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

August 27, 2012 updated by: Purdue Pharma LP

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

The purpose of this study is to examine the effect of buprenorphine on QT interval corrected for heart rate (QTc) in healthy subjects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Drugs in this opioid class have been associated with prolonging QT interval/QT interval corrected for heart rate (QTc).

Study Type

Interventional

Enrollment (Actual)

132

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Austin, Texas, United States, 78704
        • PPD Development, LP, Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: BTDS
Buprenorphine transdermal patches 5, 10, 20, and 2 * 20 mcg/h.
Drug: Buprenorphine transdermal patch
Buprenorphine transdermal patch 5, 10, 20, and 2 * 20 mcg/h.
Other Names:
  • Butrans™
PLACEBO_COMPARATOR: Placebo TDS
Matching placebo transdermal patches 5, 10, 20 and 2 * 20.
Drug: Matching placebo transdermal patch
Placebo transdermal patch to match BTDS 5, 10, 20, and 2 * 20.
ACTIVE_COMPARATOR: Moxifloxacin
Moxifloxacin hydrochloride 400 mg tablets
Drug: Avelox (moxifloxacin hydrochloride) tablet
Moxifloxacin 400 mg tablet; 1 tablet taken orally on days 6 and 13
Other Names:
  • Avelox

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to Day 13
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.
Baseline to Day 13

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Average Differences Between BTDS vs Placebo From Baseline by Interval Corrected From Within-subject Data (QTci) on Day 6
Time Frame: 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.
Baseline to Day 6
The Average Differences Between Moxifloxacin vs Placebo From Baseline by Interval Corrected From Within-subject Data (QTci) on Day 6
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
Baseline to Day 6 and Day 13

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Purdue Pharma LP

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Primary Completion (ACTUAL)

December 1, 2004

Study Completion (ACTUAL)

December 1, 2004

Study Registration Dates

First Submitted

June 21, 2010

First Submitted That Met QC Criteria

June 21, 2010

First Posted (ESTIMATE)

June 22, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

September 3, 2012

Last Update Submitted That Met QC Criteria

August 27, 2012

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BUP1011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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