The Effect of Buprenorphine Delivered by Buprenorphine Transdermal System (BTDS) at Doses up to 80 Micrograms/Hour (mcg/hr) and Naltrexone on Electrocardiogram (ECG) Intervals in Healthy Volunteers
Condition: ECG Effects
Intervention: Buprenorphine transdermal patch; Naltrexone tablet; Placebos (for TDS and for naltrexone and for moxifloxacin); Moxifloxacin tablet
Intervention description: Buprenorphine patch applied transdermally; Naltrexone tablet; 1 tablet taken orally every 12 hours; Matching placebos; Moxifloxacin tablet; 1 tablet taken orally on Days 6, 13 and 17
Intervention MeSH terms: Moxifloxacin; Naltrexone; Buprenorphine; Norgestimate, ethinyl estradiol drug combination
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 328.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy subjects; Opioid; Transdermal; ECG

Summary:

      The purpose of this study is to evaluate the ECG effects of 10, 40, and 80 mcg/hr
      buprenorphine delivered by BTDS alone, or by BTDS dosed with naltrexone, relative to placebo
      in healthy male and female subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provide written informed consent.

          -  Males and females aged 18 to 55, inclusive.

          -  Body weight ranging from 50 to 100 kilograms (kg) (110 to 220 lbs) and body mass index
             (BMI) ranging from 18 to 30 (kg/m2), inclusive.

          -  Healthy and free of significant abnormal findings as determined by medical history,
             physical examination, clinical laboratory values, vital signs, and resting 12-lead
             ECG.

          -  Females of child-bearing potential must be using 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 have been
             postmenopausal ≥ 1 year and have elevated serum follicle stimulating hormone (FSH).

          -  Willing to eat the food supplied during the study.

          -  Willing to refrain from strenuous exercise during the entire study. Subjects will not
             begin a new exercise program nor participate in any unusually strenuous physical
             exertion.

          -  All 8 anatomical transdermal system (TDS) application sites (upper back, upper chest,
             upper outer arm, or lateral thorax) must be acceptable for study use.

        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 might interfere with drug absorption
             (transdermal or gastrointestinal), 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 buprenorphine, any excipient of BTDS, opioids, psychotropic or
             hypnotic drugs, and/or 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
             in this study.

          -  Any significant illness during the 30 days preceding the initial dose 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.

          -  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:

               -  QTcF interval > 450 milliseconds (msec)

               -  PR interval > 240 msec or QRS > 110 msec

               -  Evidence of second- or third-degree atrioventricular (AV) block

               -  Pathological Q-waves (defined as Q-wave >40 msec or depth > 0.5 mV)

               -  Evidence of ventricular pre-excitation, complete left bundle branch block, right
                  bundle branch block (RBBB), or incomplete RBBB

               -  With a resting heart rate outside the range of 45 to 85 beats per minute (bpm)

          -  Abnormalities on physical examination, vital signs, ECG, or clinical laboratory
             values, unless those abnormalities were judged clinically insignificant by the
             investigator.

          -  Oxygen saturation (SpO2) ≤ 94% as measured by pulse oximetry.

          -  Refusal to abstain from caffeine or xanthine containing beverages entirely during
             confinement.

          -  Refusal to abstain from consumption of alcoholic beverages 48 hours prior to initial
             study drug administration and any time during study.

          -  History of smoking or use of nicotine products within 45 days of study drug
             administration or a positive urine cotinine test

          -  Blood or blood products donated within 30 days prior to study drug administration or
             anytime during the study.

          -  Positive results of urine drug screen or alcohol screen.

          -  Positive results of hepatitis B surface antigen (HBsAg), hepatitis C antibody
             (anti-HCV).

          -  Positive naloxone challenge test.

          -  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.

          -  Subjects who have allergies or other contraindications to transdermal systems or patch
             adhesives.

          -  Clinically significant history of allergic reaction to wound dressings or elastoplast.

          -  Subjects with a dermatological disorder at any relevant patch application site that
             precludes proper placement and/or rotation of patch.

          -  Taking antihistamines within 72 hours prior to dosing or systemic or topical
             corticosteroids within 3 weeks prior to dosing.

          -  Subjects will not allow hair to be removed at the proposed patch application site
             which may prevent proper placement of the patch.

          -  Subjects for whom a proper assessment of possible application site reactions would be
             confounded by local skin conditions.