Clinical trial NCT02363998: Open-Label, Safety Study of Lofexidine
Official title: A Phase 3, Open-Label, Safety Study of Lofexidine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Opioid Withdrawal
Keywords: detoxification
agonist taper
methadone step down
buprenorphine step down
opioid withdrawal syndrome
Lead sponsor: USWM, LLC (dba US WorldMeds)
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2015-02-16
Enrollment: 286
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Occurrence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Days 1-14
measure: Overall Occurrence of Serious Treatment Emergent Adverse Events (Serious TEAEs)
timeFrame: Days 1-14
measure: Overall Treatment Emergent Adverse Events (TEAEs) by Severity
timeFrame: Days 1-14
measure: Occurrence of Per Protocol Adverse Events of Special Interest (AESI)
timeFrame: Day 1 to Day 14
measure: Occurrence of Adverse Events (AEs) Not Related to Opioid Withdrawal
timeFrame: Day 1 to Day 14
measure: Mean Observed and Change From Screening in Seated Systolic Blood Pressure (mmHg): Vital Sign
timeFrame: Day 1 to Day 14
measure: Mean Observed and Change From Screening in Standing Systolic Blood Pressure (mmHg): Vital Sign
timeFrame: Day 1 to Day 14
measure: Mean Observed and Change From Screening in Seated Diastolic Blood Pressure (mmHg): Vital Sign
timeFrame: Day 1 to Day 14
measure: Mean Observed and Change From Screening in Standing Diastolic Blood Pressure (mmHg): Vital Sign
timeFrame: Day 1 to Day 14
measure: Mean Observed and Change From Screening in Seated Pulse (Bpm): Vital Signs
timeFrame: Day 1 to Day 14
measure: Mean Observed and Change From Screening in Standing Pulse (Bpm): Vital Signs
timeFrame: Day 1 to Day 14
measure: Columbia Suicide Severity Rating Scale Questionnaire (C-SSRS): Suicidal Ideation and Behavior Numbers
timeFrame: Day 1 to Day 14
measure: Clinical Laboratory Test Change From Baseline: Hematology
timeFrame: Day 1 to Day 14
measure: Clinical Laboratory Test Change From Baseline: Chemistry
timeFrame: Day 1 to Day 14
measure: Clinical Laboratory Test Change From Baseline: Urinalysis
timeFrame: Day 1 to Day 7
measure: Safety Electrocardiograms (ECG) Evaluation Shift From Baseline to Post Dose and End of Study
timeFrame: Day 1 and Day 14
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Springdale
country: United States
state: Arkansas
city: San Diego
country: United States
state: California
city: Fort Lauderdale
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Winfield
country: United States
state: Illinois
city: Lake Charles
country: United States
state: Louisiana
city: Rockville
country: United States
state: Maryland
city: Flowood
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Dayton
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Pittsburgh
country: United States
state: Pennsylvania
city: North Charleston
country: United States
state: South Carolina
city: Orem
country: United States
state: Utah
Study officials:
affiliation: US WorldMeds
name: Charles W Gorodetzky, MD, PhD
role: STUDY_DIRECTOR
References: