The Effect of Hydrocodone Bitartrate (HYD) Extended-Release Tablets on QT /QTc Intervals in Healthy Adult Subjects

Sponsor

Purdue Pharma LP (Industry)

Overall Status

Completed

CT.gov ID

NCT02243241

Collaborator

(none)

208

Enrollment

Location

Arms

5.9

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Evaluate the effect of multiple doses (once daily for 3 days each of HYD 80, 120, and 160 mg tablets) on the QT/QTc interval.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: HYD Drug: Moxifloxacin Drug: Placebo for HYD Drug: Placebo for moxifloxacin	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

208 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Official Title:

A Randomized, Double-blind, Placebo- and Positive-Controlled, Parallel Group, Dose Escalating Study of the Effect of Hydrocodone Bitartrate (HYD) Extended-Release Tablets at Doses up to 160 mg on QT/QTc in Healthy Adult Subjects

Study Start Date :

Nov 1, 2012

Actual Primary Completion Date :

May 1, 2013

Actual Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HYD	Drug: HYD Hydrocodone bitartrate 80 mg (day 9), 120 mg (day 12), 160 mg [(1) 40 mg tablet + (1) 120 mg tablet] (day 15) extended-release tablets administered orally every 24 hours. Drug: Placebo for moxifloxacin Placebo to match moxifloxacin tablets administered orally on the mornings of day 9, day 12, and day 15 only.
Other: Moxifloxacin Moxifloxacin is the positive control.	Drug: Moxifloxacin Moxifloxacin 400 mg tablets administered orally on the morning of day 9, day 12, and day 15 only. Other Names: Avelox® Drug: Placebo for HYD Placebo to match HYD tablets administered orally every 24 hours.
Placebo Comparator: Placebo Placebo for HYD and placebo for moxifloxacin	Drug: Placebo for HYD Placebo to match HYD tablets administered orally every 24 hours. Drug: Placebo for moxifloxacin Placebo to match moxifloxacin tablets administered orally on the mornings of day 9, day 12, and day 15 only.

Arm

Intervention/Treatment

Experimental: HYD

Drug: HYD

Hydrocodone bitartrate 80 mg (day 9), 120 mg (day 12), 160 mg [(1) 40 mg tablet + (1) 120 mg tablet] (day 15) extended-release tablets administered orally every 24 hours.

Drug: Placebo for moxifloxacin

Placebo to match moxifloxacin tablets administered orally on the mornings of day 9, day 12, and day 15 only.

Other: Moxifloxacin

Moxifloxacin is the positive control.

Drug: Moxifloxacin

Moxifloxacin 400 mg tablets administered orally on the morning of day 9, day 12, and day 15 only.

Other Names:

Avelox®

Drug: Placebo for HYD

Placebo to match HYD tablets administered orally every 24 hours.

Placebo Comparator: Placebo

Placebo for HYD and placebo for moxifloxacin

Drug: Placebo for HYD

Placebo to match HYD tablets administered orally every 24 hours.

Drug: Placebo for moxifloxacin

Placebo to match moxifloxacin tablets administered orally on the mornings of day 9, day 12, and day 15 only.

Outcome Measures

Primary Outcome Measures

The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method [Baseline and Day 9]
The electrocardiogram (ECG) effects of HYD 80 mg (day 9) on the QT/QTc interval
The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method [Baseline and Day 12]
The ECG effects of HYD 120 mg (day 12) on the QT/QTc interval
The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method [Baseline and Day 15]
The ECG effects of HYD 160 mg (day 15) on the QT/QTc interval

Secondary Outcome Measures

The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method [Baseline and Day 9]
The ECG effects of moxifloxacin (day 9) on the QT/QTc interval
The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method [Baseline and Day 12]
The ECG effects of moxifloxacin (day 12) on the QT/QTc interval
The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method [Baseline and Day 15]
The ECG effects of moxifloxacin (day 15) on the QT/QTc interval

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Provide written informed consent;
Body weight ranging from 50 to 100 kilograms (kg) [110 to 220 pounds] and body mass index (BMI) of 18 to 30 (kg/m2);
Males and females aged 18 to 50 years;
Willing to eat the food supplied during the study;
Willing to refrain from strenuous exercise through the end-of-study visit. Subjects did not begin a new exercise program nor participate in any unusually strenuous physical exertion;
Healthy and free of significant abnormal findings as determined by medical history, physical examination, clinical laboratory values, vital signs, and safety 12-lead ECG;
Females of childbearing potential must use an adequate and reliable method of contraception (ie, barrier with additional spermicidal foam or jelly, intra-uterine device, hormonal contraception). Females who are postmenopausal must be postmenopausal for ≥ 1 year and have elevated serum follicle stimulating hormone (FSH).

Exclusion Criteria:

Females who are pregnant (positive beta human chorionic gonadotropin test) or lactating;
Current or recent (within 5 years) history of drug or alcohol abuse;
History or any current conditions that may interfere with drug absorption, distribution, metabolism, or excretion;
Use of an opioid-containing medication in the past 30 days preceding the initial dose in this study;
Known allergy to hydrocodone, opioids, psychotropic or hypnotic drugs, moxifloxacin, or any member of the quinolone class drugs;
Any history of frequent nausea or emesis regardless of etiology;
Any history of seizures or head trauma with sequelae;
Participation in a clinical drug study during the 30 days preceding the initial dose of study drug in this study;
Use of any medication including thyroid hormonal therapy (hormonal contraception and hormonal replacement therapy in the form of estrogen with or without progestin is allowed), vitamins, herbal and/or mineral supplements during the 7 days preceding the initial dose of study drug;
Any significant illness during the 30 days preceding the initial dose of study drug in this study;
Any personal or family history of prolonged QT interval or disorders of cardiac rhythm;
Abnormal cardiac conditions including hypertension;
Abnormal cardiac condition denoted by any of the following:
QT data corrected for heart rate using the Fridericia formula (QTcF) interval

450 milliseconds (msec)

PR interval >240 msec or QRS >110 msec
Evidence of second- or third-degree atrioventricular block
Pathological Q-waves (defined as Q-wave >40 msec or depth >0.5 millivolts [mV])
Evidence of ventricular pre-excitation, complete left bundle branch block (LBBB), right bundle branch block (RBBB), or incomplete RBBB
With a resting heart rate (HR) outside the range of 40 to 90 beats per minute (bpm);
Abnormalities on physical examination, vital signs, safety 12-lead ECG, or clinical laboratory values, unless those abnormalities are judged clinically insignificant by the investigator;
Oxygen saturation <94% as measured by pulse oximetry (SpO2);
Refusal to abstain completely from caffeine or xanthine during confinement;
Refusal to abstain from consumption of alcoholic beverages 48 hours prior to initial study drug administration through the end-of-study visit;
Blood or blood products donated within 30 days prior to initial study drug administration or any time through the end-of-study visit, except as required by the study protocol;
History of smoking or use of nicotine products within 45 days of initial study drug administration or a positive urine cotinine test;
Positive results of urine drug screen or alcohol screen;
Positive results of hepatitis B surface antigen (HBsAg), hepatitis C antibody (anti-HCV);
Presence of Gilbert's Syndrome or any known hepatobiliary abnormalities;
The investigator believes the subject to be unsuitable for reason(s) not specifically stated in the exclusion criteria.