (MAD)

Placebo Comparator: Placebo for PART 1

PLACEBO COMPARATOR

DDN-A-0101 matching placebo: various single doses, administered to various cohorts

Drug: Placebo (SAD)

Placebo Comparator: Placebo for PART 2

PLACEBO COMPARATOR

DDN-A-0101 matching placebo: various multiple doses, administered to various cohorts

Drug: Placebo (MAD)

Interventions

DDN-A-0101 (SAD) DRUG

Investigational drug * Development name: DDN-A-0101 * Main ingredient and content: DDN-A-0101 (Houttuynia cordata dry extract, 150.0 mg) * Formulation and properties: Light brown circular film coating tablet * Storage method: airtight container, stored at room temperature (1-30 degree celsius) * Administration method: single dose oral administration (300, 600, 900, 1200, 1500 mg) * Expiration date: 36 months from the date of manufacture

Experimental: DDN-A-0101 for PART 1

DDN-A-0101 (MAD) DRUG

Investigational drug * Development name: DDN-A-0101 * Main ingredient and content: DDN-A-0101 (Houttuynia cordata dry extract, 150.0 mg) * Formulation and properties: Light brown circular film coating tablet * Storage method: airtight container, stored at room temperature (1-30 degree celsius) * Administration method: repeated oral administration (150, 300, 450, 600 mg, 2 times/day, 2 weeks of repeated administration) * Expiration date: 36 months from the date of manufacture

Experimental: DDN-A-0101 for PART 2

Placebo (SAD) DRUG

Placebo drug * Development name: placebo of DDN-A-0101 * Formulation and properties: Light brown circular film coating tablet * Storage method: airtight container, stored at room temperature (1-30 degree celsius) * Administration method: single dose oral administration (300, 600, 900, 1200, 1500 mg) * Expiration date: 36 months from the date of manufacture

Placebo Comparator: Placebo for PART 1

Placebo (MAD) DRUG

Placebo drug * Development name: placebo of DDN-A-0101 * Formulation and properties: Light brown circular film coating tablet * Storage method: airtight container, stored at room temperature (1-30 degree celsius) * Administration method: repeated oral administration (150, 300, 450, 600 mg, 2 times/day, 2 weeks of repeated administration) * Expiration date: 36 months from the date of manufacture

Placebo Comparator: Placebo for PART 2

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• 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.

You may not qualify if:

• 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).
• 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.
• 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.
• 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
• The subject with significant abnormalities in neurological examinations conducted during screening visits.
• 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.
• The subject with clinically significant allergic diseases (excluding mild allergic rhinitis that does not require administration)
• The subject who have a history of drug abuse or are positive for an abuse drug in a urine screening test.
• 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.
• 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.

Sponsors & Collaborators

• Pharmacobio: lead

Study Sites (1)

Seoul National University College of Medicine and Hospital

Seoul, 03080, South Korea

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Sagittal Abdominal Diameter; mycophenolic adenine dinucleotide

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Body Size; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Anthropometry; Investigative Techniques; Physiological Phenomena

Study Officials

• In-Jin Jang, Doctor

  Seoul National University College of Medicine and Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

In-Jin Jang, Doctor

CONTACT

82-2-740-8290; ijjang@snu.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: To maintain double-blindness, DDN-A-0101 tablets and placebo with the same formulation and properties that cannot be distinguished in appearance will be used, and sub-packaging will also be the same.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2024
• First Posted: April 16, 2024
• Study Start: April 1, 2024
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: April 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)