Evaluate the Effect of Orelabrutinib on Cardiac Repolarization in Healthy Subjects

NCT05660720 | Unknown Phase 1

• 1 other identifier: ICP-CL-00120
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Subject

Outcome Measures

Primary Outcomes (1)

• Placebo-corrected change-from-baseline QTcF interval

  Extraction of Holter ECGs from 1 h pre-dose to 24 h post-dose in each period.

  Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17

Secondary Outcomes (20)

• Change-from-baseline QTcF, PR, and QRS intervals

  Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17

• Change-from-baseline HR

  Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17

• Placebo-corrected change-from-baseline PR, and QRS intervals

  Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17

• Placebo-corrected change-from-baseline HR

  Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17

• Categorical outliers for QTcF, PR, and QRS

  Day1, Day2, Day6, Day7, Day11, Day12, Day16 and Day17

Study Arms (4)

Orelabrutinib tablet 150 mg (study drug) and placebo 250 mg (orelabrutinib tablet simulator)

EXPERIMENTAL

The subjects will be dosed once on Day1 or Day6 or Day11 or Day16 according to randomization.

Drug: Orelabrutinib and placebo (orelabrutinib tablet simulator)

Orelabrutinib 400 mg (study drug)

EXPERIMENTAL

The subjects will be dosed once on Day1 or Day6 or Day11 or Day16 according to randomization.

Drug: Orelabrutinib

Placebo 400mg (orelabrutinib tablet simulator)

PLACEBO COMPARATOR

The subjects will be dosed once on Day1 or Day6 or Day11 or Day16according to randomization.

Drug: Placebo (orelabrutinib tablet simulator)

Moxifloxacin hydrochloride 400 mg

ACTIVE COMPARATOR

he subjects will be dosed once on Day1 or Day6 or Day11 or Day16 according to randomization.

Drug: Moxifloxacin hydrochloride

Interventions

Orelabrutinib and placebo (orelabrutinib tablet simulator) DRUG

Orelabrutinib will be administered as 3 tablets (150mg) and placebo as 5 tablets (250mg)

Orelabrutinib tablet 150 mg (study drug) and placebo 250 mg (orelabrutinib tablet simulator)

Orelabrutinib DRUG

Orelabrutinib will be administered as 8 tablets (400mg)

Orelabrutinib 400 mg (study drug)

Placebo (orelabrutinib tablet simulator) DRUG

Placebo will be administered as 8 tablets (400mg).

Placebo 400mg (orelabrutinib tablet simulator)

Moxifloxacin hydrochloride DRUG

Moxifloxacin hydrochloride will be administered as 1 tablet (400mg)

Moxifloxacin hydrochloride 400 mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• After being informed and understanding of the trial process and possible adverse reactions of the drug, the subjects voluntarily signed an informed consent form (ICF) and confirmed their participation in all study procedures;
• Healthy subjects aged 18-45 years (inclusive) at the time of signing the informed consent;
• Weight of subjects ≥50.0 kg and ≤100.0 kg; Body mass index (BMI) ≥19.0 kg/m2 and ≤ 30.0 kg/m2, BMI= weight (kg)/height 2 (m2);
• Subjects do not have clinically meaningful medical history and various examinations including physical examination, vital signs, laboratory tests or ECG, and the results are normal or abnormal without clinical significance judged by investigators.
• Eligible fertile subjects (male and female) must agree to abstain from sex (avoid heterosexual sex) or use effective contraceptives with an annual contraceptive failure rate of less than 1% during the trial period until 3 months after the end of the trial.

You may not qualify if:

• History of any clinically serious disease like heart, liver, kidney, gastrointestinal tract, blood and respiratory system, immune system etc, with a history of fainting during acupuncture or injection or when seeing blood, or cannot tolerate venipuncture;
• Abnormal renal ,liver and pancreas function;
• Low blood pressure (systolic blood pressure\<90 mmHg; diastolic blood pressure\<60 mmHg) or hypertension (systolic blood pressure ≥ 140 mmHg; diastolic blood pressure ≥ 90 mmHg);
• Prolonged QTc interval that is at risk of causing torsade de pointes (TdP) requires drug treatment or other heart related abnormalities require drug treatment;
• The average value of three repetitions of 12 lead ECG at screening and before the first administration exceeded the standard: PR\>220 ms, QRS\>120 ms, HR\<50 bpm, QTcF\>450 ms (male and female), and any ECG abnormality with clinical significance determined by the investigator at screening;
• With a history of dysphagia or any gastrointestinal disease that affects drug absorption;
• With a history of drug or food allergy, or a history of specific allergies (asthma, urticaria, eczema, etc.); or allergic to moxifloxacin or other fluoroquinolones;
• Within 3 months before screening, those who have undergone surgery, have smoked more than 5 cigarettes or e-cigarettes daily, with a history of drug abuse or illicit drug use, or plan to undergo surgery during the study period, or with positive results of urine drug test at screening;
• Those who have used any prescription drugs, over-the-counter drugs, Chinese herbal medicines, or health products within 14 days before the first dose;
• People with positive results of one or more of the following tests: hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), HIV antigen/antibody joint test (HIV Ab), Treponema pallidum antibody (TP Ab) and COVID-19 at screening;
• Within 1 month before screening, those who have received anticoagulant therapy or thrombin inhibitor and/or antiplatelet therapy, any drug that inhibits or induces the metabolism of a drug by the liver;
• Those who have frequently used alcohol within 6 months before screening, or those who are unable to abstain from alcohol during the study period, or those who have positive results of breath alcohol test at the time of screening;
• Within 7 days before screening those who have drunk excessive tea, coffee or caffeinated beverages, or who have eaten fruits or food that affect metabolic enzymes, within 1 months before screening who are used to beverages or food rich in xanthine ingredients, and those who are unable to abstain from such beverages, fruits or food mentioned above during the whole study period;
• Those who have participated in 4 or more clinical trials during the past one year; who have taken other study drugs or participated in other drug clinical trials within 3 months before screening;
• Those who have donated blood or plan to donate blood within 3 months before screening, or have received blood transfusion within 4 weeks before screening;

Sponsors & Collaborators

• Beijing InnoCare Pharma Tech Co., Ltd.: lead

Study Sites (1)

Beijing GoBroad Boren Hospital

Beijing, China

Location

MeSH Terms

Interventions

orelabrutinib; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2022
• First Posted: December 21, 2022
• Study Start: November 19, 2022
• Primary Completion: June 30, 2023
• Study Completion: August 31, 2023
• Last Updated: December 21, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)