ECG Effects
Conditions
Keywords
Healthy subjects, Opioid, Transdermal, ECG
Brief summary
The purpose of this study is to evaluate the ECG effects of 10, 40, and 80 mcg/hr buprenorphine delivered by BTDS alone, or by BTDS dosed with naltrexone, relative to placebo in healthy male and female subjects.
Interventions
Buprenorphine patch applied transdermally
Naltrexone tablet; 1 tablet taken orally every 12 hours
DRUGPlacebos (for TDS and for naltrexone and for moxifloxacin)
Matching placebos
Moxifloxacin tablet; 1 tablet taken orally on Days 6, 13 and 17
Sponsors
Purdue Pharma LP
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Provide written informed consent. * Males and females aged 18 to 55, inclusive. * Body weight ranging from 50 to 100 kilograms (kg) (110 to 220 lbs) and body mass index (BMI) ranging from 18 to 30 (kg/m2), inclusive. * Healthy and free of significant abnormal findings as determined by medical history, physical examination, clinical laboratory values, vital signs, and resting 12-lead ECG. * Females of child-bearing potential must be using an adequate and reliable method of contraception (ie, barrier with additional spermicidal foam or jelly, intra-uterine device, hormonal contraception). Females who are postmenopausal must have been postmenopausal ≥ 1 year and have elevated serum follicle stimulating hormone (FSH). * Willing to eat the food supplied during the study. * Willing to refrain from strenuous exercise during the entire study. Subjects will not begin a new exercise program nor participate in any unusually strenuous physical exertion. * All 8 anatomical transdermal system (TDS) application sites (upper back, upper chest, upper outer arm, or lateral thorax) must be acceptable for study use.
Exclusion criteria
* Females who are pregnant (positive beta human chorionic gonadotropin test) or lactating. * Current or recent (within 5 years) history of drug or alcohol abuse. * History or any current conditions that might interfere with drug absorption (transdermal or gastrointestinal), distribution, metabolism or excretion. * Use of an opioid-containing medication in the past 30 days preceding the initial dose in this study. * Known allergy to buprenorphine, any excipient of BTDS, opioids, psychotropic or hypnotic drugs, and/or moxifloxacin or any member of the quinolone class drugs. * Any history of frequent nausea or emesis regardless of etiology. * Any history of seizures or head trauma with sequelae. * Participation in a clinical drug study during the 30 days preceding the initial dose in this study. * Any significant illness during the 30 days preceding the initial dose in this study. * Use of any medication including thyroid hormonal therapy (hormonal contraception and hormonal replacement therapy in the form of estrogen with or without progestin is allowed), vitamins, herbal and/or mineral supplements during the 7 days preceding the initial dose. * Any personal or family history of prolonged QT interval or disorders of cardiac rhythm. * Abnormal cardiac conditions including hypertension. * Abnormal cardiac condition denoted by any of the following: * QTcF interval \> 450 milliseconds (msec) * PR interval \> 240 msec or QRS \> 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 pre-excitation, complete left bundle branch block, right bundle branch block (RBBB), or incomplete RBBB * With a resting heart rate outside the range of 45 to 85 beats per minute (bpm) * Abnormalities on physical examination, vital signs, ECG, or clinical laboratory values, unless those abnormalities were judged clinically insignificant by the investigator. * Oxygen saturation (SpO2) ≤ 94% as measured by pulse oximetry. * Refusal to abstain from caffeine or xanthine containing beverages entirely during confinement. * Refusal to abstain from consumption of alcoholic beverages 48 hours prior to initial study drug administration and any time during study. * History of smoking or use of nicotine products within 45 days of study drug administration or a positive urine cotinine test * Blood or blood products donated within 30 days prior to study drug administration or anytime during the study. * Positive results of urine drug screen or alcohol screen. * Positive results of hepatitis B surface antigen (HBsAg), hepatitis C antibody (anti-HCV). * Positive naloxone challenge test. * Presence of Gilbert's Syndrome, or any known hepatobiliary abnormalities. * The investigator believes the subject to be unsuitable for reason(s) not specifically stated in the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | Baseline to Day 6 | The effects of 10 mcg/hr buprenorphine (Day 6) delivered by BTDS alone, or by BTDS dosed with naltrexone, and naltrexone alone on cardiac repolarization, were assessed based on the corrected QT interval since HR inversely affects QT duration. The time-matched analysis was conducted as the primary endpoint as recommended by ICH E14, with the 2-sided 90% confidence interval for each treatment at each time point showing the placebo- and baseline-corrected (ΔΔ) analysis for QTcI. The effect of BTDS 10 on QT intervals was compared with the moxifloxacin-positive control after placebo and baseline correction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | Baseline to Day 6 | Mean change from baseline for the BTDS 10 mcg/hr dose on Day 6, presented as time-averaged mean change from baseline for BTDS only, BTDS with naltrexone, naltrexone alone, moxifloxacin, and placebo. |
| Heart Rate (HR) | Baseline to Day 6 | Mean change from baseline for the BTDS 10 mcg/hr dose on Day 6, presented as time-averaged mean change from baseline for BTDS only, BTDS with naltrexone, naltrexone alone, moxifloxacin, and placebo. |
| ECG Morphology | Baseline to Day 6 | Morphological analyses were performed with regard to the digital ECG waveform interpretation as defined by a central ECG laboratory's cardiologist blinded to the study treatment. Changes from baseline to each day of treatment were evaluated separately. Any T-U wave complex that suggested an abnormal form compatible with an effect on cardiac repolarization was noted. New ECG morphological onset changes were presented as the percentage of subjects meeting the new criterion (new meant not present on any baseline ECG and became present on at least 1 on-treatment ECG) for the following variables: * Second degree heart block * Third degree heart block * Complete right bundle branch block (RBBB) * Complete left bundle branch block (LBBB) * ST segment changes (elevation and depression separately) * T-wave abnormalities (negative T waves only) * Myocardial infarction (MI) pattern * Any new abnormal U waves |
Countries
United States
Participant flow
Recruitment details
First Subject First Visit: 15-March-2012; Last Subject Last Visit: 10-October-2012. The study was conducted at 1 medical/research site in the United States.
Pre-assignment details
Healthy adult subjects
Participants by arm
| Arm | Count |
|---|---|
| BTDS Buprenorphine transdermal patches 10, 40 (2 x 20) and 80 (4 x 20) mcg/hr
Buprenorphine transdermal patch: Buprenorphine patch applied transdermally | 66 |
| BTDS With Naltrexone Buprenorphine transdermal patches 10, 40 (2 x 20) and 80 (4 x 20) mcg/hr and naltrexone 50 mg tablets
Buprenorphine transdermal patch: Buprenorphine patch applied transdermally
Naltrexone tablet: Naltrexone tablet; 1 tablet taken orally every 12 hours | 66 |
| Naltrexone Naltrexone 50 mg tablets
Naltrexone tablet: Naltrexone tablet; 1 tablet taken orally every 12 hours | 66 |
| Moxifloxacin Moxifloxacin 400-mg tablets
Moxifloxacin tablet: Moxifloxacin tablet; 1 tablet taken orally on Days 6, 13 and 17 | 65 |
| Placebo Matching placebo for transdermal patches and/or naltrexone tablets and/or moxifloxacin tablets
Placebos (for TDS and for naltrexone and for moxifloxacin): Matching placebos | 65 |
| Total | 328 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Administrative | 0 | 0 | 1 | 1 | 2 |
| Overall Study | Adverse Event | 8 | 7 | 2 | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | BTDS | Total | Placebo | Moxifloxacin | Naltrexone | BTDS With Naltrexone |
|---|---|---|---|---|---|---|
| Age, Continuous | 33.3 years STANDARD_DEVIATION 9.27 | 33.4 years STANDARD_DEVIATION 9.8 | 33.0 years STANDARD_DEVIATION 10.48 | 35.0 years STANDARD_DEVIATION 10.03 | 34.0 years STANDARD_DEVIATION 10.14 | 31.6 years STANDARD_DEVIATION 8.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 6 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 115 Participants | 24 Participants | 26 Participants | 22 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 204 Participants | 40 Participants | 38 Participants | 44 Participants | 41 Participants |
| Sex: Female, Male Female | 26 Participants | 127 Participants | 23 Participants | 29 Participants | 22 Participants | 27 Participants |
| Sex: Female, Male Male | 40 Participants | 201 Participants | 42 Participants | 36 Participants | 44 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 59 / 66 | 47 / 66 | 49 / 66 | 37 / 65 | 34 / 65 |
| serious Total, serious adverse events | 1 / 66 | 0 / 66 | 0 / 66 | 0 / 65 | 0 / 65 |
Outcome results
Primary
The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI)
The effects of 40 mcg/hr buprenorphine (Day 13) delivered by BTDS alone, or by BTDS dosed with naltrexone, and naltrexone alone on cardiac repolarization, were assessed based on the corrected QT interval since HR inversely affects QT duration. The time-matched analysis was conducted as the primary endpoint as recommended by ICH E14, with the 2-sided 90% confidence interval for each treatment at each time point showing the placebo- and baseline-corrected (ΔΔ) analysis for QTcI. The effect of BTDS 40 on QT intervals was compared with the moxifloxacin-positive control after placebo and baseline correction.
Time frame: Baseline to Day 13
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.~The placebo treatment group is not presented; however, the placebo data were used as a correction factor for these time-matched analyses.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 9.16 msec |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 5.12 msec |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 1.81 msec |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 10.68 msec |
Primary
The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI)
The effects of 80 mcg/hr buprenorphine (Day 17) delivered by BTDS alone, or by BTDS dosed with naltrexone, and naltrexone alone on cardiac repolarization, were assessed based on the corrected QT interval since HR inversely affects QT duration. The time-matched analysis was conducted as the primary endpoint as recommended by ICH E14, with the 2-sided 90% confidence interval for each treatment at each time point showing the placebo- and baseline-corrected (ΔΔ) analysis for QTcI. The effect of BTDS 80 on QT intervals was compared with the moxifloxacin-positive control after placebo and baseline correction.
Time frame: Baseline to Day 17
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.~The placebo treatment group is not presented; however, the placebo data were used as a correction factor for these time-matched analyses.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 11.46 msec |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 4.47 msec |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 1.50 msec |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 10.78 msec |
Primary
The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI)
The effects of 10 mcg/hr buprenorphine (Day 6) delivered by BTDS alone, or by BTDS dosed with naltrexone, and naltrexone alone on cardiac repolarization, were assessed based on the corrected QT interval since HR inversely affects QT duration. The time-matched analysis was conducted as the primary endpoint as recommended by ICH E14, with the 2-sided 90% confidence interval for each treatment at each time point showing the placebo- and baseline-corrected (ΔΔ) analysis for QTcI. The effect of BTDS 10 on QT intervals was compared with the moxifloxacin-positive control after placebo and baseline correction.
Time frame: Baseline to Day 6
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.~The placebo treatment group is not presented; however, the placebo data were used as a correction factor for these time-matched analyses.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 3.36 milliseconds (msec) |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 5.37 milliseconds (msec) |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 4.34 milliseconds (msec) |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | The Maximum Time-matched Change From Baseline in QT Data Corrected for Heart Rate (QTc), Placebo-corrected, Based on an Individual Correction (QTcI) Method (ΔΔQTcI) | 11.90 milliseconds (msec) |
Secondary
ECG Morphology
Morphological analyses were performed with regard to the digital ECG waveform interpretation as defined by a central ECG laboratory's cardiologist blinded to the study treatment. Changes from baseline to each day of treatment were evaluated separately. Any T-U wave complex that suggested an abnormal form compatible with an effect on cardiac repolarization was noted. New ECG morphological onset changes were presented as the percentage of subjects meeting the new criterion (new meant not present on any baseline ECG and became present on at least 1 on-treatment ECG) for the following variables: * Second degree heart block * Third degree heart block * Complete right bundle branch block (RBBB) * Complete left bundle branch block (LBBB) * ST segment changes (elevation and depression separately) * T-wave abnormalities (negative T waves only) * Myocardial infarction (MI) pattern * Any new abnormal U waves
Time frame: Baseline to Day 13
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 1 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 1 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 1 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 1 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 1 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 1 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| Placebo | ECG Morphology | New ST segment depression changes | 0 Participants |
| Placebo | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Placebo | ECG Morphology | New MI | 0 Participants |
| Placebo | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| Placebo | ECG Morphology | New T wave (negative) inverted | 0 Participants |
| Placebo | ECG Morphology | New abnormal U waves | 0 Participants |
| Placebo | ECG Morphology | New ST segment elevation changes | 1 Participants |
Secondary
ECG Morphology
Morphological analyses were performed with regard to the digital ECG waveform interpretation as defined by a central ECG laboratory's cardiologist blinded to the study treatment. Changes from baseline to each day of treatment were evaluated separately. Any T-U wave complex that suggested an abnormal form compatible with an effect on cardiac repolarization was noted. New ECG morphological onset changes were presented as the percentage of subjects meeting the new criterion (new meant not present on any baseline ECG and became present on at least 1 on-treatment ECG) for the following variables: * Second degree heart block * Third degree heart block * Complete right bundle branch block (RBBB) * Complete left bundle branch block (LBBB) * ST segment changes (elevation and depression separately) * T-wave abnormalities (negative T waves only) * Myocardial infarction (MI) pattern * Any new abnormal U waves
Time frame: Baseline to Day 6
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 1 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 1 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 1 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| Placebo | ECG Morphology | New ST segment depression changes | 0 Participants |
| Placebo | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Placebo | ECG Morphology | New MI | 0 Participants |
| Placebo | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| Placebo | ECG Morphology | New T wave (negative) inverted | 0 Participants |
| Placebo | ECG Morphology | New abnormal U waves | 0 Participants |
| Placebo | ECG Morphology | New ST segment elevation changes | 0 Participants |
Secondary
ECG Morphology
Morphological analyses were performed with regard to the digital ECG waveform interpretation as defined by a central ECG laboratory's cardiologist blinded to the study treatment. Changes from baseline to each day of treatment were evaluated separately. Any T-U wave complex that suggested an abnormal form compatible with an effect on cardiac repolarization was noted. New ECG morphological onset changes were presented as the percentage of subjects meeting the new criterion (new meant not present on any baseline ECG and became present on at least 1 on-treatment ECG) for the following variables: * Second degree heart block * Third degree heart block * Complete right bundle branch block (RBBB) * Complete left bundle branch block (LBBB) * ST segment changes (elevation and depression separately) * T-wave abnormalities (negative T waves only) * Myocardial infarction (MI) pattern * Any new abnormal U waves
Time frame: Baseline to Day 17
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 1 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| BTDS Only (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 1 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 0 Participants |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment depression changes | 1 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New T wave (negative) inverted | 1 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New MI | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New abnormal U waves | 0 Participants |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | ECG Morphology | New ST segment elevation changes | 0 Participants |
| Placebo | ECG Morphology | New ST segment depression changes | 0 Participants |
| Placebo | ECG Morphology | New 2nd or 3rd degree heart block | 0 Participants |
| Placebo | ECG Morphology | New MI | 0 Participants |
| Placebo | ECG Morphology | New complete RBBB & LBBB | 0 Participants |
| Placebo | ECG Morphology | New T wave (negative) inverted | 0 Participants |
| Placebo | ECG Morphology | New abnormal U waves | 0 Participants |
| Placebo | ECG Morphology | New ST segment elevation changes | 0 Participants |
Secondary
Heart Rate (HR)
Mean change from baseline for the BTDS 40 mcg/hr dose on Day 13, presented as time-averaged mean change from baseline for BTDS only, BTDS with naltrexone, naltrexone alone, moxifloxacin, and placebo.
Time frame: Baseline to Day 13
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | 1.3 bpm | Standard Deviation 5.9 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | -1.9 bpm | Standard Deviation 6.3 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | -0.8 bpm | Standard Deviation 3.7 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | 2.3 bpm | Standard Deviation 5 |
| Placebo | Heart Rate (HR) | 1.6 bpm | Standard Deviation 4.5 |
Secondary
Heart Rate (HR)
Mean change from baseline for the BTDS 10 mcg/hr dose on Day 6, presented as time-averaged mean change from baseline for BTDS only, BTDS with naltrexone, naltrexone alone, moxifloxacin, and placebo.
Time frame: Baseline to Day 6
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | -0.1 bpm | Standard Deviation 3.8 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | -1.3 bpm | Standard Deviation 6.8 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | -0.5 bpm | Standard Deviation 2.9 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | 2.0 bpm | Standard Deviation 4.1 |
| Placebo | Heart Rate (HR) | 1.3 bpm | Standard Deviation 3.3 |
Secondary
Heart Rate (HR)
Mean change from baseline for the BTDS 80 mcg/hr dose on Day 17, presented as time-averaged mean change from baseline for BTDS only, BTDS with naltrexone, naltrexone alone, moxifloxacin, and placebo.
Time frame: Baseline to Day 17
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | 1.3 bpm | Standard Deviation 4.9 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | -2.4 bpm | Standard Deviation 5.6 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | -0.8 bpm | Standard Deviation 3.9 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | Heart Rate (HR) | 2.5 bpm | Standard Deviation 4.4 |
| Placebo | Heart Rate (HR) | 1.5 bpm | Standard Deviation 4 |
Secondary
QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval
Mean change from baseline for the BTDS 80 mcg/hr dose on Day 17, presented as time-averaged mean change from baseline for BTDS only, BTDS with naltrexone, naltrexone alone, moxifloxacin, and placebo.
Time frame: Baseline to Day 17
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | 10.4 msec | Standard Deviation 9 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | 9.0 msec | Standard Deviation 7.6 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 5.4 msec | Standard Deviation 8.9 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 6.1 msec | Standard Deviation 13.9 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 0.4 msec | Standard Deviation 3 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 7.1 msec | Standard Deviation 17.1 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | 1.8 msec | Standard Deviation 8.6 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | -0.8 msec | Standard Deviation 8.7 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 5.8 msec | Standard Deviation 5.5 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 1.5 msec | Standard Deviation 2.3 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | -1.7 msec | Standard Deviation 7.9 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 4.3 msec | Standard Deviation 5.7 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | -0.8 msec | Standard Deviation 7.4 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 1.3 msec | Standard Deviation 1.9 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 0.8 msec | Standard Deviation 12.6 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 0.2 msec | Standard Deviation 2.8 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | 6.7 msec | Standard Deviation 6.4 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 1.4 msec | Standard Deviation 11.9 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 3.8 msec | Standard Deviation 10.9 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | 9.3 msec | Standard Deviation 7.7 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 3.0 msec | Standard Deviation 5.3 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | -3.7 msec | Standard Deviation 11.7 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 0.6 msec | Standard Deviation 1.6 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | 1.2 msec | Standard Deviation 7.6 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | -0.4 msec | Standard Deviation 6.6 |
Secondary
QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval
Mean change from baseline for the BTDS 10 mcg/hr dose on Day 6, presented as time-averaged mean change from baseline for BTDS only, BTDS with naltrexone, naltrexone alone, moxifloxacin, and placebo.
Time frame: Baseline to Day 6
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 0.4 msec | Standard Deviation 2.1 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | -0.1 msec | Standard Deviation 5.9 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 0.3 msec | Standard Deviation 11.2 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | -0.3 msec | Standard Deviation 6.1 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 4.7 msec | Standard Deviation 7.2 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 0.7 msec | Standard Deviation 1.9 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 2.4 msec | Standard Deviation 5 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | 1.5 msec | Standard Deviation 6.6 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 5.6 msec | Standard Deviation 22.1 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | 2.9 msec | Standard Deviation 8.7 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 2.1 msec | Standard Deviation 4.2 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | 1.5 msec | Standard Deviation 4.6 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | 0.9 msec | Standard Deviation 5.4 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 0.6 msec | Standard Deviation 1.4 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 2.6 msec | Standard Deviation 8.8 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 2.6 msec | Standard Deviation 11.9 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | 6.9 msec | Standard Deviation 5.1 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | -0.2 msec | Standard Deviation 1.9 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 0.3 msec | Standard Deviation 6.1 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | 9.1 msec | Standard Deviation 5.2 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 0.6 msec | Standard Deviation 4.4 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 0.0 msec | Standard Deviation 1.5 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | -0.8 msec | Standard Deviation 5.4 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | -3.4 msec | Standard Deviation 8.6 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | 0.5 msec | Standard Deviation 7 |
Secondary
QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval
Mean change from baseline for the BTDS 40 mcg/hr dose on Day 13, presented as time-averaged mean change from baseline for BTDS only, BTDS with naltrexone, naltrexone alone, moxifloxacin, and placebo.
Time frame: Baseline to Day 13
Population: The full analysis for ECG population was the group of subjects who were randomized, received at least 1 dose of study drug, and had at least 1 time-matched baseline and 1 on-treatment ECG.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 0.2 msec | Standard Deviation 2.8 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | 5.0 msec | Standard Deviation 7.8 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 2.4 msec | Standard Deviation 16 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | 6.3 msec | Standard Deviation 8.8 |
| BTDS Only (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 4.5 msec | Standard Deviation 8.7 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 0.9 msec | Standard Deviation 2.4 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 4.4 msec | Standard Deviation 5.9 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | -1.1 msec | Standard Deviation 8 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 5.5 msec | Standard Deviation 20.8 |
| BTDS With Naltrexone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | 1.1 msec | Standard Deviation 9.6 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 3.2 msec | Standard Deviation 9.1 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | -1.3 msec | Standard Deviation 6.2 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | -2.2 msec | Standard Deviation 6.8 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 1.3 msec | Standard Deviation 2 |
| Naltrexone Alone (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 0.4 msec | Standard Deviation 11.3 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | 0.9 msec | Standard Deviation 13.8 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | 5.6 msec | Standard Deviation 6.6 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | -0.2 msec | Standard Deviation 2.6 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 1.3 msec | Standard Deviation 6.6 |
| Moxifloxacin (Placebo-corrected ΔΔQTcI) | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | 8.0 msec | Standard Deviation 7 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | PR | 2.0 msec | Standard Deviation 5.5 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QRS | 0.3 msec | Standard Deviation 1.8 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcF | -1.6 msec | Standard Deviation 6.2 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QT | -5.1 msec | Standard Deviation 12.6 |
| Placebo | QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval | QTcB | 0.2 msec | Standard Deviation 7.2 |