Clinical Study to Evaluate Effect on QT/QTc Interval After Multiple Dose of Celecoxib

A Randomized, Open-label, Negative and Positive Control, Crossover Clinical Study to Evaluate Effect on QT/QTc Interval After Multiple Dose of Celecoxib in Healthy Adult Volunteers

This study is conducted to evaluate effect on QT/QTc Interval after multiple dose of celecoxib among healthy adult volunteers. It is randomized, open-label, negative and postive control, and crossover study. Volunteers will be mainly checked up through ECG to find out changes of QT/QTc interval during the study.

Study Overview

• Status: Completed
• Conditions: Qt Interval, Variation in
• Intervention / Treatment: Drug: Celecoxib; Drug: Moxifloxacin; Other: Water

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adults between 19-year-old and 40-year-old during the screening day
• BMI between 19 kg/m² and 30 kg/m² during the screening day
• Be able to give an informed consent form after understanding for reasonable explanation of clinical trial's purpose, contents and characteristics of clinical drugs
• Wiling to participate whole clinical trial periods

Exclusion Criteria:

• Person who is able to clinically affect to the study through ECG result during the screening day
• Has critical issue for Torsade de points from heart failure, hypopotassemia, arrhythmia etc., or family history for long QT syndrome, sudden cardiac death.
• Was suffered, or is suffering from like liver, kidney, digestive system, circulatory system, respiratory system, endocrine system(except diabetes), musculoskeletal, neuropsychiatry, or hemato-oncology etc., which is able to effect on clinical study
• Has allergy which is required the treatment or hypersensitive from drugs such as aspirin, anti-biotics, anti-depressants, etc.
• Was administered any drug of other clinical study within 90 days from the randomization day.
• Donated whole blood within 60days or apheresis within 30 days from the randomization day.
• Took any medicine or oriental medicine within 2 weeks, or general pharmaceuticals within 7 days from the randomization day. (For general pharmaceuticals circumstances, PI could decide whether he/she is suitable for the study)
• No intention to take contraceptive which is approved as clinical way, or is planning on giving their sperm or egg during the whole clinical trial.
• Average alcohol consumption per week: >140g
• Average smoking per day: >20
• Average grapefruit juice consumption per day: >4 glasses
• systolic blood pressure <100 mmHg or >150 mmHg, or diastolic pressure <70 mmHg or >100mmHg
• Over 2 times from the maximum reference interval of AST and ALT levels in the blood.
• eGFR by MDRD from creatinine in the blood is less than 30 mL/min.
• doesn't show negative reaction from HIV Test, B hepatitis test, or C hepatitis test
• For woman, doesn't show negative reaction from pregnancy test
• PI decides the person is not suitable to participate the clinical study with other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Celecoxib, Moxifloxacin, Water in order; Intervention Celecoxib: Celecoxib 400 mg capsule and water 150ml by mouth, daily for 6daysWash-out period (3~6 days); Intervention Moxifloxacin: Moxifloxacin 400 mg tablet and water 150ml by mouth, once for one dayWash-out period (3~6 days); Intervention Pure water: Water 150ml by mouth without any drug, once for one day	Drug: Celecoxib; Celecoxib 400mg capsule; Other Names: Celebrex; Drug: Moxifloxacin; Moxifloxacin 400mg tablet; Other Names: Avelox; Other: Water; Pure water 150ml
Experimental: Celecoxib, Water, Moxifloxacin in order; Intervention Celecoxib: Celecoxib 400 mg capsule and water 150ml by mouth, daily for 6daysWash-out period (3~6 days); Intervention Pure water: Water 150ml by mouth without any drug, once for one dayWash-out period (3~6 days); Intervention Moxifloxacin: Moxifloxacin 400 mg tablet and water 150ml by mouth, once for one day	Drug: Celecoxib; Celecoxib 400mg capsule; Other Names: Celebrex; Drug: Moxifloxacin; Moxifloxacin 400mg tablet; Other Names: Avelox; Other: Water; Pure water 150ml
Experimental: Moxifloxacin, Water, Celecoxib in order; Intervention Moxifloxacin: Moxifloxacin 400 mg tablet and water 150ml by mouth, once for one dayWash-out period (3~6 days); Intervention Pure water: Water 150ml by mouth without any drug, once for one dayWash-out period (3~6 days); Intervention Celecoxib: Celecoxib 400 mg capsule and water 150ml by mouth, daily for 6days	Drug: Celecoxib; Celecoxib 400mg capsule; Other Names: Celebrex; Drug: Moxifloxacin; Moxifloxacin 400mg tablet; Other Names: Avelox; Other: Water; Pure water 150ml
Experimental: Water, Moxifloxacin, Celecoxib in order; Intervention Pure water: Water 150ml by mouth without any drug, once for one dayWash-out period (3~6 days); Intervention Moxifloxacin: Moxifloxacin 400 mg tablet and water 150ml by mouth, once for one dayWash-out period (3~6 days); Intervention Celecoxib: Celecoxib 400 mg capsule and water 150ml by mouth, daily for 6days	Drug: Celecoxib; Celecoxib 400mg capsule; Other Names: Celebrex; Drug: Moxifloxacin; Moxifloxacin 400mg tablet; Other Names: Avelox; Other: Water; Pure water 150ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in QTc interval, read manually	which is analyzed at the date of initial and final administration of celecoxib, moxifloxacin, water toward healthy volunteers.	-1 hour, -40 minutes, -20 minutes pre-dose at initial administration day and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at last administration day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in QTc , measured automatically	which is analyzed at the date of initial and final administration of celecoxib, moxifloxacin, water toward healthy volunteers.	-1 hour, -40 minutes, -20 minutes pre-dose at initial administration day and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at last administration day
ventricular rate, measured automatically	which is analyzed at the date of initial and final administration of celecoxib, moxifloxacin, water toward healthy volunteers.	-1 hour, -40 minutes, -20 minutes pre-dose at initial administration day and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at last administration day
PR duration, measured automatically	which is analyzed at the date of initial and final administration of celecoxib, moxifloxacin, water toward healthy volunteers.	-1 hour, -40 minutes, -20 minutes pre-dose at initial administration day and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at last administration day
RR duration, measured automatically	which is analyzed at the date of initial and final administration of celecoxib, moxifloxacin, water toward healthy volunteers.	-1 hour, -40 minutes, -20 minutes pre-dose at initial administration day and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at last administration day
QRS duration, measured automatically	which is analyzed at the date of initial and final administration of celecoxib, moxifloxacin, water toward healthy volunteers.	-1 hour, -40 minutes, -20 minutes pre-dose at initial administration day and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at last administration day
Area under the curve within a dosing interval at steady state	which is analyzed at the date of final administration of celecoxib	0 hour pre-dose and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at final administration day(Day6)
Maximum concentration at steady state	which is analyzed at the date of final administration of celecoxib	0 hour pre-dose and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at final administration day(Day6)
Time to maximum concentration at steady state	which is analyzed at the date of final administration of celecoxib	0 hour pre-dose and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at final administration day(Day6)
Minimum concentration at steady state	which is analyzed at the date of final administration of celecoxib	0 hour pre-dose and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at final administration day(Day6)
Area under the concentration-time curve time zero to the time of the last quantifiable concentration	which is analyzed at the date of final administration of moxifloxacin	0 hour pre-dose and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at final administration day(Day1)
Maximum concentration	which is analyzed at the date of final administration of moxifloxacin	0 hour pre-dose and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at final administration day(Day1)
Time to maximum concentration	which is analyzed at the date of final administration of moxifloxacin	0 hour pre-dose and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at final administration day(Day1)
Half-life	which is analyzed at the date of final administration of moxifloxacin	0 hour pre-dose and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at final administration day(Day1)
The apparent clearance	which is analyzed at the date of final administration of moxifloxacin	0 hour pre-dose and 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post-dose at final administration day(Day1)

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: JUNGRYUL KIM, MD, PhD, Samsung Medical Center

Publications and helpful links

General Publications

• Kim S, Lee H, Ko JW, Kim JR. Effects of Celecoxib on the QTc Interval: A Thorough QT/QTc Study. Clin Ther. 2019 Nov;41(11):2204-2218. doi: 10.1016/j.clinthera.2019.09.004. Epub 2019 Sep 26.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2017
• Primary Completion (Actual): May 25, 2018
• Study Completion (Actual): May 25, 2018

Study Registration Dates

• First Submitted: November 8, 2018
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 29, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cyclooxygenase 2 Inhibitors; Moxifloxacin; Celecoxib
• Other Study ID Numbers: 2016-11-053

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No