Study to Determine the Effect of BMS-791325 on the ECG QTcF Interval in Healthy Subjects

Hepatitis C Clinical Trial

Official title:

A Randomized, Double-Blinded, Positive-Controlled, Placebo-Controlled, 3-Way Crossover Study to Determine the Electrocardiographic Effects of BMS-791325 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02084953
• Other study ID #: AI443-112
• Status: Completed
• Phase: Phase 1
• First received: March 10, 2014
• Last updated: July 25, 2014
• Start date: April 2014
• Est. completion date: May 2014

Study information

• Verified date: July 2014
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether BMS-791325 has an effect on the electrocardiogram (ECG) interval QT corrected for Fridericia's method (QTcF).

Description:

Primary Purpose: Other: This Phase 1 study is a clinical pharmacology thorough QT study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 49 Years

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Healthy men and women, ages 18 to 49 yr old

• BMI 18 to 32

• Women must not be pregnant or breastfeeding

Exclusion Criteria:

• Any significant acute or chronic medical illness

• A personal history of clinically relevant cardiac disease, symptomatic or asymptomatic arrhythmias, presyncope or syncopal episodes, or additional risk factors for torsades de pointes (eg, heart failure)

• History of hypokalemia, personal history or family history of prolonged QT interval, or family history of sudden cardiac death at a young age

• History of biliary disorders, including Gilbert's disease or Dubin-Johnson disease

• Inability to swallow multiple tablets consecutively

• Any of the following on 12-lead electrocardiogram (ECG) prior to study drug administration: PR = 210 msec, QRS = 120 msec, QT = 500 msec, QTcF = 450 msec, Heart Rate (HR) < 45 bpm

• Second or third degree heart block prior to study drug

• Positive urine screen for drugs of abuse

• Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or Human Immunodeficiency Virus (HIV)-1, -2 antibody

• Any of the following lab results outside of the ranges specified below prior to dosing: Alanine aminotransferase (ALT) > upper limit of normal (ULN), Aspartate aminotransferase (AST) > ULN, Total bilirubin > ULN, Direct bilirubin > ULN, Creatinine > ULN, Serum potassium < lower limit of normal (LLN), Serum magnesium < LLN

• History of allergy to Moxifloxacin, BMS-791325, nonstructural protein 5B (NS5B) non-nucleoside inhibitors or related compounds

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Hepatitis C

Intervention

Drug:
• BMS-791325

• Moxifloxacin

• Placebo matching BMS-791325

Locations

Country	Name	City	State
United States	Ppd Development, Llc	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference from placebo of BMS-791325 in time-matched change from baseline (Day -1 on the study) to Day 3 of each period (??QTcF) at postdose extraction times for the QTcF		Approximately 28 days	Yes
Secondary	??HR, ??PR, ??QRS, ??QT	Difference from placebo in time-matched change from baseline (Day -1) to Day 3 at postdose extraction times in the ECG-derived RR or HR and other ECG intervals (PR, QRS, QT). QT is the unadjusted QT interval	Approximately 28 days	Yes
Secondary	Number and percent of subjects having a within-period maximum HR, PR, QRS, QT, QTcF, ?QT and ?QTcF within prespecified categories		Approximately 28 days	Yes
Secondary	Relationship between plasma concentrations of BMS-791325, BMS-794712, and BMS-948158, and the corresponding ??QTcF		Approximately 28 days	No
Secondary	Maximum observed concentration (Cmax) of BMS-791325, BMS-794712, and BMS-948158		43 timepoints up to day 26	No
Secondary	Time of maximum observed concentration (Tmax) of BMS-791325, BMS-794712, and BMS-948158		43 timepoints up to day 26	No
Secondary	Area under the concentration-time curve in one dosing interval (AUC(TAU)) of BMS-791325, BMS-794712, and BMS-948158		43 timepoints up to day 26	No
Secondary	Apparent total oral clearance (CLT/F) of BMS-791325, BMS-794712, and BMS-948158		43 timepoints up to day 26	No
Secondary	Terminal phase plasma half life (T-HALF) of BMS-791325, BMS-794712, and BMS-948158		43 timepoints up to day 26	No
Secondary	AUC(TAU) metabolic ratios of BMS-791325, BMS-794712, and BMS-948158		43 timepoints up to day 26	No
Secondary	Incidence of AEs, SAEs, AEs leading to discontinuation and death, marked laboratory abnormalities, findings on 12-lead safety ECG measurements and physical examination, and abnormalities in vital sign measurements exceeding pre-defined thresholds	Adverse event (AEs); Serious adverse event (SAEs)	Up to day 28	Yes
Secondary	Difference from placebo of Moxifloxacin in change from baseline (Day -1) to Day 3 at postdose extraction times for the QTcF (??QTcF)		Approximately 28 days	No

External Links

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