None listed
Conditions
Brief summary
Perhexiline is the study drug that is being developed by Heart Metabolics, Ltd to potentially treat hypertrophic cardiomyopathy (HCM). HCM is a primary disease of the myocardium (the muscle of the heart) in which a portion of the myocardium is hypertrophied (thickened) without any obvious cause. The purpose of this study is to evaluate the effects of Perhexiline on heart conduction (the electrical activity of the heart) as compared to placebo (a tablet that will be made to look identical to the real drug but has no active ingredient) in healthy adult male and female volunteers. Moxifloxacin, also known as Avelox Registered Trademark', is a compound designed as an antibiotic that is indicated for the treatment of adults with infections. Moxifloxacin is known to have minor effects on heart conduction.
Interventions
This is a single study with 2 separate phases (as approved by an ethics committee). In the pilot phase of this study, a single cohort of 10 subjects will be dosed with open-label perhexiline oral tablets as follows: Day 1 and 2 - 200 mg every 12 hours, Day 3 and 4 - 200 mg once on each day, Day 5 - 150 to 300 mg (as guided by individual Perhexiline plasma levels) and Day 6 - 400 mg once.
The Thorough QT (TQT) Phase of the study is blinded, randomized, placebo-controlled, parallel-arm design with
This is a single study with 2 separate phases (as approved by an ethics committee). In the pilot phase of this study, a single cohort of 10 subjects will be dosed with open-label perhexiline oral tablets as follows: Day 1 and 2 - 200 mg every 12 hours, Day 3 and 4 - 200 mg once on each day, Day 5 - 150 to 300 mg (as guided by individual Perhexiline plasma levels) and Day 6 - 400 mg once. The Thorough QT (TQT) Phase of the study is blinded, randomized, placebo-controlled, parallel-arm design with a nested crossover comparison to moxifloxacin. Up to 100 subjects will participate in this phase, randomized in a 2:1:1 ratio into treatment assignments as listed below: Day -2 - Placebo Perhexiline (all 3 groups) Day -1 Placebo Moxifloxacin (Groups 1 and 2a), Moxifloxacin 400 mg (Group 2b) Days 1 to 6 - Perhexiline (Group 1), Placebo Perhexiline (Groups 2 a and 2b) Day 7 - Placebo Moxifloxacin (Groups 1 and 2b), Moxifloxacin (Group 2a) Dosing for Days 1 to 6 is as follows: Subjects Randomized to Perhexiline: Days 1 to 2 - 2 x 100 mg Perhexiline in the morning - 2 x 100 mg Perhexiline in the evening Days 3 to 4 - 2 x 100 mg Perhexiline in the morning - No evening dose Day 5 - Single dose of Perhexiline of between 150 and 300 mg, guided by subject's plasma Perhexiline level Day 6 - 4 x 100 mg Perhexiline in the morning - No evening dose Subjects Randomized to Placebo: Days 1 to 2 - 2 x 100 mg Placebo in the morning - 2 x 100 mg Placebo in the evening Days 3 to 4 - 2 x 100 mg Placebo in the morning - No evening dose Day 5 - 3 x 100 mg Placebo and 2 x 25 mg Placebo in the morning - No evening dose Day 6 - 4 x 100 mg Placebo in the morning - No evening dose On Day 7, all subjects will receive either Moxifloxacin 400 mg or Placebo, orally once. Subjects enrolled in both the Pilot Phase and the TQT Phase of the study will remain in the unit for the duration of the dosing period, and protocol compliance will be strictly adhered to.
Sponsors
Heart Metabolics, Ltd.
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy, non-smoking, male or female subjects ages 18 to 55 years inclusive, at the time of informed consent 2. Body mass index (BMI) of 18 to 30 kg/m2 inclusive, at Screening 3. Females must not be lactating or pregnant at Screening or Baseline 4. Provide written informed consent 5. Willing and able to comply with all aspects of the protocol
Exclusion criteria
1. CYP2D6 poor metabolizer, as determined via genotype 2. Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks before dosing 3. Evidence of disease that may influence the outcome of the study within 4 weeks before dosing 4. Any history of gastrointestinal surgery that may affect the pharmacokinetic profile of either study drug 5. Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, ECG finding, or laboratory test results that requires medical treatment at Screening or Baseline 6. History of any medical condition which, in the opinion of the investigator, may interfere with study procedures or compromise subject safety 7. A prolonged QT/corrected QT interval (QTc) interval (QTc > 450 ms), inverted or flat T waves that may interfere with QT analysis at Screening or Baseline, or any other clinically significant ECG abnormalities at Screening or Baseline 8. History of risk factors for torsade de pointes or the use of concomitant medications that prolong the QT/QTc interval 9. Persistent systolic blood pressure (BP) > 130 mmHg or < 90 mmHg and diastolic BP >85 mmHg or <50 mmHg at Screening or Baseline 10. Heart rate < 50 or > 100 beats/minute at Screening 11. History of prolonged QT/QTc interval 12. History of myocardial infarction or active ischemic heart disease 13. History of clinically significant arrhythmia or uncontrolled arrhythmia 14. Known history of clinically significant drug allergy (including to study drugs or any of their excipients) at Screening or Baseline 15. Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening or Baseline 16. Active viral hepatitis (B or C) as demonstrated by positive serology at Screening 17. History of drug or alcohol dependency or abuse within the 2 years before Screening, or who have a positive urine drug or alcohol test at Screening or Baseline 18. Use of recreational drugs 19. Intake of caffeinated beverages or food within 72 hours before dosing 20. Intake of nutritional supplements, juice, and herbal preparations or other foods or beverages that may affect the various drug metabolizing enzymes and transporters (eg., alcohol, grapefruit, grapefruit juice, apple or orange juice, vegetables from the mustard green family) within 1 week before dosing 21. Intake of herbal preparations containing St John's Wort within 4 weeks before dosing 22. Use of prescription drugs within 4 weeks before dosing 23. Intake of over-the-counter (OTC) medications within 2 weeks before dosing 24. Smoking or use of tobacco or nicotine-containing products within 4 weeks before dosing 25. Engagement in strenuous exercise within 2 weeks before dosing 26. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days preceding informed consent
Outcome results
None listed