Researchers will evaluate the safety, tolerability, and pharmacokinetics (PK) of orally administered Amisodin in healthy adult subjects through a randomized, double-blind, placebo-controlled Phase 1 study consisting of two parts: single ascending dose (SAD) and multiple ascending dose (MAD). The food effect will be assessed in one cohort in Part1. Approximately 32 healthy, adult subjects are planned to be enrolled in total. Subjects will participate in only one part and one cohort.
During this trial, a total of 32 subjects will be randomized in a 3:1 ratio (out of 8 subjects, 6 on Amisodin, 2 on placebo in each dose group). The placebo is a capsule that looks like Amisodin but contains no study drug. The use of a placebo helps to make sure that any side effects during the study are judged fairly. In Part 1 (SAD), subjects will receive a single oral dose of Amisodin or placebo under fasting conditions, with one cohort crossing over to receive the same treatment under fed conditions to assess the effect of food. In Part 2 (MAD), subjects will receive Amisodin or placebo once daily for 7 days under fasting conditions. Dose escalation in both parts will proceed only after safety and tolerability are confirmed by the Safety Review Committee (SRC). Safety assessments will include adverse events (AEs), ECGs, vital signs, laboratory tests, physical examinations, and C-SSRS evaluations, while plasma samples will be collected to evaluate PK. Amisodin will be administered study drug or placebo with approximately 180mL of water under fasting conditions. The capsules will be opened and mixed with 60mL of water. The contents will be stirred well to create a uniform suspension for consumption and immediately administered orally as one dose to the subject. The cup/bottle will be rinsed with an additional 60mL of water and immediately administered to the subject. A second rinse with an additional 60mL of water will be performed and immediately administered to the subject.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
32
Pharmaron, Inc.
Baltimore, Maryland, United States
RECRUITINGNumber and severity of TEAEs following a single oral dose of Amisodin and placebo.
To evaluate the safety and tolerability of a single ascending dose of Amisodin in healthy adult subjects.
Time frame: From signing of the informed consent form until the follow-up visit (7 days [± 1 day] after dosing).
Pharmacokinetics (PK) of Amisodin
AUC0-t-The area under the concentration-time curve, from time 0 to the last observed non-zero concentration, as calculated by the linear trapezoidal method.
Time frame: SAD- Day 1 to Day 4 MAD- Day 1
Pharmacokinetics (PK) of Amisodin
AUC0-inf -The area under the concentration-time curve from time 0 extrapolated to infinity. AUC0-inf is calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant.
Time frame: SAD- Day 1 to Day 4
Pharmacokinetics (PK) of Amisodin
AUC%extrap -Percent of AUC0-inf extrapolated, represented as (1 - AUC-t/AUC-inf) ×100.
Time frame: SAD- Day 1 to Day 4
Pharmacokinetics (PK) of Amisodin
CL/F - Apparent total plasma clearance after oral (extravascular) administration, calculated as Dose/AUC0-inf.
Time frame: SAD- Day 1 to Day 4
Pharmacokinetics (PK) of Amisodin
Cmax-Maximum observed concentration.
Time frame: SAD- Day 1 to Day 4 MAD- Day 1
Pharmacokinetics (PK) of Amisodin
Tmax -Time to reach Cmax. If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value.
Time frame: SAD- Day 1 to Day 4 MAD- Day 1
Pharmacokinetics (PK) of Amisodin
Tlag-Lag time- the delay between study drug administration and the onset of absorption (applicable to FE Cohort S2 only).
Time frame: SAD- Day 1 to Day 4
Pharmacokinetics (PK) of Amisodin
Kel -Apparent first-order terminal elimination rate constant calculated from a semi log plot of the plasma concentration versus time curve. The parameter will be calculated by linear least-squares regression analysis using the maximum number of points in the terminal log-linear phase (e.g., three or more non-zero plasma concentrations).
Time frame: SAD- Day 1 to Day 4 MAD- Day 7
Pharmacokinetics (PK) of Amisodin
t1/2 -Apparent first-order terminal elimination half-life will be calculated as 0.693/Kel.
Time frame: SAD- Day 1 to Day 4 MAD- Day 7
Pharmacokinetics (PK) of Amisodin
Vz/F -Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration, calculated as Dose/(AUC0-inf × Kel).
Time frame: SAD- Day 1 to Day 4
Pharmacokinetics (PK) of Amisodin
Ctrough-Plasma trough concentration observed at the end of the dosing interval
Time frame: MAD- Day 1 to Day 7
Pharmacokinetics (PK) of Amisodin
AUCtau -The area under the concentration-time curve during a dosing interval (tau) at steady state.
Time frame: MAD- Day 7
Pharmacokinetics (PK) of Amisodin
Cmax,ss-Maximum observed concentration at steady state.
Time frame: MAD- Day 7
Pharmacokinetics (PK) of Amisodin
Cmin,ss-Minimum observed/measured non-zero concentration at steady state.
Time frame: MAD- Day 7
Pharmacokinetics (PK) of Amisodin
Tmax,ss-Time to reach Cmax,ss over the final dosing interval. If the maximum value occurs at more than one time point, Tmax,ss is defined as the first time point with this value.
Time frame: MAD- Day 7
Pharmacokinetics (PK) of Amisodin
CLss/F-Apparent total plasma clearance at steady state after oral (extravascular) administration, calculated as Dose/AUCtau.
Time frame: MAD- Day 7
Pharmacokinetics (PK) of Amisodin
Cavg-Average plasma concentration during the dosing interval (Ratio of AUCtau to the dosing interval, tau).
Time frame: MAD- Day 7
Pharmacokinetics (PK) of Amisodin
Vz,ss/F-Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration, calculated as Dose/(AUCtau × Kel).
Time frame: MAD- Day 7
Pharmacokinetics (PK) of Amisodin
RA\_AUC Accumulation ratio calculated from AUCtau at steady-state and AUC0-t, following a single dose on Day 1. If AUC0-12 on Day 1 cannot be estimated, then corresponding AUC0-t values on Days 1 and 10 will be used instead (will be calculated where applicable).
Time frame: MAD- Day 7
Pharmacokinetics (PK) of Amisodin
RA\_Cmax-Accumulation ratio calculated from Cmax,ss at steady-state and Cmax following a single dose on Day 1.
Time frame: MAD- Day 7
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