The Effect of Buprenorphine Delivered by Buprenorphine Transdermal System (BTDS) at Doses up to 80 Micrograms/Hour (mcg/hr) and Naltrexone on Electrocardiogram (ECG) Intervals in Healthy Volunteers

NCT ID: NCT01999114

Last Updated: 2018-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 328 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2012-10-31

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.

Conditions

ECG Effects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

BTDS

Buprenorphine transdermal patches 10, 40 (2 x 20), and 80 (4 x 20) mcg/hr

Group Type: EXPERIMENTAL

Buprenorphine transdermal patch

Intervention Type: DRUG

Buprenorphine patch applied transdermally

BTDS with naltrexone

Buprenorphine transdermal patches 10, 40 (2 x 20), and 80 (4 x 20) mcg/hr and naltrexone 50 mg tablets

Group Type: EXPERIMENTAL

Buprenorphine transdermal patch

Intervention Type: DRUG

Buprenorphine patch applied transdermally

Naltrexone tablet

Intervention Type: DRUG

Naltrexone tablet; 1 tablet taken orally every 12 hours

Naltrexone

Naltrexone 50 mg tablets

Group Type: ACTIVE_COMPARATOR

Naltrexone tablet

Intervention Type: DRUG

Naltrexone tablet; 1 tablet taken orally every 12 hours

Placebo

Matching placebo for transdermal patches and/or naltrexone tablets and/or moxifloxacin tablets

Group Type: PLACEBO_COMPARATOR

Placebos (for TDS and for naltrexone and for moxifloxacin)

Intervention Type: DRUG

Matching placebos

Moxifloxacin

Moxifloxacin 400-mg tablets

Group Type: ACTIVE_COMPARATOR

Moxifloxacin tablet

Intervention Type: DRUG

Moxifloxacin tablet; 1 tablet taken orally on Days 6, 13 and 17

Interventions

Buprenorphine transdermal patch

Buprenorphine patch applied transdermally

Intervention Type: DRUG

Naltrexone tablet

Naltrexone tablet; 1 tablet taken orally every 12 hours

Intervention Type: DRUG

Placebos (for TDS and for naltrexone and for moxifloxacin)

Matching placebos

Intervention Type: DRUG

Moxifloxacin tablet

Moxifloxacin tablet; 1 tablet taken orally on Days 6, 13 and 17

Intervention Type: DRUG

Other Intervention Names

Butrans; ReVia; Avelox®

Eligibility Criteria

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.
• Subjects who have allergies or other contraindications to transdermal systems or patch adhesives.
• Clinically significant history of allergic reaction to wound dressings or elastoplast.
• Subjects with a dermatological disorder at any relevant patch application site that precludes proper placement and/or rotation of patch.
• Taking antihistamines within 72 hours prior to dosing or systemic or topical corticosteroids within 3 weeks prior to dosing.
• Subjects will not allow hair to be removed at the proposed patch application site which may prevent proper placement of the patch.
• Subjects for whom a proper assessment of possible application site reactions would be confounded by local skin conditions.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Purdue Pharma LP

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

PPD Phase I Clinic

Austin, Texas, United States

Countries

United States

References

Harris SC, Morganroth J, Ripa SR, Thorn MD, Colucci S. Effects of buprenorphine on QT intervals in healthy subjects: results of 2 randomized positive- and placebo-controlled trials. Postgrad Med. 2017 Jan;129(1):69-80. doi: 10.1080/00325481.2017.1270156.

Reference Type: RESULT

PMID: 27927048 (View on PubMed)

Other Identifiers

BUP1025

Identifier Type: -

Identifier Source: org_study_id