Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

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

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: 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.

Relevance to patient case: not relevant