Substance Withdrawal SyndromePhase 1NCT02801357
Study to Evaluate the Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction
A Phase 1 study testing lofexidine administration in subjects seeking buprenorphine dose reduction in people with Substance Withdrawal Syndrome and Opiate Addiction, run by USWM, LLC (dba US WorldMeds) at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the relative exposures of lofexidine and its major metabolites in subjects seeking buprenorphine dose reduction. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Substance Withdrawal Syndrome, Opiate Addiction, Opiate Dependence
- What is being tested?
- lofexidine administration in subjects seeking buprenorphine dose reduction
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to Aug 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Study to Evaluate the Relative Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction
The purpose of this study is to evaluate the relative exposures of lofexidine and its major metabolites in subjects seeking buprenorphine dose reduction.
Read the 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.
- Being tested
- lofexidine administration in subjects seeking buprenorphine dose reduction
- Keywords
- substance withdrawal syndrome, opiate addiction, opiate dependence, opioid withdrawal syndrome, buprenorphine
- Medical subject headings
- Substance Withdrawal Syndrome, Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lofexidine administration in subjects seeking buprenorphine dose reductionDrug
| Study group | Role | What they receive |
|---|---|---|
| lofexidine with tapering buprenorphine | Experimental | 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. Receives: Drug: lofexidine administration in subjects seeking buprenorphine dose reduction |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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 outcomes (12)
Modified Clinical Global Impression - subject and observer
Measured: 3.5 hours post-8 AM dose on Days 1-7
Visual Analog Scale for Efficacy
Measured: 3.5 hours post-8 AM dose on Days 1-7
Columbia Suicide Severity Rating Scale (C-SSRS)
Measured: Baseline: Day -1; 3.5 hours post-first dose on Day 1; Day 8
Holter ECGs
Measured: Day -1; pre-1 PM dose, 3 and 4 hours post-1 PM dose on Days 1 and 6
Blood pressure and pulse (sitting and standing)
Measured: screening; Day -1; within 30 minutes before every dose Days 1-8
Laboratory Assessments
Measurements in hematology, chemistry, urinalysis, infectious disease panel. Labs will be done at screening.
Measured: screening
Oral temperature and respiration
Measured: screening; Day -1; pre-8 AM dose on Days 1-8
12-Lead ECG
Measured: screening
Adverse Events Assessment
Measured: Day -1; Days 1-8
Urine drug screening
Measured: Screening; Day -1, Days 1-8
Concomitant medications
Measured: Screening; Day -1, Days 1-8
Physical exam
Measured: screening; Day -1; Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2016 (estimated)
- Study startJun 2016
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Substance Withdrawal SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- USWM, LLC (dba US WorldMeds)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02801357
- Sponsor's protocol ID
- USWM- LX1-1013
- Status last verified
- Oct 2017
- First submitted
- 10 Jun 2016
- Last updated
- 26 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study to Evaluate the Relative Exposures of Lofexidine and Its Major Metabolites in Subjects Seeking Buprenorphine Dose Reduction
- ClinicalTrials.gov ID
- NCT02801357
- Acronym / sponsor ID
- USWM- LX1-1013
- Keywords
- substance withdrawal syndrome, opiate addiction, opiate dependence, opioid withdrawal syndrome, buprenorphine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- USWM, LLC (dba US WorldMeds)Industry (pharma, biotech, devices)
- Study start
- Jun 2016
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 15 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the relative exposures of lofexidine and its major metabolites in subjects seeking buprenorphine dose reduction.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| lofexidine with tapering buprenorphine | Experimental | Drug: lofexidine administration in subjects seeking buprenorphine dose reductionEnrolled 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. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lofexidine administration in subjects seeking buprenorphine dose reduction | Drug | lofexidine with tapering buprenorphine |
Primary outcome
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
12 secondary outcomes
Modified Clinical Global Impression - subject and observer
Time frame: 3.5 hours post-8 AM dose on Days 1-7
Visual Analog Scale for Efficacy
Time frame: 3.5 hours post-8 AM dose on Days 1-7
Columbia Suicide Severity Rating Scale (C-SSRS)
Time frame: Baseline: Day -1; 3.5 hours post-first dose on Day 1; Day 8
Holter ECGs
Time frame: Day -1; pre-1 PM dose, 3 and 4 hours post-1 PM dose on Days 1 and 6
Blood pressure and pulse (sitting and standing)
Time frame: screening; Day -1; within 30 minutes before every dose Days 1-8
Laboratory Assessments
Time frame: screening
Oral temperature and respiration
Time frame: screening; Day -1; pre-8 AM dose on Days 1-8
12-Lead ECG
Time frame: screening
Adverse Events Assessment
Time frame: Day -1; Days 1-8
Urine drug screening
Time frame: Screening; Day -1, Days 1-8
Concomitant medications
Time frame: Screening; Day -1, Days 1-8
Physical exam
Time frame: screening; Day -1; Day 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing lofexidine administration in subjects seeking buprenorphine dose reduction in people with Substance Withdrawal Syndrome and Opiate Addiction, run by USWM, LLC (dba US WorldMeds) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2017.