This trial is conducted in China. The aim of the trial is to investigate safety, tolerability, and pharmacokinetics of the Mulberry Twig Alkaloids tablets (WH006) in healthy ,overweight and obesity subjects.
This is a Phase I clinical trial of safety, tolerability and pharmacokinetics of the Mulberry Twig Alkaloids tablets (WH006) in healthy and overweight or obesity subjects. This trial is divided into three parts: The first part study aims to compare the pharmacokinetics characteristics of WH006 chewing with the first bite of a standardized meal or swallowing after a standardized meal in healthy subjects. The second part study aims to investigate the safety, tolerability and pharmacokinetics of single ascending doses of WH006 in healthy subjects. The third part study aims to investigate the safety, tolerability and pharmacokinetics of multiple ascending doses of WH006 in both healthy participants and overweight or obese subjects.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
62
Part One: Administered by chewing with meals or swallowing after meals, with a dosage of 126 milligrams, given as a single dose only.
Parts Two: Administered by swallowing after meals with four distinct dosage groups.
Part Three: Administered by swallowing after meals with two distinct dosage groups, taken three times daily.
Peking University First Hospital
Beijing, Beijing Municipality, China
All reported adverse events, serious adverse events and the percentage of drug-related adverse events, serious adverse events(Part Two and Part Three)
A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported.
Time frame: Part Two: From Day 1 to Day 4; Part Three: From Day 1 to Day 12.
To compare the Cmax of chewing or swallowing of WH006 with single dose(Part One)
To measure the peak drug concentration of Mulberry Twig Alkaloids(1-deoxynojirimycin(DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol(DAB), Fagomine (FA))with the first bite of a standardized meal or swallowing after a standardized meal
Time frame: Part One: From Day 1 to Day 2, Day 5 to Day 6;
To compare the AUC0-32h of chewing or swallowing of WH006 with single dose(Part One)
To measure the area under the concentration-time curve from time zero to time 32 hours of Mulberry Twig Alkaloids(1-deoxynojirimycin(DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol(DAB), Fagomine (FA))with the first bite of a standardized meal or swallowing after a standardized meal
Time frame: Part One: From Day 1 to Day 2, Day 5 to Day 6;
To compare the AUC0-inf of chewing or swallowing of WH006 with single dose(Part One)
To measure the area under the concentration time curve from time zero to time infinity of Mulberry Twig Alkaloids(1-deoxynojirimycin(DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol(DAB), Fagomine (FA))with the first bite of a standardized meal or swallowing after a standardized meal
Time frame: Part One: From Day 1 to Day 2, Day 5 to Day 6;
To determine the Cmax of WH006 with escalating single dose in healthy subjects(Part Two and Part Three)
To measure the peak drug concentration of Mulberry Twig Alkaloids(1-deoxynojirimycin(DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol(DAB), Fagomine (FA)) with escalating single dose in healthy subjects.
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Part Three: Administered by swallowing after meals with two distinct dosage groups, taken three times daily.
Time frame: Part Two: From Day 1 to Day 2;Part Three: From Day 1 to Day 2, Day 8 to Day 10.
To determine the AUC0-48 of WH006 with escalating single dose in healthy subjects(Part Two and Part Three)
To measure the area under the concentration-time curve from time zero to time 48 hours of Mulberry Twig Alkaloids(1-deoxynojirimycin(DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol(DAB), Fagomine (FA)) with escalating single dose in healthy subjects.
Time frame: Part Two: From Day 1 to Day 2;Part Three: From Day 1 to Day 2, Day 8 to Day 10.
To determine the AUC0-inf of WH006 with escalating single dose in healthy subjects(Part Two and Part Three)
To measure the area under the concentration-time curve from time zero to time infinity of Mulberry Twig Alkaloids(1-deoxynojirimycin(DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol(DAB), Fagomine (FA)) with escalating single dose in healthy subjects.
Time frame: Part Two: From Day 1 to Day 2;Part Three: From Day 1 to Day 2, Day 8 to Day 10.
To determine the Cmax,ss of WH006 with escalating multiple dose in healthy and overweight or obese subjects(Part Three)
To measure the maximum concentration at steady state of Mulberry Twig Alkaloids(1-deoxynojirimycin(DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol(DAB), Fagomine (FA)) with escalating multiple dose in healthy and overweight or obese subjects.
Time frame: Part Three: From Day 1 to Day 10;
To determine the Cmin,ss of WH006 with escalating multiple dose in healthy and overweight or obese subjects(Part Three)
To measure the trough plasma concentration at steady state of Mulberry Twig Alkaloids(1-deoxynojirimycin(DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol(DAB), Fagomine (FA)) with escalating multiple dose in healthy and overweight or obese subjects.
Time frame: Part Three: From Day 1 to Day 10;
To determine the Cav,ss of WH006 with escalating multiple dose in healthy and overweight or obese subjects(Part Three)
To measure the average concentration at steady state of Mulberry Twig Alkaloids(1-deoxynojirimycin(DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol(DAB), Fagomine (FA)) with escalating multiple dose in healthy and overweight or obese subjects.
Time frame: Part Three: From Day 1 to Day 10;
To determine the AUC0-tau of WH006 with escalating multiple dose in healthy and overweight or obese subjects(Part Three)
To measure the area under the concentration-time curve from time zero to 5 hours, 14 hours and 24hours of Mulberry Twig Alkaloids(1-deoxynojirimycin(DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol(DAB), Fagomine (FA)) with escalating multiple dose in healthy and overweight or obese subjects.
Time frame: Part Three: From Day 1 to Day 10;
To determine the Rac of WH006 with escalating multiple dose in healthy and overweight or obese subjects(Part Three)
To calculate the Rac (Cmax), Rac (AUC0-5),the Rac (AUC0-14), the Rac (AUC0-24), the Rac (AUC0-inf) with the ratio of D8 parameters and D1 parameters of Mulberry Twig Alkaloids(1-deoxynojirimycin(DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol(DAB), Fagomine (FA)) with escalating multiple dose in healthy and overweight or obese subjects.
Time frame: Part Three: From Day 1 to Day 10;