A Randomized, Double-blind, Placebo- & Positive-Controlled, Parallel Group, Dose Escalating Study to Evaluate the Effect of Buprenorphine Delivered by Buprenorphine Transdermal System at 10- and 40-mg Dose Levels on QT Intervals in Healthy Adult Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Purdue Pharma LP
- Enrollment
- 132
- Locations
- 1
- Primary Endpoint
- The Comparison of BTDS to Placebo Transdermal System (TDS): the Average Difference From Baseline Using QT Corrected From Within-subject Data (QTci) on Day 13
Study Overview
Brief Summary
The purpose of this study is to examine the effect of buprenorphine on QT interval corrected for heart rate (QTc) in healthy subjects.
Detailed Description
Drugs in this opioid class have been associated with prolonging QT interval/QT interval corrected for heart rate (QTc).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Males and females 18 to 55 years of age, inclusive.
- •Body weight ranging from 50 to 100 kilograms (kg) and a body mass index (BMI) ≤ 30 kg/m
- •Healthy as determined by unremarkable medical history, physical examination, vital signs, laboratory evaluations, electrocardiogram (ECG), and a 24-hour screening ECG telemetry.
- •Willing to refrain from strenuous exercise or contact sports during the study.
- •Female subjects must be surgically sterile or at least 2 years postmenopausal, or using an effective contraceptive method (intrauterine device, hormonal contraceptive, or double-barrier method).
Exclusion Criteria
- •Any clinically significant illness during the 30 days prior to randomization.
- •Any history of allergy to buprenorphine, any excipient of BTDS, opioids, psychotropic or hypnotic drugs, and/or moxifloxacin or any member of the quinolone class of drugs.
- •A clinically significant history of allergic reaction to wound dressings or bandages.
- •Any medical or surgical conditions which might interfere with drug absorption (transdermal or gastrointestinal), distribution, metabolism, or excretion.
- •Abnormalities on physical examination, vital signs, ECG, or clinical laboratory values, unless those abnormalities are judged to be clinically insignificant by the Investigator.
- •Any cardiovascular disorders, including hypertension.
- •Oxygen saturation (SpO2) ≤ 94% as measured by pulse oximetry.
- •Any personal or family history of prolonged QT interval or disorders of cardiac rhythm.
- •Abnormal cardiac condition denoted by any of the following:
- •QT interval ≥ 450 milliseconds (msec).
- •PR interval > 240 msec or ≤ 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 preexcitation, complete left bundle branch block, right bundle branch block (RBBB), or incomplete RBBB.
- •A resting heart rate outside the range of 50 to 85 beats per minute (bpm).
- •Other protocol-specific exclusion/inclusion criteria may apply.
Arms & Interventions
BTDS
Buprenorphine transdermal patches 5, 10, 20, and 2 * 20 mcg/h.
Intervention: Buprenorphine transdermal patch (Drug)
Placebo TDS
Matching placebo transdermal patches 5, 10, 20 and 2 * 20.
Intervention: Matching placebo transdermal patch (Drug)
Moxifloxacin
Moxifloxacin hydrochloride 400 mg tablets
Intervention: Avelox (moxifloxacin hydrochloride) tablet (Drug)
Outcomes
Primary Outcomes
The Comparison of BTDS to Placebo Transdermal System (TDS): the Average Difference From Baseline Using QT Corrected From Within-subject Data (QTci) on Day 13
Time Frame: Baseline to Day 13
Observed time from start of the QRS complex to end of the T wave (QT), and the time between the 2 R waves (RR) data for each of 4 electrocardiographs (ECGs) over an approximate 10-minute interval at each nominal time point. The average QT and QTc data over the 2 pretreatment days were used as the baseline. Observed time from start of the QRS complex to end of the T wave (QT); interval corrected for heart rate (QTc) msec; interval corrected from within-subject data (QTci) msec.
The Comparison of Moxifloxacin to Placebo Transdermal System (TDS): the Average Difference From Baseline Using QT Interval Corrected From Within-subject Data (QTci) on Day 13
Time Frame: Baseline to Day 13
Observed time from start of the QRS complex to end of the T wave (QT), and the time between the 2 R waves (RR) data for each of 4 electrocardiographs (ECGs) over an approximate 10-minute interval at each nominal time point. The average QT and QTc data over the 2 pretreatment days were used as the baseline QT and QTc values. Observed time from start of the QRS complex to end of the T wave (QT); interval corrected for heart rate (QTc) msec; interval corrected from within-subject data (QTci) msec.
Secondary Outcomes
- The Average Differences Between BTDS vs Placebo From Baseline by Interval Corrected From Within-subject Data (QTci) on Day 6(Baseline to Day 6)
- The Average Differences Between Moxifloxacin vs Placebo From Baseline by Interval Corrected From Within-subject Data (QTci) on Day 6(Baseline to Day 6)
- The Average Differences From Baseline Between BTDS and Placebo by Bazett Corrected QT Interval (QTcB) on Day 6 and Day 13(Baseline to Day 6 and Day 13)
- The Average Differences From Baseline Between Moxifloxacin and Placebo of Bazett Corrected QT Interval (QTcB) on Day 6 and Day 13(Baseline to Day 6 and Day 13)
- The Average Differences From Baseline Between BTDS and Placebo by Fridericia's Corrected Interval (QTcF) on Day 6 and Day 13(Baseline to Day 6 and Day 13)
- The Average Differences From Baseline Between Moxifloxacin and Placebo by Fridericia's Corrected Interval (QTcF) on Day 6 and Day 13(Baseline to Day 6 and Day 13)