Liver FailurePhase 1NCT02318836
Single-Dose Pharmacokinetics and Safety of Oral Lofexidine in Hepatically-Impaired Subjects
A Phase 1 study testing Lofexidine Hydrochloride (HCl) tablets in people with Liver Failure, run by USWM, LLC (dba US WorldMeds) at 1 site in United States.
Trial summary
This is a Phase 1, open-label, parallel-group, single-dose study of lofexidine in 6 adult subjects with mild hepatic impairment (Child Pugh score of 5 6), 6 adult subjects with moderate hepatic impairment (Child Pugh score 7 9), 6 adult subjects with severe hepatic impairment (Child Pugh score 10 15), and 6 control… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Liver Failure
- What is being tested?
- Lofexidine Hydrochloride (HCl) tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to Oct 2014
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Site will evaluate each subject for criteria in detail, which will include:
- Between ages of 18 to 65 years at enrollment with a BMI between 19 and 38 kg/m2, inclusive.
- Subject is eligible to enter the study if:
- Matched control subject: normal hepatic function and free from other clinically significant illnesses or disease, and medical history, physical examination, laboratory results, and other tests consistent with health, as determined by the Investigator.
- Subject with mild hepatic impairment: Child-Pugh hepatic dysfunction staging system score of 5-6 Points (Stage A) and medical history, physical examination, laboratory results, and other tests consistent with their hepatic impairment, as determined by the Investigator.
- Subject with moderate hepatic impairment: Child-Pugh hepatic dysfunction staging system score of 7 9 Points (Stage B) and medical history, physical examination, laboratory results, and other tests consistent with their hepatic impairment, as determined by the Investigator.
- Subject with severe hepatic impairment: Child-Pugh hepatic dysfunction staging system score of 10-15 Points (Stage C) and medical history, physical examination, laboratory results, and other tests consistent with their hepatic impairment, as determined by the Investigator.
Who cannot join
- Site will evaluate each subject for criteria in detail, which will include:
- The matched control subject has a history of clinically significant disease, including cardiovascular, gastrointestinal (GI), renal, hepatic, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease or the hepatically-impaired subject has a history of clinically significant disease including cardiovascular, GI, renal, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease.
- Abnormal cardiovascular exam at Screening, including any of the following:
- clinically significant abnormal ECG (e.g., second or third degree heart block, uncontrolled arrhythmia, QTcF (Fridericia's correction) interval >450 msec for males and >470 msec for females).
- heart rate <45 bpm or symptomatic bradycardia;
- systolic blood pressure <90 mmHg or symptomatic hypotension;
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- blood pressure >160/100 mmHg; or
- prior history of myocardial infarction.
- Subjects with hepatic impairment will not be eligible to participate in the study if any of the following exclusion criteria also apply:
- Significant bleeding diathesis or esophageal bleeding within the last 8 weeks.
- Evidence of hepatic function deterioration within the last 4 weeks as indicated by liver transaminases, alkaline phosphatase, and gamma-glutamyl transpeptidase or a ≥50% worsening of serum bilirubin or prothrombin time.
- History of surgical portosystemic shunt.
- Prothrombin time >18 seconds.
Trial locations and contacts
1 site in 1 country.
United States1 site
Orlando Clinical Research Center
Orlando, Florida, 32809
About this study
This is a Phase 1, open-label, parallel-group, single-dose study of lofexidine in 6 adult subjects with mild hepatic impairment (Child Pugh score of 5 6), 6 adult subjects with moderate hepatic impairment (Child Pugh score 7 9), 6 adult subjects with severe hepatic impairment (Child Pugh score 10 15), and 6 control subjects with normal hepatic function with mean age, body mass index (BMI), and gender distribution targeted to be similar to the impaired hepatic function cohorts.
Read the detailed description
This is a Phase 1, open-label, parallel-group, single-dose study of lofexidine in 6 adult subjects with mild hepatic impairment (Child Pugh score of 5 6), 6 adult subjects with moderate hepatic impairment (Child Pugh score 7 9), 6 adult subjects with severe hepatic impairment (Child Pugh score 10 15), and 6 control subjects with normal hepatic function with mean age, body mass index (BMI), and gender distribution targeted to be similar to the impaired hepatic function cohorts. Subjects will be confined to an inpatient facility from the evening before dosing to 144 hours after dosing.
Subjects who successfully complete screening will report to the inpatient facility at an appropriate time the evening before study drug administration (Day 1) to ensure a minimum 10 hour fast. The next morning (Day 1) while still fasting, subjects will receive a single, oral dose of 400 µg lofexidine HCl (two 200 µg tablets). Blood samples will be collected for pharmacokinetic (PK) analysis at multiple time points over the next 144 hours (Day 7). Pooled urine samples will be collected at 0 3 hours, 3 6 hours, 6 12 hours, 12 24 hours, 24 48 hours, 48 96 hours, 96 120 hours and 120 144 hours post-dose. Safety will be assessed by recording adverse events (AEs), measuring vital signs (blood pressure and pulse rate) and clinical laboratory tests (chemistry, hematology, and urinalysis), recording 12 lead safety and Holter electrocardiograms (ECGs), and performing physical exams.
- Conditions
- Liver Failure
- Being tested
- Lofexidine Hydrochloride (HCl) tablets
- Keywords
- hepatic, hepatic impairment, lofexidine
- Medical subject headings
- Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lofexidine Hydrochloride (HCl) tabletsDrug
Lofexidine HCl tablets (two 200 µg tablets) will be administered orally with 240 mL room temperature tap water as a single 400 µg dose in the morning on Day 1 after a 10 hour overnight fast.
| Study group | Role | What they receive |
|---|---|---|
| Normal Hepatic function | Active comparator | Not described Receives: Drug: Lofexidine Hydrochloride (HCl) tablets |
| Mild Hepatic Impairment | Active comparator | (Child-Pugh score 5-6) Receives: Drug: Lofexidine Hydrochloride (HCl) tablets |
| Moderate Hepatic Impairment | Active comparator | (Child-Pugh score 7-9) Receives: Drug: Lofexidine Hydrochloride (HCl) tablets |
| Severe Hepatic Impairment | Active comparator | (Child-Pugh score 10-15) Receives: Drug: Lofexidine Hydrochloride (HCl) tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK Profile: Cmax, Tmax, AUC, λz, CL/F, T½, CLr, CLd, Ae
Cmax, Tmax, AUC, λz, CL/F, T½, CLr, CLd, Ae
Measured: pre dose until 144 hours post-dose
Secondary outcomes (5)
Adverse events
Measured: screening through day 7
Clinical laboratory tests
hematology, chemistry, urinalysis
Measured: screening through day 7
Vital signs
blood pressure and pulse
Measured: screening through day 7
12-lead ECG
Measured: screening through day 7
Holter ECG
Measured: pre dose through 8 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2014 (estimated)
- Study startJun 2014
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver FailureStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- USWM, LLC (dba US WorldMeds)
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Thomas Marbury, MD, Principal investigator, Orlando Clinical Research CenterJames Longstreth, PhD, Study director, USWM, LLC (dba US WorldMeds)Charles Gorodetzky, MD, PhD, Study director, USWM, LLC (dba US WorldMeds)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02318836
- Sponsor's protocol ID
- USWM-LX1-1007
- Other IDs
- 1R01DA030916
- Status last verified
- Feb 2018
- First submitted
- 29 Jul 2014
- Last updated
- 23 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-Dose Pharmacokinetics and Safety of Oral Lofexidine in Hepatically-Impaired Subjects
- ClinicalTrials.gov ID
- NCT02318836
- Acronym / sponsor ID
- USWM-LX1-1007
- Conditions
- Liver Failure
- Keywords
- hepatic, hepatic impairment, lofexidine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- USWM, LLC (dba US WorldMeds)Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Jun 2014
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 17 Dec 2014 (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.
This is a Phase 1, open-label, parallel-group, single-dose study of lofexidine in 6 adult subjects with mild hepatic impairment (Child Pugh score of 5 6), 6 adult subjects with moderate hepatic impairment (Child Pugh score 7 9), 6 adult subjects with severe hepatic impairment (Child Pugh score 10 15), and 6 control subjects with normal hepatic function with mean age, body mass index (BMI), and gender distribution targeted to be similar to the impaired hepatic function cohorts.
Detailed description
This is a Phase 1, open-label, parallel-group, single-dose study of lofexidine in 6 adult subjects with mild hepatic impairment (Child Pugh score of 5 6), 6 adult subjects with moderate hepatic impairment (Child Pugh score 7 9), 6 adult subjects with severe hepatic impairment (Child Pugh score 10 15), and 6 control subjects with normal hepatic function with mean age, body mass index (BMI), and gender distribution targeted to be similar to the impaired hepatic function cohorts. Subjects will be confined to an inpatient facility from the evening before dosing to 144 hours after dosing.
Subjects who successfully complete screening will report to the inpatient facility at an appropriate time the evening before study drug administration (Day 1) to ensure a minimum 10 hour fast. The next morning (Day 1) while still fasting, subjects will receive a single, oral dose of 400 µg lofexidine HCl (two 200 µg tablets). Blood samples will be collected for pharmacokinetic (PK) analysis at multiple time points over the next 144 hours (Day 7). Pooled urine samples will be collected at 0 3 hours, 3 6 hours, 6 12 hours, 12 24 hours, 24 48 hours, 48 96 hours, 96 120 hours and 120 144 hours post-dose. Safety will be assessed by recording adverse events (AEs), measuring vital signs (blood pressure and pulse rate) and clinical laboratory tests (chemistry, hematology, and urinalysis), recording 12 lead safety and Holter electrocardiograms (ECGs), and performing physical exams.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Normal Hepatic function | Active comparator | Drug: Lofexidine Hydrochloride (HCl) tablets |
| Mild Hepatic Impairment | Active comparator | Drug: Lofexidine Hydrochloride (HCl) tablets(Child-Pugh score 5-6) |
| Moderate Hepatic Impairment | Active comparator | Drug: Lofexidine Hydrochloride (HCl) tablets(Child-Pugh score 7-9) |
| Severe Hepatic Impairment | Active comparator | Drug: Lofexidine Hydrochloride (HCl) tablets(Child-Pugh score 10-15) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Between ages of 18 to 65 years at enrollment with a BMI between 19 and 38 kg/m2, inclusive.
- Subject is eligible to enter the study if:
Key exclusion criteria (13 listed)
- The matched control subject has a history of clinically significant disease, including cardiovascular, gastrointestinal (GI), renal, hepatic, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease or the hepatically-impaired subject has a history of clinically significant disease including cardiovascular, GI, renal, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease.
- Abnormal cardiovascular exam at Screening, including any of the following:
- Subjects with hepatic impairment will not be eligible to participate in the study if any of the following exclusion criteria also apply:
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 Hydrochloride (HCl) tabletsLofexidine HCl tablets (two 200 µg tablets) will be administered orally with 240 mL room temperature tap water as a single 400 µg dose in the morning on Day 1 after a 10 hour overnight fast. | Drug | Mild Hepatic Impairment, Moderate Hepatic Impairment, Normal Hepatic function, Severe Hepatic Impairment |
Primary outcome
PK Profile: Cmax, Tmax, AUC, λz, CL/F, T½, CLr, CLd, Ae
Time frame: pre dose until 144 hours post-dose
Cmax, Tmax, AUC, λz, CL/F, T½, CLr, CLd, Ae
5 secondary outcomes
Adverse events
Time frame: screening through day 7
Clinical laboratory tests
Time frame: screening through day 7
Vital signs
Time frame: screening through day 7
12-lead ECG
Time frame: screening through day 7
Holter ECG
Time frame: pre dose through 8 hours post dose
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 23 Feb 2018.
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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.
Thomas Marbury, MD principal investigator
Orlando Clinical Research Center
James Longstreth, PhD study director
USWM, LLC (dba US WorldMeds)
Charles Gorodetzky, MD, PhD study director
USWM, LLC (dba US WorldMeds)
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 Hydrochloride (HCl) tablets in people with Liver Failure, 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 7 inclusion and 13 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 23 Feb 2018. 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?
PK Profile: Cmax, Tmax, AUC, λz, CL/F, T½, CLr, CLd, Ae (time frame: pre dose until 144 hours post-dose). 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 23 Feb 2018.