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

NCT01999114 | Completed Phase 1 Results DMC

• 1 other identifier: BUP1025
• Study Type: interventional
• Target: 328
• Locations: 1 country
• Sites: 1

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

Keywords

Healthy subjects; Opioid; Transdermal; ECG

Outcome Measures

Primary Outcomes (3)

• 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.

  Baseline to Day 6

• 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.

  Baseline to Day 13

• 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.

  Baseline to Day 17

Secondary Outcomes (9)

• QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval

  Baseline to Day 6

• Heart Rate (HR)

  Baseline to Day 6

• QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval

  Baseline to Day 13

• Heart Rate (HR)

  Baseline to Day 13

• QTcF and QTcB for Historical Purposes, PR Interval, QRS Interval, and Uncorrected QT Interval

  Baseline to Day 17

Study Arms (5)

BTDS

EXPERIMENTAL

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

Drug: Buprenorphine transdermal patch

BTDS with naltrexone

EXPERIMENTAL

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

Drug: Buprenorphine transdermal patch; Drug: Naltrexone tablet

Naltrexone

ACTIVE COMPARATOR

Naltrexone 50 mg tablets

Drug: Naltrexone tablet

Placebo

PLACEBO COMPARATOR

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

Drug: Placebos (for TDS and for naltrexone and for moxifloxacin)

Moxifloxacin

ACTIVE COMPARATOR

Moxifloxacin 400-mg tablets

Drug: Moxifloxacin tablet

Interventions

Buprenorphine transdermal patch DRUG

Buprenorphine patch applied transdermally

Also known as: Butrans

BTDS; BTDS with naltrexone

Naltrexone tablet DRUG

Naltrexone tablet; 1 tablet taken orally every 12 hours

Also known as: ReVia

BTDS with naltrexone; Naltrexone

Placebos (for TDS and for naltrexone and for moxifloxacin) DRUG

Matching placebos

Placebo

Moxifloxacin tablet DRUG

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

Also known as: Avelox®

Moxifloxacin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Purdue Pharma LP: lead

Study Sites (1)

PPD Phase I Clinic

Austin, Texas, 78744, United States

Location

Related Publications (1)

• 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.

  PMID: 27927048 RESULT

MeSH Terms

Interventions

Buprenorphine; Naltrexone; Moxifloxacin

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Naloxone; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring

Results Point of Contact

• Title: Clinical Leader
• Organization: Purdue Pharma L.P.

stephen.harris@pharma.com

800-733-1333

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2013
• First Posted: December 3, 2013
• Study Start: March 1, 2012
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: November 5, 2018
• Results First Posted: November 5, 2018

Record last verified: 2018-02

Locations

US (1)