Race Difference Moxifloxacin-induced QT Prolongation Between Healthy Chinese and Caucasian Volunteers

Cardiac Toxicity Clinical Trial

Official title:

A Double-center, Randomized, Double-blinded, 2-way Crossover, Placebo-controlled Study: Comparison of Single Oral Dose 400mg Moxifloxacin-induced QT Prolongation Between Healthy Chinese Volunteers and Caucasian Volunteers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02119091
• Other study ID #: PUTH_CTC_2013_001
• Status: Recruiting
• Phase: Phase 1
• First received: April 15, 2014
• Last updated: April 17, 2014
• Start date: April 2014
• Est. completion date: December 2014

Study information

• Verified date: April 2014
• Source: Peking University Third Hospital
• Contact: Jingchuan Guo, MD
• Phone: +86-13811161216
• Email: guojingchuan1029[@]126.com
• Is FDA regulated: No
• Health authority: China: Food and Drug AdministrationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

A double-center, randomized, double-blinded, 2-way crossover, placebo-controlled Study: Comparison of single oral dose 400mg Moxifloxacin-induced QT prolongation between healthy Chinese volunteers and Caucasian Volunteers Study Objective:Primary Objective:To compare the difference of ΔΔQTcF (Baseline-adjusted, placebo-corrected effect on QTcF) between Chinese group and Caucasian group under the same exposure (Cmax) of Moxifloxacin.Secondary Objectives:1)To compare the difference of ΔΔQTcF, heart rate, PR, RR, QRS and Moxifloxacin plasma concentration between Chinese group and Caucasian group.2)To compare slopes of Moxifloxacin plasma Concentration/QTcF value between healthy Chinese volunteers and Caucasian Volunteers.

Description:

A total 80 healthy subjects will be enrolled in both sites, both male and female, age 18-45 years old. Half of them will be healthy Chinese volunteers, both male and female; will be recruited to obtain at least 36 evaluable volunteers in Chinese site of CTC, PUTH. The other half will be healthy Caucasian volunteers, both male and female; will be recruited to obtain at least 36 evaluable volunteers in the U.S. site of Spaulding Clinical Research LLC. An evaluable subject is defined as a volunteer completing all study procedures from the screening period to the final ECG nominal time-point for QTc interval measurement and final blood sampling for plasma levels of Moxifloxacin on the last study day (Day 2 of the second period).

Study Objective:Primary Objective:To compare the difference of ΔΔQTcF (Baseline-adjusted, placebo-corrected effect on QTcF) between Chinese group and Caucasian group under the same exposure (Cmax) of Moxifloxacin.Secondary Objectives:1)To compare the difference of ΔΔQTcF, heart rate, PR, RR, QRS and Moxifloxacin plasma concentration between Chinese group and Caucasian group.2)To compare slopes of Moxifloxacin plasma Concentration/QTcF value between healthy Chinese volunteers and Caucasian Volunteers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Healthy Chinese subjects, male and female, 18 to 45 years of age, inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.(only for PUTH site) Or, healthy non-Hispanic Caucasian subjects, male and female, 18 to 45 years of age, inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening (only for SCR site).

2. At Screening and baseline day, vital signs (systolic and diastolic blood pressure and heart rate rate) will be assessed in the sitting position after the subject has rested for 5 minutes. All of vital signs should be within normal ranges:

• Body temperature (Oral) between 35.0-37.0°C

• 90 mm Hg = systolic blood pressure <150 mm Hg

• 50 mm Hg= diastolic blood pressure < 90 mm Hg

• 50beats per minute= Heart rate = 90 beats per minute

3. Body weight need to be at least 50kg or above, 18Kg/m2= Body Mass Index(BMI) =31Kg/m2

4. Be able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent forms prior to any screening procedures.

Exclusion Criteria:

1. Subject has a 12 lead ECG result at Screening or Check in with evidence of any of the following abnormalities after the subject has rested for approximately10 minutes.

• QTcF>450 ms for males and females

• PR interval >240 ms or <110 ms

• Second-degree or third-degree atrioventricular block(AVB)

• Complete left or right bundle branch block or incomplete left bundle branch block

• QRS duration >120 ms

• Heart rate <50 beats per minute or >90 beats per minute

• Pathological Q-waves (defined as Q-wave =40 ms)

• Ventricular pre-excitation

2. Subject has a history of unexplained syncope, structural heart disease, long QT syndrome, heart failure, myocardial infarction, angina, unexplained cardiac arrhythmia, torsades de points, or ventricular tachycardia. Subjects will also be excluded if there is a family history of long QT syndrome (genetically proven or suggested by sudden death of a close relative due to cardiac causes at a young age) or Brugada syndrome.

3. Subject has hypokalemia, hypocalcemia, or hypomagnesemia according to lower limits of the reference ranges provided by the clinical laboratory.

4. Subject has a history or current evidence of anaphylactic reactions or clinically significant (as determined by the investigator) allergic conditions (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

5. Subject has a hypersensitivity or allergy to moxifloxacin or any drug in the fluoroquinolone class (eg, ciprofloxacin or levofloxacin).

6. History or clinical manifestations of significant metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, genetic or psychiatric disorders.

7. Current or recent history (< 30 days prior to Screening) of a clinically significant illness.

8. Use of any prescription drugs, herbal supplements, within 4 weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within 4 week prior to initial dosing.

9. Positive results of human immunodeficiency virus, Hepatitis B surface antigen or Hepatitis C antibody testing.

10. Current use of tobacco (> 10 tobacco/day) or nicotine-containing products. .

11. History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening and/or at baseline.

12. Dosing of study drug in any clinical investigation within 30 days prior to initial dosing.

13. Donation or loss of 200 ml or more of blood within 30 days prior to participation, or donation of component blood within 30 days prior to participation.

14. Consumption of alcohol-, caffeine -containing foods or beverages within 48 hours preceding study drug administration.

15. Females are currently pregnant, breast-feeding or planning a pregnancy in the next 3 months.

16. Other conditions which investigator deems potential harm to subjects if participate the study.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiac Toxicity
• Long QT Syndrome

Intervention

Drug:
• Moxifloxacin

Locations

Country	Name	City	State
China	Peking University Third Hospital Clinical Trial Center	Beijing	Beijing
United States	Spaulding Clinical Research LLC	West Bend	Wisconsin

Sponsors (5)

Lead Sponsor	Collaborator
Haiyan Li	BioClinica, Inc., Food and Drug Administration (FDA), Peking University, Spaulding Clinical Research LLC

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	??QTcF	To compare the difference of ??QTcF (Baseline-adjusted, placebo-corrected effect on QTcF) between Chinese group and Caucasian group under the same exposure (Cmax) of Moxifloxacin	2 months	Yes