A Phase 1, Safety, Tolerability, Single-ascending Dose, Multiple-ascending Dose, Food Effect, and Pharmacokinetic Study of TML-6 in Healthy Volunteers

Merry Life Biomedical Co., Ltd.1 site in 1 country72 target enrollmentJuly 11, 2024

ConditionsHealthy

InterventionsTML-6 Granules Placebo

DrugsTML-6 Granules Placebo

Overview

Phase: Phase 1
Intervention: TML-6 Granules
Conditions: Healthy
Sponsor: Merry Life Biomedical Co., Ltd.
Enrollment: 72
Locations: 1
Primary Endpoint: Safety and tolerability: Incidence of Serious Adverse Events (SAEs) and treatment-related adverse events
Status: Completed
Last Updated: 6 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

July 11, 2024

End Date

August 15, 2025

Last Updated

6 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Merry Life Biomedical Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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:

Exclusion Criteria

•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 -
•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

Arms & Interventions

TML-6 Granules

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.

Intervention: TML-6 Granules

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

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

Time Frame: 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

Incidence of SAEs and treatment-related severe AEs

Secondary Outcomes

Plasma PK: Terminal half-life at steady state (T1/2,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)
CSF PK: Time to reach peak concentration in CSF at steady state (Tmax,ss) will be assessed for part 5 study(on Day 7 (prior to dosing, 0.5, 1, 2, 4, 8, 12, 16 hours after dosing) and Day 8 (24 hours after dosing))
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)
Plasma PK: Area under the concentration-time curve (AUC0→24,ss and AUC0→τ,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)
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: Accumulation ration (Rac) 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)
CSF PK: Area under the CSF concentration-time curve from 0 to the 24 hours at steady state (CSF AUC0→24,ss) will be assessed for 5 study, if applicable(on Day 7 (prior to dosing, 0.5, 1, 2, 4, 8, 12, 16 hours after dosing) and Day 8 (24 hours after dosing))
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)
CSF PK: Maximum observed concentration in CSF at steady state (CSF Cmax,ss) will be assessed for part 5 study(on Day 7 (prior to dosing, 0.5, 1, 2, 4, 8, 12, 16 hours after dosing) and Day 8 (24 hours after dosing))
CSF PK: Ratio of CSF AUC0→24,ss to Plasma AUC0→24,ss for part 5 study, if applicable(on Day 7 (prior to dosing, 0.5, 1, 2, 4, 8, 12, 16 hours after dosing) and Day 8 (24 hours after dosing))
Plasma PK: Time to reach peak concentration at steady state (Tmax,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)