Open-Label, Safety Study of Lofexidine (NU LEAF)

A Phase 3, Open-Label, Safety Study of Lofexidine

The purpose of this Phase 3 open-label treatment study is to evaluate the safety and effectiveness of lofexidine at a clinically relevant dose to alleviate symptoms of acute withdrawal from any opioid, including methadone and buprenorphine. This study will take place in a variety of clinical scenarios, both in-clinic and outpatient settings.

Study Overview

• Status: Completed
• Conditions: Opioid Withdrawal
• Intervention / Treatment: Drug: Lofexidine

Detailed Description

Eligible subjects (person seeking treatment for partial or total opioid withdrawal) enrolled in this study are required to take lofexidine for a minimum of 7 days.

• Study Type: Interventional
• Enrollment (Actual): 286
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
    • Springdale, Arkansas, United States, 72764
  • California
    • San Diego, California, United States, 92103
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
    • Hollywood, Florida, United States, 33021
    • Orlando, Florida, United States, 32801
  • Georgia
    • Atlanta, Georgia, United States, 30331
  • Illinois
    • Winfield, Illinois, United States, 60190
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
  • Maryland
    • Rockville, Maryland, United States, 20853
  • Mississippi
    • Flowood, Mississippi, United States, 39232
  • Missouri
    • Saint Louis, Missouri, United States, 63141
  • New York
    • New York, New York, United States, 10019
  • Ohio
    • Dayton, Ohio, United States, 45417
  • Oregon
    • Portland, Oregon, United States, 97214
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
  • Utah
    • Orem, Utah, United States, 84058

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female at least 18 years of age
• Must be able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures
• Must have current dependence, according to the Mini International Neuropsychiatric Interview (M.I.N.I.), on any opioid (including methadone and buprenorphine maintenance treatment)
• Must be seeking treatment for partial or total withdrawal from current opioid and expected, as determined by the Principal Investigator, to benefit from lofexidine treatment for at least 7 days at clinically relevant doses. This can include a variety of clinical situations where opioid withdrawal illness is likely to occur including abrupt and total withdrawal (including from methadone and buprenorphine), agonist-assisted total withdrawal, dose reduction of maintenance treatment (e.g., methadone, buprenorphine) and transition from an opioid agonist to naltrexone or buprenorphine maintenance
• Must have Urine toxicology screen result of positive for opioid(s) relevant to the subject's withdrawal treatment goal
• If female and of childbearing potential, subject must agree to use of one of the following methods of birth control including oral contraceptives, patch, barrier (diaphragm, sponge or condom) plus spermicidal preparations, intrauterine contraceptive system, levonorgestrel implant, medroxyprogesterone acetate contraceptive injection, complete abstinence from sexual intercourse, hormonal vaginal contraceptive ring or surgical sterilization or partner sterile (with documented proof)

Exclusion Criteria:

• Female subject who is pregnant or lactating
• History of very serious medical illness not under control including, but not limited to, active self-reported acquired immune deficiency syndrome (AIDS) or self-reported human immunodeficiency virus (HIV) positive status and taking retroviral medications currently or within the past 4 weeks and/or having an unstable psychiatric condition. These conditions will be determined at Screening by medical history, physical examination, 12 lead electrocardiogram (duplicate), clinical laboratory tests for infectious diseases, and a tuberculin test
• Current dependence (based on the M.I.N.I.) on any psychoactive substance (excluding caffeine, nicotine, and the subject's current opioid-dependence agent, which can include methadone and buprenorphine, for example, in agonist-maintained subjects) that requires detoxification or dose reduction as part of the pre-defined individual subject withdrawal treatment goal
• Have participated in an investigational drug study within the past 30 days
• Have a history of lofexidine exposure in a prior clinical trial or otherwise
• Have an abnormal cardiovascular exam at screening
• Any subject that requires tricyclic antidepressants, which may reduce the efficacy of imidazoline derivatives and/or beta-receptor blockers, to avoid the risk of excessive bradycardia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Open Label Lofexidine; During this open-label study, subjects will be given the option to receive lofexidine tablets for 7 days and up to 14 days if requested.	Drug: Lofexidine; All enrolled subjects will take lofexidine orally for 7 days, starting on Day 1 at a dose of 3.2 mg per day (0.8 mg QID), with lowering of the dose allowed to 2.4 mg daily (0.6 mg QID) if required for tolerability based on the subject's individual treatment goal and response per clinical judgment of the Principal Investigator.; Other Names: Lofexidine hydrochloride (HCL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Occurrence of Treatment Emergent Adverse Events (TEAEs)	Subjects with at least 1 TEAE occurring on days 1-14.	Days 1-14
Overall Occurrence of Serious Treatment Emergent Adverse Events (Serious TEAEs)		Days 1-14
Overall Treatment Emergent Adverse Events (TEAEs) by Severity		Days 1-14
Occurrence of Per Protocol Adverse Events of Special Interest (AESI)		Day 1 to Day 14
Occurrence of Adverse Events (AEs) Not Related to Opioid Withdrawal		Day 1 to Day 14
Mean Observed and Change From Screening in Seated Systolic Blood Pressure (mmHg): Vital Sign	Baseline vital signs were defined by the assessment value at screening when subjects were not experiencing opioid withdrawal to reduce the potential for variability from the effects of different states of withdrawal that may have been present before dosing on Day 1. Overall screening values are captured in the column "Inpatient: Pre 8AM"; these values were recorded at various times for each participant during the screening visit, not necessarily at 8AM. Serial vital sign assessments required for inpatient visits on days 1-3, either inpatient or outpatient for days 4-7, and outpatient only for days 8-14. Day 14 only required pre-dose vital signs measurement. Day 1 Change, Pre 8AM was prior to the first dose.	Day 1 to Day 14
Mean Observed and Change From Screening in Standing Systolic Blood Pressure (mmHg): Vital Sign	Baseline vital signs were defined by the assessment value at screening when subjects were not experiencing opioid withdrawal to reduce the potential for variability from the effects of different states of withdrawal that may have been present before dosing on Day 1. Overall screening values are captured in the column "Inpatient: Pre 8AM"; these values were recorded at various times for each participant during the screening visit, not necessarily at 8AM. Serial vital sign assessments required for inpatient visits on days 1-3, either inpatient or outpatient for days 4-7, and outpatient only for days 8-14. Day 14 only required pre-dose vital signs measurement. Day 1 Change, Pre 8AM was prior to the first dose.	Day 1 to Day 14
Mean Observed and Change From Screening in Seated Diastolic Blood Pressure (mmHg): Vital Sign	Baseline vital signs were defined by the assessment value at screening when subjects were not experiencing opioid withdrawal to reduce the potential for variability from the effects of different states of withdrawal that may have been present before dosing on Day 1. Overall screening values are captured in the column "Inpatient: Pre 8AM"; these values were recorded at various times for each participant during the screening visit, not necessarily at 8AM. Serial vital sign assessments required for inpatient visits on days 1-3, either inpatient or outpatient for days 4-7, and outpatient only for days 8-14. Day 14 only required pre-dose vital signs measurement. Day 1 Change, Pre 8AM was prior to the first dose.	Day 1 to Day 14
Mean Observed and Change From Screening in Standing Diastolic Blood Pressure (mmHg): Vital Sign	Baseline vital signs were defined by the assessment value at screening when subjects were not experiencing opioid withdrawal to reduce the potential for variability from the effects of different states of withdrawal that may have been present before dosing on Day 1. Overall screening values are captured in the column "Inpatient: Pre 8AM"; these values were recorded at various times for each participant during the screening visit, not necessarily at 8AM. Serial vital sign assessments required for inpatient visits on days 1-3, either inpatient or outpatient for days 4-7, and outpatient only for days 8-14. Day 14 only required pre-dose vital signs measurement. Day 1 Change, Pre 8AM was prior to the first dose.	Day 1 to Day 14
Mean Observed and Change From Screening in Seated Pulse (Bpm): Vital Signs	Baseline vital signs were defined by the assessment value at screening when subjects were not experiencing opioid withdrawal to reduce the potential for variability from the effects of different states of withdrawal that may have been present before dosing on Day 1. Overall screening values are captured in the column "Inpatient: Pre 8AM"; these values were recorded at various times for each participant during the screening visit, not necessarily at 8AM. Serial vital sign assessments required for inpatient visits on days 1-3, either inpatient or outpatient for days 4-7, and outpatient only for days 8-14. Day 14 only required pre-dose vital signs measurement. Day 1 Change, Pre 8AM was prior to the first dose.	Day 1 to Day 14
Mean Observed and Change From Screening in Standing Pulse (Bpm): Vital Signs	Baseline vital signs were defined by the assessment value at screening when subjects were not experiencing opioid withdrawal to reduce the potential for variability from the effects of different states of withdrawal that may have been present before dosing on Day 1. Overall screening values are captured in the column "Inpatient: Pre 8AM"; these values were recorded at various times for each participant during the screening visit, not necessarily at 8AM. Serial vital sign assessments required for inpatient visits on days 1-3, either inpatient or outpatient for days 4-7, and outpatient only for days 8-14. Day 14 only required pre-dose vital signs measurement. Day 1 Change, Pre 8AM was prior to the first dose.	Day 1 to Day 14
Columbia Suicide Severity Rating Scale Questionnaire (C-SSRS): Suicidal Ideation and Behavior Numbers	The C-SSRS measures both suicidal ideation and suicidal behavior and will be completed to assess lifetime suicidality before first dose of study drug, 3.5 hours after first daily dose of study drug on in-clinic treatment days, and then once a day before dosing during outpatient treatment days. C-SSRS will also be assessed at end of study/discontinuation.	Day 1 to Day 14
Clinical Laboratory Test Change From Baseline: Hematology	Hematology Parameters with Shifts in ≥3% of Subjects from Screening to End of Study	Day 1 to Day 14
Clinical Laboratory Test Change From Baseline: Chemistry	Chemistry Parameters with Shifts in ≥3% of Subjects from Screening to End of Study	Day 1 to Day 14
Clinical Laboratory Test Change From Baseline: Urinalysis		Day 1 to Day 7
Safety Electrocardiograms (ECG) Evaluation Shift From Baseline to Post Dose and End of Study	For each 12-lead ECG obtained during the study, the investigator made an overall interpretation of the ECG (normal, abnormal NCS, and abnormal CS). Shifts from normal at baseline to abnormal NCS and abnormal CS at the end of study predose and postdose assessments were summarized.	Day 1 and Day 14

Collaborators and Investigators

• Sponsor: USWM, LLC (dba US WorldMeds)
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Study Director: Charles W Gorodetzky, MD, PhD, US WorldMeds

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: February 9, 2015
• First Submitted That Met QC Criteria: February 9, 2015
• First Posted (Estimate): February 16, 2015

Study Record Updates

• Last Update Posted (Actual): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 11, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: detoxification; agonist taper; methadone step down; buprenorphine step down; opioid withdrawal syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Substance Withdrawal Syndrome; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Narcotic Antagonists; Sympatholytics; Clonidine; Lofexidine
• Other Study ID Numbers: USWM-LX1-3003-2; 1U01DA033276-01A1 (U.S. NIH Grant/Contract)