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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: HYD; Drug: Moxifloxacin; Drug: Placebo for moxifloxacin; Drug: Placebo for HYD

• Registration Number: NCT02243241
• Lead Sponsor: Purdue Pharma LP

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-11
• Primary Completion: 2013-05
• Study Completion: 2013-05
• Status Verified: 2014-09
• Study First Submitted: 2014-09-15
• Study First Submitted QC: 2014-09-15
• Last Update Submitted: 2014-09-15
• Study First Posted: 2014-09-17
• Last Update Posted: 2014-09-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 208

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo for moxifloxacin	Placebo for HYD and placebo for moxifloxacin
HYD	Placebo for moxifloxacin	-
Moxifloxacin	Placebo for HYD	Moxifloxacin is the positive control.
HYD	HYD	-
Moxifloxacin	Moxifloxacin	Moxifloxacin is the positive control.
Placebo	Placebo for HYD	Placebo for HYD and placebo for moxifloxacin

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

PPD Phase I Clinic; 🇺🇸 Austin, Texas, United States