| Eligibility |
Inclusion Criteria:
1. Healthy, non-smoking (from at least 6 months prior to study drug administration), male
volunteers, 18-65 years of age, inclusive.
2. BMI that was within 18.5 and 30.0 kg/m², inclusive.
3. Healthy, according to the medical history, ECG, vital signs, laboratory results and
physical examination as determined by the PI/Sub-Investigator.
4. Systolic blood pressure between 95-140 mmHg, inclusive, and diastolic blood pressure
between 55-90 mmHg, inclusive, and heart rate between 50-100 bpm, inclusive, unless
deemed otherwise by the PI/Sub-Investigator.
5. Clinical laboratory values within BPSI's most recent acceptable laboratory test range,
and/or values were deemed by the PI/Sub-Investigator as "Not Clinically Significant".
6. Ability to comprehend and be informed of the nature of the study, as assessed by BPSI
staff. Capable of giving written informed consent prior to any study- related
procedure. Must have been to communicate effectively with clinic staff.
7. Ability to fast for at least 10 hours and consume a high-fat, high-calorie meal, as
well as standard meals.
8. Ability to fast for at least 14 hours and consume standard meals.
9. Availability to volunteer for the entire study duration and was to adhere to all
protocol requirements.
10. Agreed not to have a tattoo or body piercing until the end of the study.
11. Agreed not to receive the COVID-19 vaccination from 7 days prior to the first study
drug dose until 7 days after the last study drug administration in the study.
12. Agreed not to drive or operate heavy machinery if feeling dizzy or drowsy following
study drug administration until full mental alertness was regained.
13. Males who were to father children agreed to use medically acceptable methods of
contraception and to not donate sperm during the study and for 60 days after the last
study drug administration.
Medically acceptable methods of contraception included using a condom with a female partner
of child-bearing potential who was using oral contraceptives, hormonal patch, implant or
injection, intrauterine device, or diaphragm with spermicide. Abstinence as a method of
contraception is acceptable if it was in line with the preferred and usual lifestyle of the
study participant.
If a subject's partner became pregnant during his participation in the study and for 60
days after he has completed his last study drug administration, he must have informed BPSI
staff immediately.
Exclusion Criteria:
1. Known history or presence of any clinically significant hepatic, renal/genitourinary,
gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine,
immunological, musculoskeletal, neurological, psychiatric, dermatological or
hematological disease or condition unless determined as not clinically significant by
the PI/Sub-Investigator.
2. Clinically significant history or presence of any clinically significant
gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel disease),
unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting), or other conditions
known to interfere with the absorption, distribution, metabolism or excretion of the
drug experienced within 7 days prior to first study drug administration, as determined
by the PI/Sub-Investigator.
3. Estimated creatinine clearance <70 ml/min.
4. Presence of any clinically significant illness within 30 days prior to first dosing,
as determined by the PI/Sub-Investigator.
5. Presence of any significant physical or organ abnormality as determined by the
PI/Sub-Investigator.
6. A positive test result for any of the following: HIV, Hepatitis B surface antigen,
Hepatitis C, drugs of abuse (marijuana, amphetamines, barbiturates, cocaine, opiates,
phencyclidine and benzodiazepines), breath alcohol test and cotinine.
7. Known history or presence of:
- Alcohol abuse or dependence within one year prior to first study drug
administration;
- Drug abuse or dependence;
- Hypersensitivity or idiosyncratic reaction to Orfiril Long, its excipients,
and/or related substances;
- Suicidal ideation or suicidal behavior, as assessed by the Columbia Suicide
Severity Rating Scale (baseline version) - Appendix C (Refer to Appendix 16.1.1)
- Lactose intolerance, galactose intolerance, Lapp lactase deficiency or
glucose-galactose malabsorption;
- Food allergies;
- Presence of any dietary restrictions unless deemed by the PI/Sub-I as "Not
Clinically Significant".
- Family history of hereditary neurometabolic syndromes due to mitochondrial enzyme
polymerase;
- Known urea cycle disorder;
- Known porphyria;
- Coagulation disorder;
- Family history of liver disease;
- Severe allergic reactions (e.g., anaphylactic reactions, angioedema).
8. Intolerance to and/or difficulty with blood sampling through venipuncture.
9. Abnormal diet patterns (for any reason) during the four weeks preceding the study,
including fasting, high protein diets etc.
10. Individuals who have donated, in the days prior to first study drug administration:
- 50-499 mL of blood in the previous 30 days;
- 500 mL or more in the previous 56 days.
11. Donated plasma by plasmapheresis within 7 days prior to first study drug
administration.
12. Individuals who have participated in another clinical trial or who received an
investigational drug within 30 days prior to first study drug administration.
13. Use of any enzyme-modifying drugs and/or other products, including strong inhibitors
of cytochrome P450 (CYP) enzymes (e.g., cimetidine, fluoxetine, quinidine,
erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals)
and strong inducers of CYP enzymes (e.g., barbiturates, carbamazepine,
glucocorticoids, phenytoin, St. John´s Wort, and rifampicin) in the previous 30 days
before first study drug administration.
14. Used of any monoamine oxidase (MAO) inhibitors (e.g., phenelzine, tranylcypromine)
within 30 days prior to first study drug administration.
15. Used of any prescription medication within 14 days prior to first study drug
administration.
16. Used of any over-the-counter medications (including oral multivitamins, herbal and/or
dietary supplements) within 14 days prior to first study drug administration.
17. Consumed food or beverages containing grapefruit and/or pomelo within 10 days prior to
first study drug administration.
18. Consumed food or beverages containing caffeine/methylxanthines, poppy seeds and/or
alcohol within 48 hours before dosing in each study period.
19. Individuals who had undergone any major surgery within 6 months prior to the start of
the study, unless deemed otherwise by PI/Sub-Investigator.
20. Difficulty with swallowing whole tablets.
21. Unable or unwilling to provide informed consent.
22. Had a tattoo or body piercing within 30 days prior to first study drug administration.
23. A subject who, in the opinion of the investigator or designee, is considered
unsuitable or unlikely to comply with the study protocol for any reason.
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