Renally Impaired SubjectsPhase 1NCT02313103
Single-dose Pharmacokinetics and Safety of Oral Lofexidine in Renally-Impaired Subjects
A Phase 1 study testing lofexidine HCl in people with Renally Impaired Subjects, 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 8 adult subjects with ESRD maintained on hemodialysis (3 times per week) and 8 control subjects with normal renal function, recruited as 1:1 matches to each ESRD subjects, matched for gender, age, and BMI. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Renally Impaired Subjects
- What is being tested?
- lofexidine HCl
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2014to Feb 2015
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Between ages of 18-75 years at enrollment with a BMI between 18 and 38 kg/m2, inclusive. Subjects with normal renal function: gender, age (±10 years), and BMI (±15%) matched to their ESRD subject.
- Male or female; however, if female: must be using contraception if of childbearing potential or must be surgically sterile; and must not be lactating.
- Subjects with ESRD must have been receiving adequate maintenance hemodialysis (at least 3 times per week) for at least 3 months before Day -1 (i.e., approximate Kt/V >1.1 based on subject's nephrologist and Investigator); subjects with normal renal function must have a creatinine clearance (CLcr) of less than or equal to 90 mL/min as estimated by Cockcroft and Gault or, if clinically indicated, by a 24 hour urine CLcr test.
- Subjects with ESRD must be on a stable medication program, except for medications prescribed for maintenance of hemoglobin, for at least 2 weeks before Day 1.
- At screening a matched control subject is in good health based on medical history, physical exam, laboratory profile, and ECG as judged by the Investigator.
- If subject smokes, subject agrees to limit smoking while in the study to not more than 10 cigarettes per day.
- Provides written informed consent before participation in the study, and an appropriate HIPAA (Health Insurance Portability and Accountability Act) form is signed and dated.
Who cannot join
- Fails to meet all of the inclusion criteria.
- 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 ESRD subject has a history of clinically significant disease including cardiovascular, GI, hepatic, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease.
- Females: pregnant, breastfeeding, planning to become pregnant, or a positive pregnancy test.
- Clinically significant illness other than renal disease or known conditions associated with renal disease for ESRD subjects, within 4 weeks before Day -1.
- Use of herbal supplements within 3 weeks before Day 1.
- Received treatment of more than a single dose of CYP3A4 inducer (e.g., rifampin, barbiturates, phenytoin, glucocorticoids, St. John's Wort) within 4 weeks before Day -1.
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- Received treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, diltiazem, macrolides antibiotics) within 2 weeks before Day -1.
- Currently taking any medication identified as potentially producing QTc prolongations of 10 msec or greater.
- Received an investigational medication during the last month (30 days) preceding Day -1.
- Consumes more than 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) or has a significant history of alcohol abuse or drug/chemical abuse within the last 1 year.
- Consumed grapefruit or grapefruit juice within 4 days before Day 1.
- Positive urine or saliva (ESRD subjects) drug screen and alcohol breathalyzer test, unless positive result is due to an approved prescribed medication (pain medication or benzodiazepine).
- Positive human immunodeficiency virus (HIV) test or tests positive for hepatitis B surface antigen.
- Known allergy or intolerance to any compound in the test product or any other closely related compound.
- Donated blood/plasma exceeding 500 mL, during the 3 month period before Day 1.
- Abnormal electrolyte values, including any including any pre-dialysis values in ESRD subjects outside of the following ranges: potassium 3.0-6.5 mmol/L; calcium 7.0-11.0 mg/dL; sodium: 120 150 mmol/L.
- Abnormal cardiovascular exam at Screening, including any of the following: clinically significant abnormal ECG at Screening (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; blood pressure >180/105 mmHg; or prior history of myocardial infarction within 1 year before Day 1.
- Subjects with normal renal function will not be eligible to participate in the study if any of the following exclusion criteria also apply: Received any over-the-counter medication, including topical medications, vitamins, and nutritional supplements or any prescription medication (except female hormonal contraceptives or hormone replacement therapy) within 14 days or 5 half lives (whichever is less) before Day 1.
- Subjects with ESRD will not be eligible to participate in the study if any of the following exclusion criteria also apply: Recipient of a functioning transplanted solid organ.
Trial locations and contacts
1 site in 1 country.
About this study
This is a phase 1, open-label, parallel-group, single-dose study of lofexidine in 8 adult subjects with ESRD maintained on hemodialysis (3 times per week) and 8 control subjects with normal renal function, recruited as 1:1 matches to each ESRD subjects, matched for gender, age, and BMI.
Read the detailed description
This is a Phase 1, open-label, parallel-group, single-dose study of lofexidine in 8 adult subjects with ESRD maintained on hemodialysis (3 times per week) and 8 control subjects with normal renal function (creatinine [Cr] clearance >90 mL/min), recruited as 1:1 matches to each ESRD subject, matched for gender, age (±10 years), and body mass index (BMI) (±15%). Normal renal function and ESRD subjects will be confined to an inpatient facility from the day before dosing to 144 or 156 hours after dosing, respectively, for a total of 7 8 nights and 8-9 days of inpatient confinement.
Subjects who successfully complete screening will report to the inpatient facility at an appropriate time the day before study drug administration to undergo pre-dosing study procedures (Day 1). The next morning (Day 1), all subjects will receive breakfast (approximately 6 hours before planned lofexidine dosing) and then ESRD subjects will begin their hemodialysis session. All subjects will receive a single, oral dose of 400 µg lofexidine HCl (two 200 µg tablets), dosed with 240 mL of water, the clock time for which will be approximately the same for both normal renal function subjects and ESRD subjects. Because ESRD subjects will be maintained on 3 times per week dialysis, lofexidine will be administered near the beginning of a 3-day between-dialysis interval.
Fingerprick blood samples for subjects with normal renal function will be collected for PK analysis at multiple time points over the next 144 hours. Fingerprick blood samples for ESRD subjects will be collected for PK analysis at multiple time points over the next 156 hours. Fingerprick blood samples (0.5 mL each) will be collected in BD Microtainer pink top K2EDTA tubes.
Two (2) venous blood samples (4-6 mL each in K2EDTA tubes) will be collected from each subject for lofexidine protein binding analysis, one sample collected 0-60 minutes before dosing and one sample collected 4 hours post-dose.
Pooled urine samples for subjects with normal renal function will be collected at 0 3 hours, 3 6 hours, 6 12 hours, 12 24 hours, 24 48 hours, 48 72 hours, 72 96 hours, and 96 144 hours post-dose. Pooled urine samples will be collected from ESRD subjects as available according to the same schedule.
Arterial and venous blood samples from the arterial-venous (A-V) shunt (0.5 mL in BD Microtainer pink top K2EDTA tubes) for PK analysis will be collected from ESRD subjects at 0.5, 1.5, 2.5, and 3.5 hours into each of the two 4 hour hemodialysis sessions. Additionally, fingerprick blood samples (0.5 mL) will be collected from the hand contralateral to the arm used for the dialysis A V shunt at each of these specified time points. Dialysate from ESRD subjects will be collected during the two 4 hour hemodialysis sessions at 0 1 hour, 1 2 hour, 2 3 hour, and 3 4 hour. Two 10 mL samples from each of the 1-hour pooled dialysate collections will be aliquoted into suitable collection tubes.
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
- Renally Impaired Subjects
- Being tested
- lofexidine HCl
- Keywords
- ESRD, End Stage Renal Disease, Normal Healthy Volunteers, Renally Impaired
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lofexidine HClDrug
400 micrograms
| Study group | Role | What they receive |
|---|---|---|
| Lofexidine HCl | Other | End Stage Renal Disease (ESRD) subjects will be dosed with 400 micrograms of lofexidine HCl with 240 mL water after their hemodialysis session. Receives: Drug: lofexidine HCl |
| Matched Control | Other | normal renal function subjects (enrolled to match each End Stage Renal Disease subject) will be dosed with 400 micrograms of lofexidine HCl with 240 mL water at the same clock time as ESRD subjects. Receives: Drug: lofexidine HCl |
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
Measured: pre dose until 156 hours post dose
Secondary outcomes (5)
Adverse events
Measured: screening through day 7 or 8
Clinical laboratory tests
hematology, chemistry and urinalysis
Measured: screening through day 7 or 8
Vital signs
blood pressure and pulse
Measured: screening through day 7 or 8
12-lead ECG
Measured: screening through day 7 or 8
holter ECG
Measured: screening through day 7 or 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2014 (estimated)
- Study startNov 2014
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renally Impaired SubjectsStudies 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 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, OCRSJames Longstreth, PhD, Study director, USWM, LLC (dba US WorldMeds)Charles Gorodetzky, MD, Study director, USWM, LLC (dba US WorldMeds)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02313103
- Sponsor's protocol ID
- USWM-LX1-1008
- Other IDs
- 1R01DA030916
- Status last verified
- Oct 2017
- First submitted
- 5 Dec 2014
- Last updated
- 26 Oct 2017
- Results posted
- No
- Data monitoring committee
- 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
- Single-dose Pharmacokinetics and Safety of Oral Lofexidine in Renally-Impaired Subjects
- ClinicalTrials.gov ID
- NCT02313103
- Acronym / sponsor ID
- USWM-LX1-1008
- Conditions
- Renally Impaired Subjects
- Keywords
- ESRD, End Stage Renal Disease, Normal Healthy Volunteers, Renally Impaired
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- USWM, LLC (dba US WorldMeds)Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Nov 2014
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 9 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 8 adult subjects with ESRD maintained on hemodialysis (3 times per week) and 8 control subjects with normal renal function, recruited as 1:1 matches to each ESRD subjects, matched for gender, age, and BMI.
Detailed description
This is a Phase 1, open-label, parallel-group, single-dose study of lofexidine in 8 adult subjects with ESRD maintained on hemodialysis (3 times per week) and 8 control subjects with normal renal function (creatinine [Cr] clearance >90 mL/min), recruited as 1:1 matches to each ESRD subject, matched for gender, age (±10 years), and body mass index (BMI) (±15%). Normal renal function and ESRD subjects will be confined to an inpatient facility from the day before dosing to 144 or 156 hours after dosing, respectively, for a total of 7 8 nights and 8-9 days of inpatient confinement.
Subjects who successfully complete screening will report to the inpatient facility at an appropriate time the day before study drug administration to undergo pre-dosing study procedures (Day 1). The next morning (Day 1), all subjects will receive breakfast (approximately 6 hours before planned lofexidine dosing) and then ESRD subjects will begin their hemodialysis session. All subjects will receive a single, oral dose of 400 µg lofexidine HCl (two 200 µg tablets), dosed with 240 mL of water, the clock time for which will be approximately the same for both normal renal function subjects and ESRD subjects. Because ESRD subjects will be maintained on 3 times per week dialysis, lofexidine will be administered near the beginning of a 3-day between-dialysis interval.
Fingerprick blood samples for subjects with normal renal function will be collected for PK analysis at multiple time points over the next 144 hours. Fingerprick blood samples for ESRD subjects will be collected for PK analysis at multiple time points over the next 156 hours. Fingerprick blood samples (0.5 mL each) will be collected in BD Microtainer pink top K2EDTA tubes.
Two (2) venous blood samples (4-6 mL each in K2EDTA tubes) will be collected from each subject for lofexidine protein binding analysis, one sample collected 0-60 minutes before dosing and one sample collected 4 hours post-dose.
Pooled urine samples for subjects with normal renal function will be collected at 0 3 hours, 3 6 hours, 6 12 hours, 12 24 hours, 24 48 hours, 48 72 hours, 72 96 hours, and 96 144 hours post-dose. Pooled urine samples will be collected from ESRD subjects as available according to the same schedule.
Arterial and venous blood samples from the arterial-venous (A-V) shunt (0.5 mL in BD Microtainer pink top K2EDTA tubes) for PK analysis will be collected from ESRD subjects at 0.5, 1.5, 2.5, and 3.5 hours into each of the two 4 hour hemodialysis sessions. Additionally, fingerprick blood samples (0.5 mL) will be collected from the hand contralateral to the arm used for the dialysis A V shunt at each of these specified time points. Dialysate from ESRD subjects will be collected during the two 4 hour hemodialysis sessions at 0 1 hour, 1 2 hour, 2 3 hour, and 3 4 hour. Two 10 mL samples from each of the 1-hour pooled dialysate collections will be aliquoted into suitable collection tubes.
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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lofexidine HCl | Other | Drug: lofexidine HClEnd Stage Renal Disease (ESRD) subjects will be dosed with 400 micrograms of lofexidine HCl with 240 mL water after their hemodialysis session. |
| Matched Control | Other | Drug: lofexidine HClnormal renal function subjects (enrolled to match each End Stage Renal Disease subject) will be dosed with 400 micrograms of lofexidine HCl with 240 mL water at the same clock time as ESRD subjects. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Between ages of 18-75 years at enrollment with a BMI between 18 and 38 kg/m2, inclusive. Subjects with normal renal function: gender, age (±10 years), and BMI (±15%) matched to their ESRD subject.
- Male or female; however, if female: must be using contraception if of childbearing potential or must be surgically sterile; and must not be lactating.
- Subjects with ESRD must have been receiving adequate maintenance hemodialysis (at least 3 times per week) for at least 3 months before Day -1 (i.e., approximate Kt/V >1.1 based on subject's nephrologist and Investigator); subjects with normal renal function must have a creatinine clearance (CLcr) of less than or equal to 90 mL/min as estimated by Cockcroft and Gault or, if clinically indicated, by a 24 hour urine CLcr test.
- Subjects with ESRD must be on a stable medication program, except for medications prescribed for maintenance of hemoglobin, for at least 2 weeks before Day 1.
- At screening a matched control subject is in good health based on medical history, physical exam, laboratory profile, and ECG as judged by the Investigator.
Key exclusion criteria (19 listed)
- Fails to meet all of the inclusion criteria.
- 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 ESRD subject has a history of clinically significant disease including cardiovascular, GI, hepatic, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease.
- Females: pregnant, breastfeeding, planning to become pregnant, or a positive pregnancy test.
- Clinically significant illness other than renal disease or known conditions associated with renal disease for ESRD subjects, within 4 weeks before Day -1.
- Use of herbal supplements within 3 weeks before Day 1.
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 HCl400 micrograms | Drug | Lofexidine HCl, Matched Control |
Primary outcome
PK Profile
Time frame: pre dose until 156 hours post dose
Cmax, Tmax, AUC, λz, CL/F, T½, CLr, CLd, Ae
5 secondary outcomes
Adverse events
Time frame: screening through day 7 or 8
Clinical laboratory tests
Time frame: screening through day 7 or 8
Vital signs
Time frame: screening through day 7 or 8
12-lead ECG
Time frame: screening through day 7 or 8
holter ECG
Time frame: screening through day 7 or 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.
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
OCRS
James Longstreth, PhD study director
USWM, LLC (dba US WorldMeds)
Charles Gorodetzky, MD 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 HCl in people with Renally Impaired Subjects, 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 19 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?
PK Profile (time frame: pre dose until 156 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 26 Oct 2017.