A Phase 1 Safety and Tolerability Study of TML-6 in Healthy and Elderly Volunteers for Alzheimer's Disease Treatment
NCT Number: NCT06562114
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Healthy
Interventions: DRUG: TML-6 Granules|DRUG: Placebo
Sponsor: Merry Life Biomedical Co., Ltd.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 72
Study Design: Allocation: RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-07-11
Completion Date: 2025-07
Locations: Parexel International, Glendale, California, 91206, United States

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.

Primary Outcome Measures: 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 Outcome Measures: Plasma PK: Maximum Plasma Concentration (Cmax) will be assessed for part 1-5 study, Part 1-5 study (plasma PK):

• Peak plasma concentration (PCmax,) \[ng/mL\] of TML-6

Part 2 only:

Comparative bioavailability analysis in the extent of the peak concentration (PCmax)\[ng/mL\] of TML-6 under fed or fasting condition, 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, Part 1-5 study (plasma PK):

The TML-6 plasma concentration-time profile will be established and Area under the concentration-time curve (AUC0→24, AUC0→last, 0→inf, and %AUCextrap)\[ng\*h/mL\] of TML-6

Part 2 only:

Comparative bioavailability analysis in the extent of total exposure by area under the curve (AUC0→last and AUC0→inf) \[ng\*h/mL\] of TML-6 under fed or fasting condition, 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, Part 1-5 study (plasma PK):

• Time to reach peak plasma concentration (Tmax)\[hours, or h\] of TML-6

Part 2 only:

Comparative bioavailability analysis in the extent of the Time to reach peak concentration (Tmax)\[hours, or h\] of TML-6 under fed or fasting condition, 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, Part 1-5 study (plasma PK):

• Terminal half-life (T1/2) \[hour\] of TML-6

Part 2 only:

Comparative bioavailability analysis in the extent of Terminal half-life (T1/2) \[hour\] of TML-6 under fed or fasting condition, 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, Part 4-5 study (plasma PK):

• Peak plasma concentration at steady state (Cmax,ss)\[ng/mL\] of TML-6, 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, Part 4-5 study (plasma PK):

• Area under the concentration-time curve at steady state (AUC0→24,ss and AUC0→τ,ss) \[ng\*h/mL\] of TML-6, 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 concentration at steady state (Tmax,ss) will be assessed for part 4 and 5 study, Part 4-5 study (plasma PK):

• Time to reach peak concentration at steady state (Tmax,ss) \[hours, or h\] of TML-6, 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: Terminal half-life at steady state (T1/2,ss) will be assessed for part 4 and 5 study, Part 4-5 study (plasma PK):

• Terminal half-life at steady state (T1/2,ss) \[hour\] of TML-6, 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: Accumulation ration (Rac) will be assessed for part 4 and 5 study, Part 4-5 study (plasma PK):

• Accumulation ration (Rac) \[unit of ratio\] of TML-6, 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: Maximum observed concentration in CSF at steady state (CSF Cmax,ss) will be assessed for part 5 study, CSF PK at steady-state (after the final dose)

• Maximum observed concentration in CSF at steady state (CSF Cmax,ss)\[ng/mL\] of TML-6, 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: Time to reach peak concentration in CSF at steady state (Tmax,ss) will be assessed for part 5 study, CSF PK at steady-state (after the final dose),

• Time to reach peak concentration in CSF at steady state (Tmax,ss) \[hours, or h\] of TML-6, 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: 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, CSF PK at steady-state (after the final dose),

• Area under the CSF concentration-time curve from 0 to the 24 hours at steady state (CSF AUC0→24,ss)\[ng\*h/mL\] of TML-6, 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)|CSF PK: Ratio of CSF AUC0→24,ss to Plasma AUC0→24,ss for part 5 study, if applicable, • Ratio of CSF AUC0→24,ss to Plasma AUC0→24,ss\[unit of ratio\] of TML-6, 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)