None listed
Conditions
Brief summary
This is a single centre, randomized, double-blind, placebo-controlled, sequential, single dose-escalation study of AK-119 administered to healthy adults and multiple dose-escalation study of AK-119 administered to healthy adults. The study comprises three parts A,B & C. Part A of the study is a single dose escalation arm. The safety data will be reviewed after each Cohort prior to dose escalation. The selected dose cohort will participate in a two-way crossover design and return to the clinical unit to receive AK-119/placebo administration of the same for evaluation of the food effect after a washout of at least 7 days. In Part B All subjects will be admitted to the Phase 1 unit on Day -1 for pre-treatment assessments then given a single dose of AK-119 or placebo once or twice daily from Day 1 to Day 7. They will remain inpatients until Day 10, returning as outpatients for follow-up assessments on Day 14. Part C will start after completing the multiple dose, dose escalation components in healthy volunteers in Part B, one cohort with healthy volunteers will be enrolled to receive 1 dose level of AK-119/placebo, as determined from the Part B in healthy volunteers. The dosing period will be upto 28 days as once or twice daily, commencing on Day 1 (dosing regimen to be determined from Part B).
Interventions
Part A, Single Ascending Dose (SAD), involves the oral capsule administration of 0.5 mg up to 24 mg (proposed dose levels are 0.5mg, 2mg, 6mg, 12mg, 24mg) of AK-119, each participant consuming one dose only. The one selected dose cohort will return for a food effect evaluation after at least a 7-day wash-out. The selected dose cohort will participate in a two-way crossover design and return to the clinical unit to receive AK-119/placebo administration of the same for evaluation of the food effe
Part A, Single Ascending Dose (SAD), involves the oral capsule administration of 0.5 mg up to 24 mg (proposed dose levels are 0.5mg, 2mg, 6mg, 12mg, 24mg) of AK-119, each participant consuming one dose only. The one selected dose cohort will return for a food effect evaluation after at least a 7-day wash-out. The selected dose cohort will participate in a two-way crossover design and return to the clinical unit to receive AK-119/placebo administration of the same for evaluation of the food effect after a washout of at least 7 days. Subjects will undergo the same study assessments in Period 2 as in Period 1, byby the Safety Review Committee (SRC), and will have their follow-up assessment visit 7 days after dose administration in their second period. Subjects will be randomised to receive either no breakfast or a high fat breakfast on the first period and the alternate breakfast in the second period. The cohort and dose selected for the food effect evaluation may be changed after review of the safety data from the first two cohorts of Part A. This part of the study can be conducted in parallel to the higher determined dosing for the subsequent groups. Part B, Multiple Ascending Dose (MAD): up to 16 (2 cohorts) of healthy volunteers will be dosed daily for seven days. Part C, Multiple Ascending Dose (MAD): One cohort of up to 8 healthy volunteers will be dosed daily for up to 28 days. The dose levels for Parts B and C will be selected following review of safety and pharmacodynamics data from the preceding part(s) of the study. Drug will be administrated at the site under supervision of trained staff monitoring adherence.
Sponsors
Akaal Pharma Pty 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
Healthy volunteer subjects eligible for inclusion in this study have to fulfil all of the following inclusion criteria: 1. Male and female subjects 18-55 years of age, inclusive, at the time of screening 2. Able to provide written informed consent prior to the performance of any study specific procedures 3. Subjects with a BMI between 18.0 and 30.0 kg/m2, inclusive 4. A 12-lead ECG at screening or pre-dose assessment that, in the opinion of the investigator, has no abnormalities that compromise subject’s safety in this study. 5. Female subjects of non-childbearing potential, defined as (1) having a documented tubal ligation at least 6 weeks prior to dosing; (2) having had a surgical bilateral oophorectomy (with or without hysterectomy); (3) at least 12 months of spontaneous amenorrhoea with follicle stimulating hormone (FSH) > 40 MIU/ml. 6. Female subjects of child-bearing potential with negative serum pregnancy test at screening and negative urine pregnancy test at check-in (Day -1), AND; • Agrees to abstinence for the duration of the study and until 4 weeks after dosing with study drug; • OR agrees to use condoms plus a highly-effective form of contraception (associated with a less than 1% failure rate when applied consistently and correctly); i.e. intra-uterine device or hormonal contraception associated with suppression of ovulation, from screening until 4 weeks after dosing with study drug; • OR has only same-sex partners when this is her preferred and usual lifestyle. 7. Male subjects with female partners of child-bearing potential must agree abstinence or to use condoms plus partner use of a highly-effective form of contraception (intrauterine device, hormonal contraception) for the duration of the study and until 12 weeks after dosing with study drug. They must also agree to not donate semen during the same time frame. 8. Negative Human Immunodeficiency Virus (HIV), Hepatitis B and Hepatitis C Screening test results 9. Subjects who are willing and able to comply with all study assessments and adhere to the protocol schedule. 10. The participant will be normotensive at screening with systolic blood pressure (BP) between 95 and 140mmHg, diastolic BP between 50 and 95mmHg, and heart rate (HR) between 55 and 90 beats per minutes (bpm).
Exclusion criteria
Healthy volunteer subjects fulfilling any of the following criteria are not eligible for inclusion in this study: 11. Have received any investigational research agent within 30 days or 5 half-lives (whichever is longer) prior to the first dose of Investigational Product. 12. Have received an investigational vaccine within 6 months, a live attenuated vaccine within 60 days or a registered vaccine within 30 days prior to the first dose of the Investigational Product. 13. Clinically significant history or presence of any gastrointestinal pathology (e.g., chronic diarrhoea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g., diarrhoea, vomiting), liver or kidney disease, Gilbert’s syndrome, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. 14. Any clinically significant history or presence of neurological, endocrinal, cardiovascular, pulmonary, haematological, malignant, immunologic, psychiatric, metabolic or other uncontrolled systemic disease 15. Have a bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws. 16. Have a psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder; disorder requiring lithium; or within five years prior to enrolment, a history of suicide plan 17. Any clinically significant abnormality at Screening determined by medical history, physical examination, blood chemistry, haematology, urinalysis and a 12-lead ECG, positive urine screen for drugs of abuse. 18. Any other condition which in the view of the Investigator is likely to interfere with the study or put the subject at risk. 19. Have clinical signs of active infection and/or a temperature of equal or greater than 38.0°C at the time of screening. Study entry may be deferred at the discretion of the Principal Investigator 20. Have evidence of drug abuse or positive urine drug screen at screening 21. Subjects who have smoked more than 10 cigarettes a day in the last 12 months 22. Have evidence of alcohol abuse within 6 months prior to screening visit (i.e., more than fourteen units of alcohol per week [1 Unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]) 23. Be unable to provide a pre-dose blood sample without undue trauma or distress 24. Anticipate surgery within the trial period or history of major surgery within 3 months of screening 25. History of hypersensitivity to any other S1P receptor modulator 26. Use of prescription medication (including anticoagulants) within 14 days prior to administration of study treatment or over-the-counter products (including natural food supplements, vitamins, garlic as a supplement) within 7 days prior to administration of study treatment, except for topical products without systemic absorption unless otherwise agreed by sponsor. 27. A depot injection or an implant of any drug within 3 months prior to administration of study treatment, with the exception of a contraceptive implant 28. Subjects with a history or presence (at screening or first baseline) of any clinically significant ECG abnormalities including, but not limited to any type of AV blocks or any of the following ECG abnormalities at screening or baseline: o PR > 220 ms o QRS complex > 120 msec o QTcF >470 msec (females) or > 450 msec (males) o Prominent U waves or any significant morphological changes other than non-specific T-wave changes 29. Subjects with a history or presence (at screening or first baseline) of any of the following cardiovascular findings: o Clinically significant ventricular or supraventricular arrhythmia (as judged by the investigator) o History or presence of coronary heart disease (stable or unstable), myocardial infarction, myocarditis, cardiomyopathy or heart failure o History or presence of long QT syndrome or any other cause of prolonged QT interval o History or cardiac catheter ablation o History or presence of symptomatic postural hypotension or syncopes 30. Subjects with a family history of congenital long QT syndrome or unexplained sudden cardiac death 31. Medications known to prolong the QTc interval 32. Subjects with symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction < 20%, transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months prior to study entry. 34. Subjects who are unable to return for all scheduled study visits 35. Any other condition, that in the opinion of the investigator would render the subject unsuitable for enrolment, or could interfere with the subject participating in and completing the study
Outcome results
None listed