A PK Study of IkT-148009 in Older and Elderly Healthy Subjects

This is a two-part study. Part A consists of two different IkT-148009-201 solid dosage formulations that are being evaluated to determine their steady-state pharmacokinetic profile.

Part B is a drug-drug interaction (DDI) study focused on evaluating the impact of a strong CYP3A inhibitor on the preferred dosage determined in part A.

This is a two-part study.

Part A is a single dose (7-day) study to determine the safety, tolerability and pharmacokinetics (PK) of two different tablet formulations of IkT-148009 in older and elderly healthy subjects.

Subjects in each cohort of the study will be admitted to the unit the day prior to the expected day of dosing and will be confined to the unit for approximately 12 days. Each cohort will consist of six (6) subjects who will receive treatment with one of two formulations of IkT- 148009 film-coated tablets at a single dose once daily for 7 days.

Part B is a Drug-Drug Interaction (DDI) study to determine the effect of itraconazole on the pharmacokinetics of IkT-148009.

Subjects in each cohort of the study will be admitted to the unit the day prior to the expected day of dosing in each period and will be confined to the unit for approximately 6 days in period 1 and 10 days in period 2. Up to eight (8) subjects will be evaluated in a two-period design in the fed state.

In Period 1, the 50 mg film-coated IkT-148009 tablet dose pharmacokinetics will be measured, followed by a 7-day washout. In Period 2, the same eight subjects will first be administered a 200 mg once daily capsule dose of itraconazole for four days. On Period 2 day 4 subjects will take a single 200 mg capsule dose of itraconazole, followed one hour later by a 50 mg film-coated tablet dose of IkT-148009.

Eligibility Criteria:
Inclusion Criteria:

1. Subject must have all questions about the study answered and must have signed the informed consent document before any study-specific procedures are performed.
2. Healthy ambulatory male and female subjects with no history or evidence of clinically relevant medical disorders as determined by the Investigator in consultation with the Sponsor.
3. Bodyweight \> 50 kg and body mass index (BMI) \> 18.0 and \< 32.0 kg/m2.
4. Physical examination, clinical laboratory values, vital signs, and electrocardiogram (ECG) data.
5. Female subjects must be postmenopausal, permanently sterile (bilateral tubal occlusion), or of childbearing potential with a negative pregnancy test, non-breastfeeding, and using two highly effective methods of birth control.
6. Male subjects must agree to practice an acceptable method of highly effective birth control.
7. Males must be willing to abstain from sperm donation from the screening visit, while on study and through 30 days after receiving the last dose of study drug.

Exclusion Criteria:

1. Any subject with previous exposure to imatinib or known hypersensitivity to imatinib.
2. Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at the screening and admission visits.
3. Clinically significant abnormal physical examination or 12-lead electrocardiogram (ECG) at the screening or admission visits.
4. Clinically significant abnormal renal function.
5. Significant history (within six months prior to receiving the study drug) and/or presence of hepatic, renal, cardiovascular, pulmonary, gastrointestinal, endocrinological, hematological, dermatological, psychiatric, neurological, immunologic, ophthalmologic, metabolic, fluid retention and edema, bleeding disorders including hemorrhage or oncological disease.
6. Any subject with a history, presence and/or current evidence of serologic positive result for hepatitis B surface antigen, hepatitis C antibodies, or HIV antibodies 1 or 2.
7. Recent history (within previous six months prior to screening) of alcohol or drug abuse (as judged by the investigator), or has consumed \> 2 alcohol drinks/day during the last three months prior to screening.
8. Any subject who currently uses or has regularly used tobacco or tobacco-containing products (cigarettes, pipes, etc.) for at least 30 days prior to screening or positive urine cotinine screen at the screening or admission visits.
9. Any subject who has received treatment with an investigational drug during the 30 days prior to screening. Exposure to an investigational medical device within 30 days of screening.
10. Use of agents known to affect drug metabolism: use of any known CYP3A4 inducers and/or inhibitors or consumed grapefruit juice, grapefruit, Seville oranges or St John's Wort or products containing these within 14 days prior to first administration of study drug. Strong inducers of CYP3A4 include dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin and phenobarbital. Strong inhibitors of CYP3A4 include ketoconazole, itroconazole, clarythromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole.
11. Investigative site personnel or their immediate families (spouse, parent, child or sibling whether biological or legally adopted).
12. Any subject unwilling or unable to comply with study procedures.
13. Pregnant or nursing women.
14. Anyone who does not meet the requirements for exclusion of certain concomitant medications as defined in Section 7.5.