A Study Evaluating the Relative Bioavailability of Lofexidine Granules for Reconstitution Compared to LUCEMYRA (Lofexidine) Tablets and the Effect of Food on the Bioavailability of the Lofexidine Granules for Reconstitution
Condition: Normal Healthy Volunteers
Intervention: Lofexidine (granules for reconstitution); LUCEMYRA (lofexidine) tablets
Intervention description: All subjects will be administered one 0.36 mg dose of lofexidine granules for reconstitution.; All subjects will be administered one 0.36 mg dose of LUCEMYRA (lofexidine) tablets.
Intervention MeSH terms: Lofexidine; Clonidine
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this open-label, single-dose, randomized, three-treatment, three-period,
      four-sequence, crossover study is to evaluate the relative bioavailability of a test
      formulation of lofexidine granules for reconstitution (oral) and LUCEMYRA tablets under
      fasted conditions and to evaluate the effect of food on the relative bioavailability of
      lofexidine granules for reconstitution (oral) when administered under fed compared to fasted
      conditions.
    

Eligibility criteria:

        Inclusion Criteria

          1. Males and females, 18-50 years of age, inclusive, with a Body Mass Index (BMI) of
             20.0-35.0 kg/m², inclusive.

          2. Female subjects must meet at least one of the following criterion:

               -  Agree to abstain from sexual intercourse from screening and throughout the
                  duration of the study.

               -  Have used and agree to continue to use a reliable method of contraception (e.g.,
                  condom with spermicide, IUD, hormonal contraceptives) for at least 30 days before
                  initial dosing and throughout the duration of the study.

               -  Surgically sterile (bilateral oophorectomy or hysterectomy, bilateral tubal
                  ligation or Essure® device placement at least 3 months prior to initial dosing).

               -  At least 1 year postmenopausal and have a documented FSH level ≥ 40 mIU/mL at
                  screening.

          3. Good health as determined by lack of clinically significant abnormalities in health
             assessments performed at screening.

          4. Signed and dated informed consent form, which meets all criteria of current FDA
             regulations.

        Exclusion Criteria

          1. Females who are pregnant, lactating, or likely to become pregnant during the study.

          2. History of allergy or sensitivity to lofexidine or any component of the study drug or
             history of any drug hypersensitivity or intolerance which, in the opinion of the
             Investigator, would compromise the safety of the subject or the study.

          3. Significant history or current evidence of chronic infectious disease, system
             disorders, or organ dysfunction, especially cardiovascular disorders (e.g., severe
             coronary insufficiency, recent myocardial infarction [within 1 year before initial
             dosing], cerebrovascular disease), respiratory disorders, congenital long QT syndrome,
             diabetes, hepatic or renal disorders (e.g., chronic renal failure).

          4. Pulse < 50 bpm or symptomatic bradycardia, as determined by the Investigator.

          5. Clinically significant history of hypotension, as determined by the Investigator, or
             has a sitting/supine systolic blood pressure < 90 mmHg and/or diastolic blood pressure
             < 60 mmHg, or hypertension, as determined by the Investigator, or has sitting/supine
             systolic blood pressure > 190 mmHg and/or diastolic > 95 mmHg; determined at
             screening.

          6. Experiences reduction of systolic blood pressure of at least 20 mmHg or diastolic
             blood pressure of at least 10 mmHg within 3 minutes of standing from a resting
             (sitting or supine) position; determined at screening.

          7. 12-lead ECG, conducted in triplicate, considered by the Investigator to be clinically
             significant (e.g., second or third degree heart block, uncontrolled arrhythmia) or has
             a QTcF (Fridericia's correction) interval > 440 msec in 2 of the 3 ECGs performed;
             determined at screening.

          8. Clinically significant history or presence of any gastrointestinal disease or history
             of malabsorption within the last year, as determined by the Investigator.

          9. History of any psychiatric disorders occurring within the last two years that required
             the subject to be hospitalized or treated with medication.

         10. Subject has history of suicidality based on responses provided on the Columbia-Suicide
             Severity Rating Scale (C-SSRS), or is at risk for self-harm or harm to others based on
             clinical interview, at the discretion of the Investigator.

         11. Ingestion of grapefruit-containing food or beverages (e.g., Fresca®) within 7 days
             before dosing.

         12. Drug or alcohol addiction requiring treatment in the 12 months before initial dosing.

         13. History of excessive alcohol consumption (on average more than 14 units of
             alcohol/week) during the past 12 months.

         14. Positive test results for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.

         15. Positive test results for drugs of abuse (benzodiazepines, cocaine, cannabinoids/THC,
             opiates and at screening only: amphetamines, barbiturates, methadone and
             phencyclidine).