A Phase 1 Safety and Tolerability Study of TML-6 in Healthy and Elderly Volunteers for Alzheimer's Disease Treatment

NCT06562114 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MELTMLZ20220315
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, single-ascending dose (SAD), multiple-ascending dose (MAD), food effect, and pharmacokinetic (PK) Study of TML-6.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability: Incidence of Serious Adverse Events (SAEs) and treatment-related adverse events

  Incidence of SAEs and treatment-related severe AEs

  All subjects at each dose level complete the 3-day safety assessments post-dose for part 1-3 study and all subjects at each dose level complete the 8-day safety assessments post the first dose for part 4 & 5 study

Secondary Outcomes (13)

• Plasma PK: Maximum Plasma Concentration (Cmax) will be assessed for part 1-5 study

  Predose, 0.5, 1, 2, 4, 8, 12, 16, 24, and 48 hours postdose

• Plasma PK: Area Under the Curve (AUC) will be assessed for part 1-5 study

  Predose, 0.5, 1, 2, 4, 8, 12, 16, 24, and 48 hours postdose

• Plasma PK: Time to reach peak plasma concentration (Tmax) will be assessed for part 1-5 study

  Predose, 0.5, 1, 2, 4, 8, 12, 16, 24, and 48 hours postdose

• Plasma PK: Terminal half-life (T1/2) will be assessed for part 1-5 study

  Predose, 0.5, 1, 2, 4, 8, 12, 16, 24, and 48 hours postdose

• Plasma PK: Peak plasma concentration at steady state (Cmax,ss) will be assessed for part 4 and 5 study

  predose, 0.5, 1, 2, 4, 8, 12, 16, and 24 hours postdose; Day 3: predose; Day 4:predose; Day 5:predose; Day 6: predose; Day7: predose, 0.5, 1, 2, 4, 8, 12, 16, and 24 hours postdose

Study Arms (2)

TML-6 Granules

EXPERIMENTAL

This study consists of 5 parts, Part 1 (SAD): 5 cohorts of subjects are planned to be orally dosed, ranging from 100 mg - 1000 mg. Part 2 (Food effect): All subjects in Cohort 2 of Part 1 will constitute Period 1 of Part 2 and will move to Period 2 to receive the same Investigational Product (IP) dose as in Period 1. Part 3 (Elderly): One cohort of elderly subjects will receive a single dose of IP. A dose level of IP within the safe range defined in the Part 1 SAD study will be chosen Part 4 (MAD): 2 cohorts of subjects are planned to be orally dosed once daily for 7 consecutive days, ranging from 400 mg - 800 mg. Part 5 (MAD+Cerebrospinal Fluid, CSF PK): One cohort of elderly subjects will receive orally once daily for 7 consecutive days of IP. The dose level of IP defined in the Part 4 MAD study will be chosen.

Drug: TML-6 Granules

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

TML-6 Granules DRUG

Administered orally

TML-6 Granules

Placebo DRUG

Administered orally

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male and female volunteers
• For Parts 1, 2, and 4 (Cohorts 1-5 and 7-8): Subject's age is ≥18 years old and ≤55 years old at screening.
• For Parts 3 and 5 (Cohorts 6 and 9): Subject's age is ≥60 years old and ≤80 years old at screening.
• For Parts 1, 2, and 4 (Cohorts 1-5 and 7-8): Subjects whose body mass index (BMI) at screening is within a range of ≥18.5 kg/m2 and \<30.0 kg/m2 For Parts 3 and 5 (Cohorts 6 and 9): Subjects whose BMI \<30.0 kg/m2 Note: BMI = Body weight (kg) / \[Height (m)\]2; Body weight is not less than 50 kg at screening and admission.
• Subjects who are deemed to be satisfactory health by the investigator through an assessment of their medical history, physical examinations, and routine laboratory tests.
• Female subjects of child-bearing potential show negative pregnancy test results at screening and admission.
• Female subjects of child-bearing potential, committing to practicing sexual abstinence or using and continue to use 2 highly effective contraceptives of birth control for at least 30 days prior to screening (that period will extend to 90 days for oral contraceptive use) and for at least 30 days after the last dose of investigational product (IP).
• For a subject to be considered not to be of child-bearing potential, she must have been amenorrheic for at least 12 months with confirmed follicle-stimulating hormone (FSH) level (within postmenopausal range) at screening, or must have had a hysterectomy, a bilateral tubal ligation, and/or a bilateral oophorectomy (as determined by the medical history).
• The male partner of a female study subject with childbearing potential must use a condom and ensure that his partner uses a highly effective contraception as outlined below.
• The highly effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
• Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject.
• Combination of the following listed methods (d.1+d.2):
• d.1. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception, intrauterine device (IUD), or intrauterine system (IUS).

You may not qualify if:

• Subjects with any properly diagnosed disease within 30 days prior to the first dose of the IP.
• Subjects who have a QTcF interval \>450 msec (male) or \>470 msec (female) (Fridericia's correction) at screening. The assessment may be repeated once during the screening period.
• Systolic blood pressure (SBP) \>140 mmHg or diastolic blood pressure (DBP) \>90 mmHg at screening and admission, irrespective of anti-hypertensive medication status for the subject. The assessments may be repeated for confirmation after resting for approximately 10 to 30 minutes.
• Any laboratory values with the following deviations at screening and admission. The laboratory test may be repeated once during the screening period and Day -1.
• White blood cell count (WBC) \< 3000/μL
• Hemoglobin \< 10 g/dL
• Platelet count \< 100000/μL
• Creatinine \> upper limit of normal (ULN)
• Alanine Aminotransferase (ALT) \> ULN
• Aspartate Aminotransferase (AST) \> ULN
• Total bilirubin \> ULN of the reference range \* If agreement is obtained per the investigator's discretion, exceptions may be made for isolated ALT or AST elevation \<1.5× ULN and bilirubin values that are above the ULN for subject has an underlying diagnosis of Gilbert's syndrome.
• Subjects who have been tested positive for the following tests:
• \- Human immunodeficiency virus (HIV)
• \- Hepatitis B virus (HBV)
• \- Hepatitis C virus (HCV)

Sponsors & Collaborators

• Merry Life Biomedical Co., Ltd.: lead

Study Sites (1)

Parexel International

Glendale, California, 91206, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2024
• First Posted: August 20, 2024
• Study Start: July 11, 2024
• Primary Completion: July 18, 2025
• Study Completion: August 15, 2025
• Last Updated: October 30, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)