Evaluate the Effect of Orelabrutinib on Cardiac Repolarization in Healthy Subjects
- Conditions
- Healthy Subject
- Interventions
- Drug: Placebo (orelabrutinib tablet simulator)
- Registration Number
- NCT05660720
- Lead Sponsor
- Beijing InnoCare Pharma Tech Co., Ltd.
- Brief Summary
This is A Randomized, Blinded, Placebo- and Positive-Controlled, Four-Period, Crossover-Design Thorough QT/QTc (TQT) Study to Evaluate the Effect of Orelabrutinib on Cardiac Repolarization in Healthy Subjects
- Detailed Description
This is a randomized, blinded, placebo- and positive-controlled, four-period, crossover clinical study. A double-blind design is used for administration of orelabrutinib tablet and placebo, and an open-label design is used for moxifloxacin hydrochloride tablet.Subjects who meet all inclusion criteria and do not meet any of the exclusion criteria are randomly assigned to one of 12 treatment sequences, and each treatment sequence includes 4 periods, with a 5-day washout period between treatment periods. The subject will complete all the visit examinations on Day 17 after the first dose, then will be discharged from the study site, and will receive telephone follow-up on Day 8 ± 2 after the last dose date. If a subject has clinically significant abnormal examination results when discharging from the study site after the last dose, on-site follow-up is essential to track the abnormal examination results, or otherwise, only telephone follow-up is required.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 48
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Orelabrutinib 400 mg (study drug) Orelabrutinib The subjects will be dosed once on Day1 or Day6 or Day11 or Day16 according to randomization. Moxifloxacin hydrochloride 400 mg Moxifloxacin hydrochloride he subjects will be dosed once on Day1 or Day6 or Day11 or Day16 according to randomization. Orelabrutinib tablet 150 mg (study drug) and placebo 250 mg (orelabrutinib tablet simulator) Orelabrutinib and placebo (orelabrutinib tablet simulator) The subjects will be dosed once on Day1 or Day6 or Day11 or Day16 according to randomization. Placebo 400mg (orelabrutinib tablet simulator) Placebo (orelabrutinib tablet simulator) The subjects will be dosed once on Day1 or Day6 or Day11 or Day16according to randomization.
- Primary Outcome Measures
Name Time Method Placebo-corrected change-from-baseline QTcF interval Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Extraction of Holter ECGs from 1 h pre-dose to 24 h post-dose in each period.
- Secondary Outcome Measures
Name Time Method Change-from-baseline QTcF, PR, and QRS intervals Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Extraction of Holter ECGs from 1 h pre-dose to 24 h post-dose in each period.
Change-from-baseline HR Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Extraction of Holter ECGs from 1 h pre-dose to 24 h post-dose in each period.
Placebo-corrected change-from-baseline PR, and QRS intervals Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Extraction of Holter ECGs from 1 h pre-dose to 24 h post-dose in each period.
Placebo-corrected change-from-baseline HR Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Extraction of Holter ECGs from 1 h pre-dose to 24 h post-dose in each period.
Categorical outliers for QTcF, PR, and QRS Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Extraction of Holter ECGs from 1 h pre-dose to 24 h post-dose in each period.
Categorical outliers for HR Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Extraction of Holter ECGs from 1 h pre-dose to 24 h post-dose in each period.
Frequency of treatment-emergent changes of T-wave morphology and U-waves presence Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Extraction of Holter ECGs from 1 h pre-dose to 24 h post-dose in each period.
Tmax of Orelabrutinib after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
Cmax of Orelabrutinib after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
AUC of Orelabrutinib after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
T1/2 of Orelabrutinib after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
CL/F of Orelabrutinib after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
Vz/F of Orelabrutinib after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
Tmax of moxifloxacin after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
Cmax of moxifloxacin after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
AUC of moxifloxacin after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
T1/2 of moxifloxacin after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
CL/F of moxifloxacin after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
Vz/F of moxifloxacin after single dose Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17 Plasma samples will be collected from all the subjects for PK analysis. For each period, venous blood will be collected within 30 min pre-dose, and 0.5 h, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, and 24.0 h post-dose.
Serious adverse events (SAEs) occurring from administration of drugst to follow-up period or early withdrawal, incidence of treatment-emergent adverse events Through study completion, an average of 1 year SAE and TEAE
Trial Locations
- Locations (1)
Beijing GoBroad Boren Hospital
🇨🇳Beijing, China