Clinical trial NCT02243241: The Effect of Hydrocodone Bitartrate (HYD) Extended-Release Tablets on QT /QTc Intervals in Healthy Adult Subjects
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy volunteers
Opioid
ECG
QTcI
Lead sponsor: Purdue Pharma LP
Sponsor class: INDUSTRY
First posted: 2014-09-17
Enrollment: 208
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
timeFrame: Baseline and Day 9
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
timeFrame: Baseline and Day 12
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
timeFrame: Baseline and Day 15
Secondary outcomes:
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
timeFrame: Baseline and Day 9
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
timeFrame: Baseline and Day 12
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
timeFrame: Baseline and Day 15
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD Phase I Clinic
state: Texas
Study officials:
References: