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

A Pharmacokinetic Bridging Study of Film-Coated Tablets 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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: 100mg IkT-148009 Wet; Drug: 100mg IkT-148009 Dry; Drug: 200 mg Itraconazole; Drug: 50mg IkT-148009 Wet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Part A IkT-148009 Dry/Wet; 100mg IkT-148009 Wet & 100mg IkT-148009 Dry	Drug: 100mg IkT-148009 Wet; 100mg wet tablet formulation; Drug: 100mg IkT-148009 Dry; 100mg dry tablet formulation
Active Comparator: Part B - Ikt-148009 wet/ Itraconazole; 200 mg Itraconazole & 50mg IkT-148009 Wet	Drug: 200 mg Itraconazole; 2 100mg capsules; Drug: 50mg IkT-148009 Wet; 50mg wet tablet formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Safety	Changes in vital sign measurements including HR and blood pressure.	Through study completion, an average of 17 days
Patient Safety	Changes in clinical laboratory data consisting of CBC, Serum Chemistry, FSH	Through study completion, an average of 17 days
Patient Safety	Electrocardiogram [ECG] parameters of ventricular rate, RR or PR interval, QRS complex, and QTcF interval.	Through study completion, an average of 17 days
Patient Safety	C-SSRS assessment values.	Through study completion, an average of 17 days
Pharmacokinetic parameters in the absence or presence of itraconazole:	Pharmacokinetic parameters: • Area under the concentration-time curve from time zero to 96 hours (AUC0-∞)	Through study completion, an average of 17 days
Pharmacokinetic parameters in the absence or presence of itraconazole:	Pharmacokinetic parameters: • Maximum plasma concentration (Cmax)	Through study completion, an average of 17 days
Pharmacokinetic parameters in the absence or presence of itraconazole:	Pharmacokinetic parameters: • Area under the concentration-time curve from time zero to last time point (AUC0-last)	Through study completion, an average of 17 days
Assess the pharmacokinetics (PK) of IkT-148009	Pharmacokinetic parameters: • Area under the concentration-time curve from time zero to 96 hours (AUC0-∞)	Through study completion, an average of 17 days
Assess the pharmacokinetics (PK) of IkT-148009	Pharmacokinetic parameters: • Maximum plasma concentration (Cmax)	Through study completion, an average of 17 days
Assess the pharmacokinetics (PK) of IkT-148009	Pharmacokinetic parameters: • Area under the concentration-time curve from time zero to last time point (AUC0-last)	Through study completion, an average of 17 days
Patient Tolerability	Adverse event reporting	Through study completion, an average of 17 days

Collaborators and Investigators

• Sponsor: Inhibikase Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2023
• Primary Completion (Actual): August 17, 2024
• Study Completion (Actual): August 27, 2024

Study Registration Dates

• First Submitted: September 12, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 16, 2024

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: October 15, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: IkT-148009-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No