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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01148537
• Other study ID #: BUP1011
• Status: Completed
• Phase: Phase 1
• First received: June 21, 2010
• Last updated: August 27, 2012
• Start date: July 2004
• Est. completion date: December 2004

Study information

• Verified date: August 2012
• Source: Purdue Pharma LP
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: December 2004
• Est. primary completion date: December 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Buprenorphine transdermal patch
Buprenorphine transdermal patch 5, 10, 20, and 2 * 20 mcg/h.
• Matching placebo transdermal patch
Placebo transdermal patch to match BTDS 5, 10, 20, and 2 * 20.
• Avelox (moxifloxacin hydrochloride) tablet
Moxifloxacin 400 mg tablet; 1 tablet taken orally on days 6 and 13

Locations

Country	Name	City	State
United States	PPD Development, LP, Clinics	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Purdue Pharma LP

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	Yes
Primary	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	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	Yes
Secondary	The Average Differences Between BTDS vs Placebo From Baseline by Interval Corrected From Within-subject Data (QTci) on 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	Yes
Secondary	The Average Differences Between Moxifloxacin vs Placebo From Baseline by Interval Corrected From Within-subject Data (QTci) on 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	Yes
Secondary	The Average Differences From Baseline Between BTDS and Placebo by Bazett Corrected QT Interval (QTcB) on 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	Yes
Secondary	The Average Differences From Baseline Between Moxifloxacin and Placebo of Bazett Corrected QT Interval (QTcB) on 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	Yes
Secondary	The Average Differences From Baseline Between BTDS and Placebo by Fridericia's Corrected Interval (QTcF) on 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	Yes
Secondary	The Average Differences From Baseline Between Moxifloxacin and Placebo by Fridericia's Corrected Interval (QTcF) on 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	Yes

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