The Effect of Buprenorphine Delivered by Buprenorphine Transdermal System (BTDS) on QT Intervals in Healthy Volunteers
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Purpose
The purpose of this study is to examine the effect of buprenorphine on QT interval corrected for heart rate (QTc) in healthy subjects.
| Condition | Intervention | Phase |
|---|---|---|
|
Healthy Volunteers |
Drug: Buprenorphine transdermal patch Drug: Matching placebo transdermal patch Drug: Avelox (moxifloxacin hydrochloride) tablet |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| 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 |
- 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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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.
- 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 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Baseline to Day 6 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Baseline to Day 6 and Day 13 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Baseline to Day 6 and Day 13 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Baseline to Day 6 and Day 13 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Baseline to Day 6 and Day 13 ] [ Designated as safety issue: Yes ]
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.
| Enrollment: | 132 |
| Study Start Date: | July 2004 |
| Study Completion Date: | December 2004 |
| Primary Completion Date: | December 2004 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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 Name: 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 Name: Avelox
|
Detailed Description:
Drugs in this opioid class have been associated with prolonging QT interval/QT interval corrected for heart rate (QTc).
Eligibility| Ages Eligible for Study: | 18 Years to 55 Years |
| Genders Eligible for Study: | Both |
| 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/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.
Contacts and Locations More Information
Additional Information:
No publications provided
| Responsible Party: | Purdue Pharma LP |
| ClinicalTrials.gov Identifier: | NCT01148537 History of Changes |
| Other Study ID Numbers: | BUP1011 |
| Study First Received: | June 21, 2010 |
| Results First Received: | July 28, 2010 |
| Last Updated: | August 27, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Purdue Pharma LP:
|
Healthy subjects Opioid Transdermal |
Additional relevant MeSH terms:
|
Buprenorphine Moxifloxacin Norgestimate, ethinyl estradiol drug combination Analgesics, Opioid Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents |
Therapeutic Uses Central Nervous System Depressants Narcotic Antagonists Narcotics Anti-Infective Agents Contraceptives, Oral, Combined Contraceptives, Oral Contraceptive Agents, Female Contraceptive Agents Reproductive Control Agents |
ClinicalTrials.gov processed this record on June 18, 2013