Efficacy, Safety and Dose-Response Study Followed by Open-Label Study of Lofexidine Treatment of Opioid Withdrawal
Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy, Safety, and Dose-Response Study of Lofexidine for Treatment of Opioid Withdrawal (Days 1-7) Followed by Open-Label, Variable Dose Lofexidine Treatment (Days 8-14)
2 other identifiers
interventional
603
1 country
18
Brief Summary
The purpose of this study is to look at the efficacy and safety for lofexidine hydrochloride, an alpha-2 adrenergic agonist under development for the treatment of acute withdrawal from short-acting opioids. The study takes place in 2 parts: a 7-day inpatient double-blind treatment portion where subjects will be randomly assigned to one of three doses of study medication (2.4 mg total daily dose of lofexidine, 3.2 mg total daily dose of lofexidine, or placebo) followed by an optional open-label treatment period where subjects will be inpatient or outpatient and receive lofexidine at variable dosing for up to an additional 7 days. The Investigator hypothesizes that subjects will achieve maximum treatment effect with tolerable side effects at the 3.2 mg total daily dose and that both the 3.2 mg and 2.4 total daily doses will show better efficacy over placebo in treating symptoms of acute opioid withdrawal.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2013
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 22, 2013
CompletedFirst Posted
Study publicly available on registry
May 27, 2013
CompletedStudy Start
First participant enrolled
June 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2014
CompletedResults Posted
Study results publicly available
February 4, 2021
CompletedMarch 22, 2022
February 1, 2022
1.4 years
May 22, 2013
November 25, 2020
March 11, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Difference Between the Overall Means From Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) Scores
The SOWS-Gossop was completed by the mITT population subject at baseline, once daily at 3.5 hours after the first dose of the study medication on Days 1 to 7. It consists of 10 items that are scored on a 4-point scale; 0=none, 1=mild, 2=moderate, and 3=severe. The overall score is the simple sum of the 10-item scores (minimum overall score of 0, maximum score of 30). Higher individual scores on the scale indicate greater symptom severity. However, as the outcome measure is a difference from placebo, a lower number indicates a better outcome. mITT population: all randomized subjects who received at least 1 dose of study medication
Days 1 through 7
Secondary Outcomes (1)
Completion Status
Day 7
Study Arms (4)
Lofexidine HCl (2.4mg dose)
ACTIVE COMPARATOR225 subjects will be randomized to receive 2.4 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 2.4 mg (one tablet in each dose will be a placebo tablet to maintain the blind) for up to 7 days.
Lofexidine HCl (3.2mg dose)
ACTIVE COMPARATOR225 subjects will be randomized to receive 3.2 mg total daily dose of lofexidine HCl during the double-blind period of the study. Subjects will take 4 tablets QID for a total daily dose of 3.2 mg for up to 7 days.
Placebo
PLACEBO COMPARATOR150 subjects will be randomized to receive placebo during the double-blind period of the study. Subjects will take 4 tablets QID for up to 7 days.
Open Label Lofexidine HCl
OTHERDuring the open-label portion of the study, subjects will be given the option to receive lofexidine HCl tablets for up to 7 days. Dosing regimens are at the discretion of the Investigator.
Interventions
Lofexidine HCl tablets will be available in 0.2 mg tablets. Lofexidine will be provided in total daily doses as indicated during the double blind portion of the study.
Lofexidine-matching tablets without the active pharmaceutical ingredient will be provided as 4 tablets QID during the double-blind portion of the study to subjects randomized to placebo.
Lofexidine HCl tablets will are available in 0.2 mg tablets. During the optional open-label portion of the study, Lofexidine HCl can be prescribed at the discretion of the Investigator but total daily dose will not exceed 3.2 mg.
Eligibility Criteria
You may qualify if:
- Male or female at least 18 years of age.
- Currently dependence, according to the Mini International Neuropsychiatric Interview (M.I.N.I.) \[17, 18\], on any opioid with a half-life similar to heroin or morphine, including Vicodin®, Lortab®, Lorcet®, Percocet®, Percodan®, Tylox®, or Hydrocodone (by any route of administration), or oxycodone (oxycodone and oxycodone time-released formulation when crushed and snorted, injected or swallowed after chewing).
- Seeking treatment for opioid dependence.
- Score of ≥2 on the Objective Opiate Withdrawal Scale (OOWS-Handelsman) at Baseline.
- Reported use of heroin, morphine, or any opioid with a half-life similar to heroin or morphine for at least 21 of the past 30 days.
- Urine toxicology screen positive for opioids but negative for methadone and buprenorphine.
- Females of childbearing potential must agree to using birth control methods and must have had documented proof.
- Able to verbalize understanding of the consent form, able to provide written informed consent, verbalize willingness to complete study procedures, and pass the study consent quiz with 100% accuracy (if necessary, quiz may be administered more than one time).
You may not qualify if:
- Female subject who is pregnant or lactating.
- Self-reported use of methadone or buprenorphine in the past 14 days.
- Serious medical illnesses including, but not limited to: seizures, pancreatic disease, liver disease, exposure to a hepatitis virus, and positive hepatitis results.
- Psychiatric disorder, based on the M.I.N.I., including but not limited to dementia or any disorder that, in the opinion of the study physician requires ongoing treatment that would make study participation unsafe or which would make treatment compliance difficult.
- 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.
- Abnormal cardiovascular exam at screening and before randomization, including any of the following: clinically significant abnormal electrocardiogram (ECG) (e.g., second or third degree heart block, uncontrolled arrhythmia, or QTcF interval greater than 450 msec for males and greater than 470 msec for females); heart rate less than 55 bpm or symptomatic bradycardia; systolic blood pressure (SBP) less than 95 mmHg or symptomatic hypotension; diastolic blood pressure (DBP) less than 65 mmHg; blood pressure (BP) greater than 155/95 mmHg; and prior history of myocardial infarction.
- Clinically significant abnormal laboratory values.
- Donated blood within the last 8 weeks.
- Participated in an investigational drug study within the past 3 months.
- Has "poor" veins that even a single venipuncture cannot be obtained during screening.
- Active tuberculosis (positive tuberculin test and/or confirmatory diagnostic chest x-ray).
- Active syphilis.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
Unknown Facility
Clovis, California, 93611, United States
Unknown Facility
Escondido, California, 92025, United States
Unknown Facility
San Diego, California, United States
Unknown Facility
Miami, Florida, 33136, United States
Unknown Facility
Orlando, Florida, 32806, United States
Unknown Facility
Atlanta, Georgia, 30308, United States
Unknown Facility
Oak Park, Illinois, 60301, United States
Unknown Facility
Lake Charles, Louisiana, 70629, United States
Unknown Facility
Baltimore, Maryland, 21229, United States
Unknown Facility
Flowood, Mississippi, United States
Unknown Facility
St Louis, Missouri, United States
Unknown Facility
Dayton, Ohio, United States
Unknown Facility
Mason, Ohio, 45050, United States
Unknown Facility
Austin, Texas, 78731, United States
Unknown Facility
Dallas, Texas, 75208, United States
Unknown Facility
DeSoto, Texas, 75115, United States
Unknown Facility
Orem, Utah, 84058, United States
Unknown Facility
Salt Lake City, Utah, 84106, United States
Related Publications (3)
Alam D, Tirado C, Pirner M, Clinch T. Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials. J Drug Assess. 2020 Jan 8;9(1):13-19. doi: 10.1080/21556660.2019.1704416. eCollection 2020.
PMID: 32002194DERIVEDDarpo B, Pirner M, Longstreth J, Ferber G. Effect of lofexidine on cardiac repolarization during treatment of opioid withdrawal. Drug Alcohol Depend. 2019 Dec 1;205:107596. doi: 10.1016/j.drugalcdep.2019.107596. Epub 2019 Sep 27.
PMID: 31606589DERIVEDFishman M, Tirado C, Alam D, Gullo K, Clinch T, Gorodetzky CW; CLEEN-SLATE Team. Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial. J Addict Med. 2019 May/Jun;13(3):169-176. doi: 10.1097/ADM.0000000000000474.
PMID: 30531234DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Affairs
- Organization
- USWM, LLC
Study Officials
- PRINCIPAL INVESTIGATOR
Charles W Gorodetzky, MD, PhD
US WorldMeds
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 22, 2013
First Posted
May 27, 2013
Study Start
June 1, 2013
Primary Completion
November 1, 2014
Study Completion
December 1, 2014
Last Updated
March 22, 2022
Results First Posted
February 4, 2021
Record last verified: 2022-02