Effect of a Single Oral Dose of Moxidectin on the Cardiac QT Interval of Healthy Volunteers
Condition: QT Effects in Healthy Volunteers
Intervention: Moxidectin; Placebo
Intervention description: Moxidectin is a broad spectrum macrocyclic lactone endectocide
Intervention MeSH terms: Moxidectin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 60.0
Sex: Male
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study will investigate the effect of a single oral dose of moxidectin on the QT interval
      associated with moxidectin plasma concentrations.

      The effect of moxidectin on other ECG intervals, and on safety, will also be assessed, as
      will preliminary pharmacokinetics and metabolism
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy male between 18 and 50 years of age (inclusive);

          2. Body mass index (BMI) of 18 to 30 kg/m2 (inclusive) and a minimum weight of 50 kg (110
             lbs);

          3. Biologically or surgically sterile or must commit to using a reliable method of birth
             control, in the opinion of the investigator, from Screening through the duration of
             the study;

          4. Willing and able to give written informed consent.

        Exclusion Criteria:

          1. Unwilling to abstain from alcohol, caffeine, xanthine containing products, Seville
             oranges, grapefruit juices, and fish liver oils within 72 hours before Check in (Day
             -1) and throughout the inpatient period of the study;

          2. Less than 1 bowel movement every 24 hours in the absence of any laxative, suppository,
             or enema use during the month before Screening;

          3. Abnormal fecal consistency within 24 hours of Check in (Day -1);

          4. Clinically relevant abnormal findings on medical history, clinical laboratory test
             results, vital sign measurements, safety 12 lead ECG results, or physical examination
             at Screening or Baseline which, in the opinion of the investigator, would interfere
             with dosing, jeopardize the safety of the subject, or impact the validity of the study
             results;

          5. History of clinically significant dermatologic, gastrointestinal, renal, hepatic,
             neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or
             cardiovascular disease or any other condition which, in the opinion of the
             investigator, would interfere with dosing, jeopardizes the safety of the subject, or
             impacts the validity of the study results;

          6. History or hypersensitivity or allergic reactions to ivermectin, moxidectin, or any of
             the ingredients in the study drug as described in the Investigator's Brochure;

          7. Any condition that may affect oral drug absorption (eg, previous surgery on the
             gastrointestinal tract including removal of parts of the stomach, bowel, liver, gall
             bladder, or pancreas);

          8. History of risk factors for torsades de pointes, including unexplained syncope, known
             long QT syndrome, heart failure, myocardial infarction, angina, or clinically
             significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or
             hypomagnesemia. Subjects are also excluded if there is a family history of long QT
             syndrome or Brugada syndrome;

          9. A sustained supine systolic blood pressure >150 mm Hg or <90 mm Hg or a supine
             diastolic blood pressure >95 mm Hg or <50 mm Hg at Screening or Check in (Day -1).
             Blood pressure may be retested twice in the supine position. The blood pressure
             abnormality is considered sustained if either the systolic or the diastolic blood
             pressure values are outside of the stated limits after 3 assessments, and the subject
             will not to be randomized;

         10. A resting heart rate (HR) of <40 beats per minute (bpm) or >100 bpm when vital signs
             are measured at Screening or Check in (Day -1);

         11. An uninterpretable or abnormal screening ECG indicating a second or third degree
             atrioventricular block, or 1 or more of the following: QRS interval >110 milliseconds
             (msec); QT interval corrected by Fridericia's formula (QTcF) >450 msec; PR interval
             >200 msec; or any rhythm other than sinus rhythm that is interpreted by the
             investigator to be clinically significant;

         12. Concomitant use of prescription medications, including medications known to prolong
             the corrected QT interval (QTc) or herbal preparations, within 14 days or 5 half-lives
             (whichever is longer) before study drug dosing, or use of an over the counter (OTC)
             medication or vitamins within 7 days before study drug dosing;

         13. Received an investigational drug during the 30 days, or 5 half lives of the study drug
             (whichever is longer), before Check in (Day -1) or is planning to receive another
             investigational drug at any time during the study;

         14. History or presence of alcohol abuse (defined as consumption of more than 210 mL of
             alcohol per week, or the equivalent of fourteen 4 ounce [oz] glasses of wine or
             fourteen 12 oz cans/bottles of beer or wine coolers per week) within 6 months before
             Screening or positive alcohol test at Screening or Check-in (Day -1);

         15. History or presence of substance abuse within the past 2 years or positive drug screen
             test at Screening or Check in (Day -1);

         16. Current use or has used tobacco- or nicotine-containing products (eg, cigarettes,
             cigars, chewing tobacco, snuff, etc.) within 14 days before study drug dosing;

         17. Blood donation or significant blood loss within 30 days before Check-in (Day -1) or
             donated plasma within 7 days before Check-in (Day -1);

         18. Presence of hepatitis B surface antigen or antibodies to human immunodeficiency virus
             (HIV) or hepatitis C virus at Screening;

         19. Poor venous access in both arms;

         20. Unable to understand verbal or written English or any other language for which a
             certified translation of the informed consent form is available;

         21. For any reason, is deemed by the investigator or medically qualified designee to be
             inappropriate for this study, including a subject who is unable to communicate or
             cooperate with the investigator, and/or is unwilling to comply with protocol defined
             procedures and complete the study.