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Trial record 90 of 79996 for:    subjects

Study to Evaluate the Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction

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ClinicalTrials.gov Identifier: NCT02801357
Recruitment Status : Completed
First Posted : June 15, 2016
Last Update Posted : October 26, 2017
Sponsor:
Information provided by (Responsible Party):
US WorldMeds LLC

Brief Summary:
The purpose of this study is to evaluate the relative exposures of lofexidine and its major metabolites in subjects seeking buprenorphine dose reduction.

Condition or disease Intervention/treatment Phase
Substance Withdrawal Syndrome Opiate Addiction Opiate Dependence Drug: lofexidine administration in subjects seeking buprenorphine dose reduction Phase 1

Detailed Description:
This is a Phase 1, open-label, inpatient study in male and female subjects seeking at least a 4 mg reduction of their buprenorphine maintenance dose. The purpose of this study is to assess the relative exposures of lofexidine and its 3 major metabolites in subjects tapering from buprenorphine maintenance treatment. Lofexidine is an alpha-2 adrenergic agonist under development for the treatment of acute withdrawal from short-acting opioids.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study to Evaluate the Relative Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction
Study Start Date : June 2016
Actual Primary Completion Date : August 2016
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: lofexidine with tapering buprenorphine
Enrolled subjects must be on a daily dose of between 8 - 24 mg of buprenorphine for at least 30 days. Once enrolled, subjects will receive lofexidine as follows: Days 1 through 3, 0.6 mg 4 times daily (QID; 2.4 mg daily); Days 4 through 6, 0.8 mg QID (3.2 mg daily), and Day 7 0.8 mg at 8 AM. Subjects will take their scheduled lofexidine doses at approximately 8 AM, 1 PM, 6 PM and 11 PM. Subjects will also reduce their current buprenorphine dose by at least 4 mg on Day 1.
Drug: lofexidine administration in subjects seeking buprenorphine dose reduction



Primary Outcome Measures :
  1. Predose and peak metabolite (N-[2- aminoethyl-2-[2,6-dichlorophenoxy] propanamide [LADP], 2-[2,6-dichlorophenoxy] propionic acid [LDPA] and 2,6-Dichlorophenol [2,6-DCP]) plasma concentration to lofexidine (parent) ratios on each day of treatment [ Time Frame: pre-1 PM dose and 3 hours post-1 PM dose on Days 1-6; pre-8 AM dose and 1, 3, 7, 12, 24, and 34 hours post-8 AM dose on Day 7 ]

Secondary Outcome Measures :
  1. Modified Clinical Global Impression - subject and observer [ Time Frame: 3.5 hours post-8 AM dose on Days 1-7 ]
  2. Visual Analog Scale for Efficacy [ Time Frame: 3.5 hours post-8 AM dose on Days 1-7 ]
  3. Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline: Day -1; 3.5 hours post-first dose on Day 1; Day 8 ]
  4. Holter ECGs [ Time Frame: Day -1; pre-1 PM dose, 3 and 4 hours post-1 PM dose on Days 1 and 6 ]
  5. Blood pressure and pulse (sitting and standing) [ Time Frame: screening; Day -1; within 30 minutes before every dose Days 1-8 ]
  6. Laboratory Assessments [ Time Frame: screening ]
    Measurements in hematology, chemistry, urinalysis, infectious disease panel. Labs will be done at screening.

  7. Oral temperature and respiration [ Time Frame: screening; Day -1; pre-8 AM dose on Days 1-8 ]
  8. 12-Lead ECG [ Time Frame: screening ]
  9. Adverse Events Assessment [ Time Frame: Day -1; Days 1-8 ]
  10. Urine drug screening [ Time Frame: Screening; Day -1, Days 1-8 ]
  11. Concomitant medications [ Time Frame: Screening; Day -1, Days 1-8 ]
  12. Physical exam [ Time Frame: screening; Day -1; Day 8 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have current dependency such that the subject is maintained on a daily dose between 8 and 24 mg of buprenorphine and is seeking reduction of their buprenorphine dose by at least 4 mg.
  • Urine toxicology screen positive for buprenorphine at Screening.
  • Agree to collection of blood samples for genotyping of CYP2D6 metabolizer status.
  • If female and of childbearing potential, subject must have been using birth control for at least 30 days and must agree to use an acceptable form of birth control through at least 30 days after the last dose of study drug.
  • If male, must agree to use an acceptable form of birth control throughout the entire study period and for 90 days after the last dose of study drug. Must not donate sperm for 90 days after the last dose of study drug.

Exclusion Criteria:

  • Be a female subject who is pregnant or lactating.
  • Have a very serious medical illness not under control.
  • Have participated in an investigational drug study within the past 30 days.
  • Received any drugs that are known strong, moderate or weak inhibitors of cytochrome P450 (CYP) enzymes CYP1A2, CYP2C19, or CYP2D6, within 14 days or 5 half-lives (whichever is more) before Day -1.
  • Abnormal cardiovascular exam at Screening.
  • Subjects requiring the following will be excluded: Tricyclic antidepressants, which may reduce the efficacy of imidazoline derivatives; Beta-receptor blockers, to avoid the risk of excessive bradycardia.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02801357


Locations
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United States, Kansas
Overland Park, Kansas, United States, 66212
Sponsors and Collaborators
US WorldMeds LLC

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Responsible Party: US WorldMeds LLC
ClinicalTrials.gov Identifier: NCT02801357     History of Changes
Other Study ID Numbers: USWM- LX1-1013
First Posted: June 15, 2016    Key Record Dates
Last Update Posted: October 26, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by US WorldMeds LLC:
substance withdrawal syndrome
opiate addiction
opiate dependence
opioid withdrawal syndrome
buprenorphine

Additional relevant MeSH terms:
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Syndrome
Behavior, Addictive
Opioid-Related Disorders
Substance Withdrawal Syndrome
Disease
Pathologic Processes
Compulsive Behavior
Impulsive Behavior
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Buprenorphine
Lofexidine
Clonidine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists
Antihypertensive Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Sympatholytics