This is a single-center, double-blind, single-dose escalation study in healthy volunteers.
This is a single-center, double-blind, single-dose escalation study in healthy volunteers consisting of a 14-day Screening Period, 1-day Predose period, a 2-day Dosing and Evaluation Period, and a 5-day Follow-up Period, with a single Follow-up call scheduled on Day 7 ± 1. Subjects will be confined to the study site for up to 3 days (admitted on Day -1 and discharged on Day 2 or 3, depending on cohort) and will be monitored for adverse events (AEs) and dose limiting toxicities (DLT) during the Dosing, Evaluation and Follow-up Periods. Subjects will also be monitored for concomitant medications and use of rescue medications throughout the study. Subjects will be allocated 1:4 to receive an infusion of saline control (0.9% saline for injection) or Shenqi Fuzheng Injection(SQ-001) continuously for about 1-4 hours. SQ 001 will be administered by intravenous route at a rate of 3 mL/min to one of four final dosages: Cohort 1 (125 mL/day/person), Cohort 2 (250 mL/day/person), Cohort 3 (500 mL/day/person), and Cohort 4 (625 mL/day/person). Each cohort will be enrolled sequentially. Per cohort, three subjects will be dosed initially on Day 1 and observed for 24 hours. If there are no observed AEs that meet the criteria under Stopping Rules, the remaining 7 subjects/cohort will be dosed. Dose escalation to the next higher dose will be based on the observation of results in safety and degree of AEs from the previous cohort and discussion between the Investigator and Sponsor. A maximum 17 PK samples will be collected over the course of the study in each cohort. The PK sampling time points will be grouped as (a) pre-infusion; (b) intra-infusion; (c) completion of infusion; and (d) post-infusion. See Table 10 for plasma PK sampling times. The last PK sample will be collected 24 hours after the end of infusion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
40
SQ001 125mL/day will be administered by intravenous route at a rate of 3 mL/minute
SQ001 250mL/day will be administered by intravenous route at a rate of 3 mL/minute
SQ001 500mL/day will be administered by intravenous route at a rate of 3 mL/minute
Clinical Pharmacology of Miami, Inc.
Miami, Florida, United States
The maximum observed concentrations (Cmax)(ng/mL)
To compare the Cmax of 3 major representative (sentinel) compounds astragaloside IV, calycosin 7-O-β-glucopyranoside, and lobetyolin in different experimental arms
Time frame: On 1 and 2 days (dosing day and the following evaluation day)
Time to reach Cmax (Tmax)(h)
To compare the Tmax of 3 major representative (sentinel) compounds astragaloside IV, calycosin 7-O-β-glucopyranoside, and lobetyolin in different experimental arms
Time frame: On 1 and 2 days (dosing day and the following evaluation day)
Area under the concentration-time curve (AUC)(ng·h/mL)
To compare the AUC of 3 major representative (sentinel) compounds astragaloside IV, calycosin 7-O-β-glucopyranoside, and lobetyolin in different experimental arms
Time frame: On 1 and 2 days (dosing day and the following evaluation day)
Elimination half-life (T1/2)(h)
To compare the Cmax of 3 major representative (sentinel) compounds astragaloside IV, calycosin 7-O-β-glucopyranoside, and lobetyolin in different experimental arms
Time frame: On 1 and 2 days (dosing day and the following evaluation day)
Apparent clearance (CL)(mL/min/kg)
To compare the CL of 3 major representative (sentinel) compounds astragaloside IV, calycosin 7-O-β-glucopyranoside, and lobetyolinin different experimental arms
Time frame: On 1 and 2 days (dosing day and the following evaluation day)
Volume of distribution at steady state (Vdss)(L/kg)
To compare the Vdss of 3 major representative (sentinel) compounds astragaloside IV, calycosin 7-O-β-glucopyranoside, and lobetyolinin different experimental arms
Time frame: On 1 and 2 days (dosing day and the following evaluation day)
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SQ001 625mL/day will be administered by intravenous route at a rate of 3 mL/minute
Saline 0.9% will be administered by intravenous route at a rate of 3 mL/minute
Incidence of treatment-related adverse events
Incidence of treatment-related adverse events as assessed by CTCAE v4.03
Time frame: From predose to up 5 days following the dosing and evaluation period
Frequency of treatment-related adverse events
Frequency of treatment-related adverse events as assessed by CTCAE v4.03
Time frame: From predose to up to 5 days following the dosing and evaluation period
Grade of treatment-related adverse events
Grade of treatment-related adverse events as assessed by CTCAE v4.03
Time frame: From predose to up to 5 days following the dosing and evaluation period