Back to resultsOpen-Label, Safety Study of Lofexidine (NU LEAF)
Primary Purpose
Opioid Withdrawal
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Lofexidine
Sponsored by
About this trial
This is an interventional treatment trial for Opioid Withdrawal focused on measuring detoxification, agonist taper, methadone step down, buprenorphine step down, opioid withdrawal syndrome
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Open Label Lofexidine
Arm Description
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.
Outcomes
Primary Outcome Measures
Overall Occurrence of Treatment Emergent Adverse Events (TEAEs)
Subjects with at least 1 TEAE occurring on days 1-14.
Overall Occurrence of Serious Treatment Emergent Adverse Events (Serious TEAEs)
Overall Treatment Emergent Adverse Events (TEAEs) by Severity
Occurrence of Per Protocol Adverse Events of Special Interest (AESI)
Occurrence of Adverse Events (AEs) Not Related to Opioid Withdrawal
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.
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.
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.
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.
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.
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.
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.
Clinical Laboratory Test Change From Baseline: Hematology
Hematology Parameters with Shifts in ≥3% of Subjects from Screening to End of Study
Clinical Laboratory Test Change From Baseline: Chemistry
Chemistry Parameters with Shifts in ≥3% of Subjects from Screening to End of Study
Clinical Laboratory Test Change From Baseline: Urinalysis
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT02363998
First Posted
February 9, 2015
Last Updated
March 11, 2022
Sponsor
USWM, LLC (dba US WorldMeds)
Collaborators
National Institute on Drug Abuse (NIDA)
1. Study Identification
Unique Protocol Identification Number
NCT02363998
Brief Title
Open-Label, Safety Study of Lofexidine
Acronym
NU LEAF
Official Title
A Phase 3, Open-Label, Safety Study of Lofexidine
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
February 2015 (Actual)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
USWM, LLC (dba US WorldMeds)
Collaborators
National Institute on Drug Abuse (NIDA)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Withdrawal
Keywords
detoxification, agonist taper, methadone step down, buprenorphine step down, opioid withdrawal syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
286 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Open Label Lofexidine
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Lofexidine
Other Intervention Name(s)
Lofexidine hydrochloride (HCL)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Occurrence of Treatment Emergent Adverse Events (TEAEs)
Description
Subjects with at least 1 TEAE occurring on days 1-14.
Time Frame
Days 1-14
Title
Overall Occurrence of Serious Treatment Emergent Adverse Events (Serious TEAEs)
Time Frame
Days 1-14
Title
Overall Treatment Emergent Adverse Events (TEAEs) by Severity
Time Frame
Days 1-14
Title
Occurrence of Per Protocol Adverse Events of Special Interest (AESI)
Time Frame
Day 1 to Day 14
Title
Occurrence of Adverse Events (AEs) Not Related to Opioid Withdrawal
Time Frame
Day 1 to Day 14
Title
Mean Observed and Change From Screening in Seated Systolic Blood Pressure (mmHg): Vital Sign
Description
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.
Time Frame
Day 1 to Day 14
Title
Mean Observed and Change From Screening in Standing Systolic Blood Pressure (mmHg): Vital Sign
Description
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.
Time Frame
Day 1 to Day 14
Title
Mean Observed and Change From Screening in Seated Diastolic Blood Pressure (mmHg): Vital Sign
Description
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.
Time Frame
Day 1 to Day 14
Title
Mean Observed and Change From Screening in Standing Diastolic Blood Pressure (mmHg): Vital Sign
Description
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.
Time Frame
Day 1 to Day 14
Title
Mean Observed and Change From Screening in Seated Pulse (Bpm): Vital Signs
Description
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.
Time Frame
Day 1 to Day 14
Title
Mean Observed and Change From Screening in Standing Pulse (Bpm): Vital Signs
Description
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.
Time Frame
Day 1 to Day 14
Title
Columbia Suicide Severity Rating Scale Questionnaire (C-SSRS): Suicidal Ideation and Behavior Numbers
Description
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.
Time Frame
Day 1 to Day 14
Title
Clinical Laboratory Test Change From Baseline: Hematology
Description
Hematology Parameters with Shifts in ≥3% of Subjects from Screening to End of Study
Time Frame
Day 1 to Day 14
Title
Clinical Laboratory Test Change From Baseline: Chemistry
Description
Chemistry Parameters with Shifts in ≥3% of Subjects from Screening to End of Study
Time Frame
Day 1 to Day 14
Title
Clinical Laboratory Test Change From Baseline: Urinalysis
Time Frame
Day 1 to Day 7
Title
Safety Electrocardiograms (ECG) Evaluation Shift From Baseline to Post Dose and End of Study
Description
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.
Time Frame
Day 1 and Day 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles W Gorodetzky, MD, PhD
Organizational Affiliation
US WorldMeds
Official's Role
Study Director
Facility Information:
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72211
Country
United States
City
Springdale
State/Province
Arkansas
ZIP/Postal Code
72764
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32801
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30331
Country
United States
City
Winfield
State/Province
Illinois
ZIP/Postal Code
60190
Country
United States
City
Lake Charles
State/Province
Louisiana
ZIP/Postal Code
70629
Country
United States
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20853
Country
United States
City
Flowood
State/Province
Mississippi
ZIP/Postal Code
39232
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45417
Country
United States
City
Portland
State/Province
Oregon
ZIP/Postal Code
97214
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
City
North Charleston
State/Province
South Carolina
ZIP/Postal Code
29405
Country
United States
City
Orem
State/Province
Utah
ZIP/Postal Code
84058
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Open-Label, Safety Study of Lofexidine
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