HealthyPhase 1NCT01437306
Lofexidine Food Effect Study in Healthy Volunteers
A Phase 1 study testing Lofexidine HCl in people with Healthy, run by USWM, LLC (dba US WorldMeds) at 1 site in United States.
Trial summary
The objective of this single-dose, open-label, randomized, two-period, two-way crossover, food-effect study is to evaluate the effect of food on the rate of absorption and oral bioavailability of a test formulation of lofexidine 400 μg (2 x 200 μg tablet) manufactured by US WorldMeds, LLC. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Lofexidine HCl
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Oct 2011
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All subjects must satisfy the following criteria to be considered for study participation:
- Subject must be a male or non-pregnant, non-breastfeeding female.
- Subject must be between 18 and 50 years of age (inclusive).
- Subject's Body Mass Index (BMI) must be between 18 and 30 kg/m2 (inclusive), and subject must weigh a minimum of 50 kg (110 lbs).
- Female subjects must agree to use one of the following forms of birth control from screening until 14 days after completion of the study:
- Vasectomized partner (at least 6 months prior to dosing)
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- Post-menopausal (at least 2 years prior to dosing)
- Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) at least 6 months prior to dosing
- Double barrier (diaphragm with spermicide; condoms with spermicide)
- IUD (intrauterine device)
- Abstinence (must agree to use a double barrier method if they become sexually active during the study)
- Implanted or intrauterine hormonal contraceptives in use for at least 6 consecutive months prior to study dosing and throughout the study duration
- Oral, patch, and injected contraceptives or vaginal hormonal device (i.e. NuvaRing®) in use for at least 3 consecutive months prior to study dosing and throughout the study duration.
- Subject must voluntarily consent to participate in this study and provide their written informed consent prior to start of any study-specific procedures.
- Subject is willing and able to remain in the study unit for the entire duration of each confinement period.
- Subject is willing and able to consume the entire high-calorie, high-fat breakfast meal in the designated timeframe required during the assigned study period.
- Subject's vital signs must be within the following ranges to be included: Vital signs measured sitting after 3 minutes rest; heart rate: 40-90 bpm; systolic BP: 110-140 mmHg; diastolic BP: 60-90 mmHg. Out-of-range vital signs may be repeated once. Predose vital signs will be assessed by the Principal Investigator or designee (e.g., a medically qualified sub-investigator) prior to study drug administration. The Principal Investigator or designee will verify the eligibility of each subject with out-of-range vital signs and document approval prior to dosing.
Who cannot join
- History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
- Has a clinically significant abnormal finding on the physical exam, medical history, electrocardiogram (ECG), or clinical laboratory results at screening.
- History of any syncopal episode or seizures.
- Presence of acute disease state (eg, nausea, vomiting, fever, diarrhea) within 7 days prior to scheduled dose administration.
- History or presence of allergic or adverse response to lofexidine or related drugs.
- Has been on a significantly abnormal diet during the 4 weeks preceding the first dose of study medication.
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- Has donated blood or plasma within 30 days prior to the first dose of study medication.
- Has participated in another clinical trial (randomized subjects only) within 30 days prior to the first dose of study medication.
- Has used any over-the-counter (OTC) medication, including nutritional supplements, within 7 days prior to the first dose of study medication.
- Has used any prescription medication, except hormonal contraceptive or hormonal replacement therapy, within 14 days prior to the first dose of study medication.
- Subjects that have discontinued the use of implanted, intrauterine, or injected hormonal contraceptives must not have used any for 6 months prior to the first dose of study medication.
- Subjects that have discontinued the use of oral, patch, or vaginal hormonal contraceptives must not have used any for 1 month prior to the first dose of study medication.
- Has been treated with any known drugs that are moderate or strong inhibitors/inducers of CYP enzymes such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication and that in the Investigator's judgment may impact subject safety or the validity of the study results.
- Has smoked or used tobacco products within 60 days prior to the first dose of study medication.
- Has any prior history of substance abuse or treatment (including alcohol) within the past 2 years.
- Is a female with a positive pregnancy test result.
- Has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates).
- Has a positive test for Hepatitis B surface antigen, Hepatitis C antibody, or Human Immunodeficiency Virus (HIV) at screening or has been previously treated for Hepatitis B, Hepatitis C, or HIV infection.
- Has orthostatic hypotension at screening defined as a drop in systolic blood pressure ≥ 20 mmHg or a fall in diastolic blood pressure ≥ 10 mmHg following a 2 minute stand. Out-of-range vital signs may be repeated once. Predose vital signs will be assessed by the Principal Investigator or designee (e.g., a medically qualified sub-investigator) prior to study drug administration. The Principal Investigator or designee will verify the eligibility of each subject with out-of-range vital signs and document approval prior to dosing.
- Subjects with a QTcF greater than 450 msec (males) or greater than 470 msec (females), at screening obtained after 10 minutes rest in a supine position using the ECG machine algorithm.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-Dose, Open-Label, Randomized, Two-Way Crossover Food Effect Study of Lofexidine 400 μg (2 x 200 μg) Tablets
The objective of this single-dose, open-label, randomized, two-period, two-way crossover, food-effect study is to evaluate the effect of food on the rate of absorption and oral bioavailability of a test formulation of lofexidine 400 μg (2 x 200 μg tablet) manufactured by US WorldMeds, LLC.
Read the detailed description
This is a single-dose, open-label, randomized, two-period, two-way crossover, food-effect study in which 12 healthy adult subjects will receive two separate single-dose administrations of lofexidine 400 μg (2 x 200 μg tablet). In one study period, subjects will be administered the study treatment following an overnight fast of at least 10 hours. In the other study period subjects will fast overnight for at least 10 hours, then begin consuming an FDA standard high-calorie, high-fat breakfast meal 30 minutes prior to administration of the study drug.
Subjects will be assigned numbers in an ascending order, based on successful completion of the screening process.
Subjects will receive each of the treatments listed below in randomized fashion during the two treatment periods:
Treatment A: Test Formulation Lofexidine 400 μg Dose = 2 x 200 μg tablet administered under fasted conditions US WorldMeds, LLC
Treatment B: Test Formulation Lofexidine 400 μg Dose = 2 x 200 μg tablet administered under fed conditions US WorldMeds, LLC
Each drug administration will be separated by a washout period of at least seven days. Each dose will be orally administered along with 240 mL (8 fl. oz.) of room temperature tap water. After dosing, no food will be allowed until 4 hours post-dose. Except for the 240 mL of room temperature tap water provided with the dose, no water may be consumed for 1 hour prior through 1 hour post dose. Meals will be the same and scheduled at approximately the same times relative to dose for each study period.
In order to prevent adverse events (AEs) of hypotension, all subjects will have intravenous (IV) access established at each check-in and will be administered normal saline (NS) at a continuous rate of 150 cc/hour until 1 hour prior to each dose administration. The IV catheter will remain in place for at least 12 hours postdose so that additional fluid can be administered if needed. If symptoms or clinically significant hypotension persist, IV fluid administration may continue for more than 12 hours, until it is no longer needed as determined by the Investigator.
Subjects who withdraw from the study may be replaced. During each study period, 6 mL blood samples will be obtained prior to each dosing and following each dose at selected times through 48 hours post-dose. A total of 28 pharmacokinetic blood samples will be collected from each subject, 14 samples in each study period. Plasma pharmacokinetic samples will be analyzed for lofexidine using a validated analytical method. Appropriate pharmacokinetic parameters will be calculated for each formulation using non-compartmental methods. In addition, blood will be drawn and urine will be collected for clinical laboratory testing at screening and at the end of the study.
- Conditions
- Healthy
- Being tested
- Lofexidine HCl
- Keywords
- lofexidine, food effect, pharmacokinetics, healthy volunteer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lofexidine HClDrug
400 mcg (2 x 200 mcg tablets) administered orally as a single dose
| Study group | Role | What they receive |
|---|---|---|
| Lofexidine following overnight fast | Experimental | A single dose of lofexidine (400 mcg or 2 x 200 mcg tablets) will be given to subjects following a minimum 10 hour overnight fast. Receives: Drug: Lofexidine HCl |
| Lofexidine Following a High Fat Meal | Experimental | A single dose of lofexidine 400 mcg (or 2 x 200 mcg tablets) will be administered to subjects following a standard high-fat meal. Receives: Drug: Lofexidine HCl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparative Profile Pharmacokinetics TimeFrame 0.5, 1, 2, 3, 4, 5, 7, 10, 16, 24, 30, 36 and 48 hours post dose for Cmax, Tmax, Area Under the Curve, Elimination Rate Constant and Elimination Half Life
Samples will be analyzed for lofexidine concentration and calculations will be performed for the following: Cmax and Tmax will be taken directly from the data.
The elimination rate constant, will be calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve.
Elimination half-life (T½) as follows: T½ = ln(2) / λZ
Area under the curve will be calculated using the linear trapezoidal method and extrapolated to infinity using:
AUCinf = AUClast + Clast/ λZ where Clast is the final concentration LOQ.
Measured: 48 Hours Following Each Dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2011 (estimated)
- Study startOct 2011
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 13 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
- Charles W Gorodetzky, MD, PhD, Principal investigator, US WorldMedsJames A Longstreth, PhD, Principal investigator, US WorldMeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01437306
- Sponsor's protocol ID
- USWM-LX1-1004
- Other IDs
- 1R01DA030916-01
- Status last verified
- Feb 2018
- First submitted
- 13 Sep 2011
- 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
- A Single-Dose, Open-Label, Randomized, Two-Way Crossover Food Effect Study of Lofexidine 400 μg (2 x 200 μg) Tablets
- ClinicalTrials.gov ID
- NCT01437306
- Acronym / sponsor ID
- USWM-LX1-1004
- Conditions
- Healthy
- Keywords
- lofexidine, food effect, pharmacokinetics, healthy volunteer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- USWM, LLC (dba US WorldMeds)Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Oct 2011
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 20 Sep 2011 (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 objective of this single-dose, open-label, randomized, two-period, two-way crossover, food-effect study is to evaluate the effect of food on the rate of absorption and oral bioavailability of a test formulation of lofexidine 400 μg (2 x 200 μg tablet) manufactured by US WorldMeds, LLC.
Detailed description
This is a single-dose, open-label, randomized, two-period, two-way crossover, food-effect study in which 12 healthy adult subjects will receive two separate single-dose administrations of lofexidine 400 μg (2 x 200 μg tablet). In one study period, subjects will be administered the study treatment following an overnight fast of at least 10 hours. In the other study period subjects will fast overnight for at least 10 hours, then begin consuming an FDA standard high-calorie, high-fat breakfast meal 30 minutes prior to administration of the study drug.
Subjects will be assigned numbers in an ascending order, based on successful completion of the screening process.
Subjects will receive each of the treatments listed below in randomized fashion during the two treatment periods:
Treatment A: Test Formulation Lofexidine 400 μg Dose = 2 x 200 μg tablet administered under fasted conditions US WorldMeds, LLC
Treatment B: Test Formulation Lofexidine 400 μg Dose = 2 x 200 μg tablet administered under fed conditions US WorldMeds, LLC
Each drug administration will be separated by a washout period of at least seven days. Each dose will be orally administered along with 240 mL (8 fl. oz.) of room temperature tap water. After dosing, no food will be allowed until 4 hours post-dose. Except for the 240 mL of room temperature tap water provided with the dose, no water may be consumed for 1 hour prior through 1 hour post dose. Meals will be the same and scheduled at approximately the same times relative to dose for each study period.
In order to prevent adverse events (AEs) of hypotension, all subjects will have intravenous (IV) access established at each check-in and will be administered normal saline (NS) at a continuous rate of 150 cc/hour until 1 hour prior to each dose administration. The IV catheter will remain in place for at least 12 hours postdose so that additional fluid can be administered if needed. If symptoms or clinically significant hypotension persist, IV fluid administration may continue for more than 12 hours, until it is no longer needed as determined by the Investigator.
Subjects who withdraw from the study may be replaced. During each study period, 6 mL blood samples will be obtained prior to each dosing and following each dose at selected times through 48 hours post-dose. A total of 28 pharmacokinetic blood samples will be collected from each subject, 14 samples in each study period. Plasma pharmacokinetic samples will be analyzed for lofexidine using a validated analytical method. Appropriate pharmacokinetic parameters will be calculated for each formulation using non-compartmental methods. In addition, blood will be drawn and urine will be collected for clinical laboratory testing at screening and at the end of the study.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lofexidine following overnight fast | Experimental | Drug: Lofexidine HClA single dose of lofexidine (400 mcg or 2 x 200 mcg tablets) will be given to subjects following a minimum 10 hour overnight fast. |
| Lofexidine Following a High Fat Meal | Experimental | Drug: Lofexidine HClA single dose of lofexidine 400 mcg (or 2 x 200 mcg tablets) will be administered to subjects following a standard high-fat meal. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- All subjects must satisfy the following criteria to be considered for study participation:
- Female subjects must agree to use one of the following forms of birth control from screening until 14 days after completion of the study:
- Subject must voluntarily consent to participate in this study and provide their written informed consent prior to start of any study-specific procedures.
- Subject is willing and able to remain in the study unit for the entire duration of each confinement period.
- Subject is willing and able to consume the entire high-calorie, high-fat breakfast meal in the designated timeframe required during the assigned study period.
Key exclusion criteria (20 listed)
- History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
- Has a clinically significant abnormal finding on the physical exam, medical history, electrocardiogram (ECG), or clinical laboratory results at screening.
- History of any syncopal episode or seizures.
- Presence of acute disease state (eg, nausea, vomiting, fever, diarrhea) within 7 days prior to scheduled dose administration.
- History or presence of allergic or adverse response to lofexidine or related drugs.
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 mcg (2 x 200 mcg tablets) administered orally as a single dose | Drug | Lofexidine Following a High Fat Meal, Lofexidine following overnight fast |
Primary outcome
Comparative Profile Pharmacokinetics TimeFrame 0.5, 1, 2, 3, 4, 5, 7, 10, 16, 24, 30, 36 and 48 hours post dose for Cmax, Tmax, Area Under the Curve, Elimination Rate Constant and Elimination Half Life
Time frame: 48 Hours Following Each Dose
Samples will be analyzed for lofexidine concentration and calculations will be performed for the following: Cmax and Tmax will be taken directly from the data. The elimination rate constant, will be calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve. Elimination half-life (T½) as follows: T½ = ln(2) / λZ Area under the curve will be calculated using the linear trapezoidal method and extrapolated to infinity using: AUCinf = AUClast + Clast/ λZ where Clast is the final concentration LOQ.
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.
Charles W Gorodetzky, MD, PhD principal investigator
US WorldMeds
James A Longstreth, PhD principal investigator
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 Healthy, 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 17 inclusion and 20 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?
Comparative Profile Pharmacokinetics TimeFrame 0.5, 1, 2, 3, 4, 5, 7, 10, 16, 24, 30, 36 and 48 hours post dose for Cmax, Tmax, Area Under the Curve, Elimination Rate Constant and Elimination Half Life (time frame: 48 Hours Following Each 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.