The Effect of Buprenorphine Delivered by Buprenorphine Transdermal System (BTDS) on QT Intervals in Healthy Volunteers

Phase 1

Completed

Conditions: Healthy Volunteers

Interventions: Drug: Buprenorphine transdermal patch
Drug: Matching placebo transdermal patch
Drug: Avelox (moxifloxacin hydrochloride) tablet

Registration Number: NCT01148537

Lead Sponsor: Purdue Pharma LP

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 132

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/m2.
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BTDS	Buprenorphine transdermal patch	Buprenorphine transdermal patches 5, 10, 20, and 2 \* 20 mcg/h.
Placebo TDS	Matching placebo transdermal patch	Matching placebo transdermal patches 5, 10, 20 and 2 \* 20.
Moxifloxacin	Avelox (moxifloxacin hydrochloride) tablet	Moxifloxacin hydrochloride 400 mg tablets

Primary Outcome Measures

Name	Time	Method
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	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	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 Outcome Measures

Name	Time	Method
The Average Differences Between BTDS vs Placebo From Baseline by Interval Corrected From Within-subject Data (QTci) on Day 6	Baseline to Day 6	QT and RR data were determined for each of 4 ECGs over an approximate 10-minute interval at each nominal time point. The average QT and QTc data from the replicate ECGs at each nominal time point were calculated. 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.
The Average Differences Between Moxifloxacin vs Placebo From Baseline by Interval Corrected From Within-subject Data (QTci) on Day 6	Baseline to Day 6	QT and RR data were determined for each of 4 ECGs over an approximate 10-minute interval at each nominal time point. The average QT and QTc data from the replicate ECGs at each nominal time point were calculated. 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.
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	QT and RR data were determined for each of 4 ECGs over an approximate 10-minute interval at each nominal time point. The average QT and QTc (QT interval corrected for heart rate) data from the replicate ECGs at each nominal time point were calculated. 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 by Bazett's method (QTcB) msec.
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	QT and RR data were determined for each of 4 ECGs over an approximate 10-minute interval at each nominal time point. The average QT and QTc data from the replicate ECGs at each nominal time point were calculated. 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 by Bazett's method (QTcB) msec.
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	QT and RR data were determined for each of 4 ECGs over an approximate 10-minute interval at each nominal time point. The average QT and QTc (interval corrected for heart rate) data from the replicate ECGs at each nominal time point were calculated. 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 by Fridericia's method (QTcF) msec.
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	QT and RR data were determined for each of 4 ECGs over an approximate 10-minute interval at each nominal time point. The average QT and QTc (interval corrected for heart rate) data from the replicate ECGs at each nominal time point were calculated. 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 by Fridericia's method (QTcF) msec.