This Phase I/II clinical trial is designed to evaluate, through a single-dose Phase I segment and a multiple-dose Phase II segment, the safety/tolerability, pharmacokinetic (PK) profile, and pharmacodynamic (PD) characteristics of BEBT-701 administered by subcutaneous injection in patients with mild to moderate hypertension and elevated LDL-C , and to explore its preliminary efficacy.
This study employs an integrated Phase I/II seamless adaptive design. Stage 1 is a single-dose Phase I component, randomized, double-blind, and placebo-controlled, with five pre-specified dose cohorts starting at 100 mg. Its primary objectives are to characterize the safety, tolerability, PK, PD, and preliminary efficacy of single-dose BEBT-701 across the planned dose range, thereby providing critical input for dose and dosing-interval selection for Stage 2. After a 2- to 4-week observation period following the last Phase I cohort, three doses (preliminary) will be selected from the accumulated data to initiate Stage 2, a multiple-dose Phase II segment. This stage is a randomized, double-blind, parallel-group comparison of three active dose levels versus placebo. Placebo recipients will crossover to active treatment at Week 12 after the second dose; active-arm subjects will enter a double-blind extension after completing the 24-week post-second-dose visit, enabling collection of longer-term safety and efficacy data.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
340
Phase I: The starting dose of BEBT-701 injection is 100 mg; the single subcutaneous doses are 100 mg, 200 mg, 400 mg, 800 mg, and 1200 mg. Phase II: Based on the preliminary Phase I findings, three dose levels will be selected for the Phase II study, with BEBT-701 injection administered subcutaneously on Day 1 and Day 85.
Phase I:BEBT-701 injection placebo, administered as a single subcutaneous dose. Phase II:BEBT-701 injection placebo administered subcutaneously on Day 1 and Day 85.
The Third Xiangya Hospital of Central South University
Changsha, Hunan, China
Occurrence of Adverse Events (AEs)
Occurrence of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE V5.0).
Time frame: Up to 36 months
Low-Density Lipoprotein Cholesterol(LDL-C)
Percentage change from baseline in LDL-C after dosing.
Time frame: Up to 24 weeks
24hour-Ambulatory Blood Pressure Monitoring(24h-ABPM)
Change from baseline in mean 24h-ABPM systolic blood pressure (SBP) after dosing.
Time frame: Up to 24weeks
AUC0-∞
The area under the plasma concentration-time curve from time zero to infinity.
Time frame: Phase I:From pre-dose to 72 h post-dose on Day 1; Phase II:From pre-dose to 72 h post-dose on Day 1and Day 85.
Cmax
The maximum plasma drug concentration
Time frame: Phase I:From pre-dose to 72 h post-dose on Day 1; Phase II:From pre-dose to 72 h post-dose on Day 1and Day 85.
Tmax
The time to reach maximum plasma drug concentration
Time frame: Phase I:From pre-dose to 72 h post-dose on Day 1; Phase II:From pre-dose to 72 h post-dose on Day 1and Day 85.
t1/2
The time for plasma drug concentration to halve
Time frame: Phase I:From pre-dose to 72 h post-dose on Day 1; Phase II:From pre-dose to 72 h post-dose on Day 1and Day 85.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Blood pressure-related parameters
Percentage change from baseline in mean 24-h ABPM SBP; Change from baseline in mean 24-h ABPM SBP; Change from baseline and percentage change from baseline in mean 24-h ABPM DBP,standard daytime mean SBP and DBP (6 a.m.-10 p.m.), standard nighttime mean SBP and DBP (10 p.m.-6 a.m.); Change from baseline and percentage change from baseline in office seated SBP, DBP, and mean arterial pressure (MAP).
Time frame: Up to 24 weeks
Lipid-related parameters
Percentage change from baseline in LDL-C;Change from baseline and percentage change from baseline in total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), non-high-density-lipoprotein cholesterol (non-HDL-C), very-low-density-lipoprotein cholesterol (VLDL-C), apolipoprotein B, apolipoprotein A1, triglycerides, and lipoprotein(a).
Time frame: Up to 24 weeks
Angiotensinogen(AGT)
Change from baseline and percentage change from baseline in AGT.
Time frame: Up to 36 weeks
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
Change from baseline and percentage change from baseline in PCSK9.
Time frame: Up to 36 weeks