A Study to Assess Single and Multiple Doses of IkT-148009 in Healthy Elderly Participants and Parkinson's Patients

Phase 1

Completed

• Conditions: Parkinson Disease; Healthy Elderly
• Interventions: Drug: IkT-148009; Drug: Placebo

• Registration Number: NCT04350177
• Lead Sponsor: ABLi Therapeutics, Inc.

Brief Summary

This study investigates the safety and tolerability of drug IkT-148009 in healthy elderly volunteers (55 to 70 years old). This first-in-human study is designed in 3 parts. In Part A, healthy participants will take a single, oral dose of IkT-148009 or placebo. Part A participants will be at the study site for approximately 4 days. In Part B, healthy participants will take an oral dose of IkT-148009 once a day for 7 days. Part B participants will be at the study site for approximately 12 days. In Part C, Parkinson\'s patients will take an oral dose of IkT-148009 once a day for 7 days. Part C participants will be at the study site for approximately 12 days.

Detailed Description

This is a randomized, Phase 1 study in older adult or elderly healthy volunteer subjects with subsequent extension into Parkinson patients to identify the safety, tolerability, maximum tolerated dose (MTD) and the pharmacokinetic (PK) profile of IkT-148009 capsules given as single or multiple doses.

In Part A (SAD) cohorts will consist of eight (8) subjects, six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo. Sentinel dosing will be employed on the first day of each cohort, with one subject randomized to receive IkT-148009 and the other placebo. These two subjects in each cohort will be monitored for 48 hours after dosing before deciding to dose the remainder of the cohort. The other six subjects in the first cohort will be dosed approximately 48 hours later. Each cohort will be monitored for at least 48 hours before deciding whether to administer drug to the sentinel pair for the next cohort. Each cohort will be dosed at approximately weekly intervals to allow adequate time for collection and review of safety and PK data.

A Safety Review Committee (SRC) will evaluate all available safety, tolerability, and PK data for each cohort. Escalation to a next dose will be undertaken only after these data have been reviewed by the SRC and agreement reached that it is safe to increase the dose. The SRC will not receive any unblinded PK data unless they agree to unblind a subject and/or cohort based on the completed safety review.

In Part B (MAD) cohorts will consist of eight (8) subjects, six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo daily for up to seven consecutive days. Subjects in each cohort will be observed for 48 hours after their last dose before deciding to initiate the next (higher dose) cohort. Each cohort will be dosed at approximately weekly intervals in order to allow adequate time for collection and review of safety and PK data. At the discretion of the SRC, MAD cohorts may be added consisting of eligible participants with Parkinson's Disease (Part C).

In Part C (MAD with Parkinson\'s Disease) eligible PD participants will arrive the evening before initiation of study drug dosing. No Parkinsonism medications will be given after midnight, the following morning potential participants will be clinically assessed in the practically-defined OFF state using MDS-UPDRS Part III. Cohorts will consist of eight (8) subjects, six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo daily for up to seven consecutive days. Subjects in each cohort will be observed for 48 hours after their last dose before deciding to initiate the next (higher dose) cohort. Each cohort will be dosed at approximately weekly intervals in order to allow adequate time for collection and review of safety and PK data.

Study Timeline

• Study First Submitted: 2019-12-26
• Study First Submitted QC: 2020-04-15
• Study First Posted: 2020-04-16
• Study Start: 2021-02-16
• Primary Completion: 2022-10-30
• Study Completion: 2023-01-30
• Status Verified: 2023-02
• Last Update Submitted: 2025-03-06
• Last Update Posted: 2025-03-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 101

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Single Ascending Dose (SAD)	Placebo	In Part A, cohorts will consist of eight (8) subjects; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.
Single Ascending Dose (SAD)	IkT-148009	In Part A, cohorts will consist of eight (8) subjects; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.
Multiple Ascending Dose (MAD)	IkT-148009	In Part B, cohorts will consist of eight (8) subjects; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.
Multiple Ascending Dose (MAD)	Placebo	In Part B, cohorts will consist of eight (8) subjects; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.
Multiple Ascending Dose (MAD) Parkinson's patients	IkT-148009	In Part C, cohorts will consist of eight (8) patients; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.
Multiple Ascending Dose (MAD) Parkinson's patients	Placebo	In Part C, cohorts will consist of eight (8) patients; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.

Primary Outcome Measures

Name	Time	Method
Safety: incidence of abnormal vital sign measurements	Safety assessments performed from Day 1 through Day 14	body temperature by mouth, blood pressure, pulse rate, pulse oximetry, respiration rate
Safety: incidence of abnormal electrocardiogram [ECG]	Safety assessments performed from Day 1 through Day 14	An ECG traces the electrical activity of the heart.
Tolerability (adverse event reporting)	Day 1 through 14 days post last dose	Adverse events reported
Pharmacokinetic AUC of IkT-148009	Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.	Area under the concentration-time curve (AUC0-∞)
Pharmacokinetic Cmax of IkT-148009	Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.	Maximum plasma concentration (Cmax)
Pharmacokinetic Tmax of IkT-148009	Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.	Time to reach maximum concentration (Tmax)
Safety: incidence of abnormal Clinical Laboratory Data	Safety assessments performed from Day 1 through Day 14	Clinical chemistry tests will include albumin, alkaline phosphatase, total bilirubin, calcium, cholesterol, creatinine, creatinine clearance, creatinine kinase (CK), gamma-glutamyltransferase (γ-GT), glucose, lactate dehydrogenase (LDH), inorganic phosphorus, lipase, amylase, potassium, magnesium, total protein, aspartate transaminase (AST), alanine transaminase (ALT), sodium, triglycerides, urea and uric acid, bicarbonate and chloride. TSH levels will also be monitored. CBC assessments will include hemoglobin, hematocrit, red blood cell (RBC) count, reticulocyte count, white blood cells (WBC) count with differential, platelet count and PT-INR. PT-INR should be reported in both prothrombin time and international normalized ratio. Men and women will undergo additional laboratory tests for reproductive organ function to include leutenizing hormone (LH), follicle stimulating hormone (FSH), testosterone and inhibin B.
Safety: C-SSRS	Safety assessments performed from Day 1 through Day 14	Columbia Suicide Severity Rating Scale questionaire
Pharmacokinetic AUC to last time point of IkT-148009	Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.	Area under the concentration-time curve from time zero to last time point (AUC0-last)
Pharmacokinetic distribution half-life of IkT-148009	Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.	The distributional half-life and terminal half-life (t1/2)
Pharmacokinetic exposure of IkT-148009 steady-state	Part B, C: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192 hours post-dose.	Exposure (AUC SS)
Pharmacokinetic trough concentration of IkT-148009	Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.	Exposure (Ctrough)
Pharmacokinetic concentration of IkT-148009 steady-state at maximum concentration	Part B, C: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192 hours post-dose.	Exposure (Cmax SS)

Trial Locations

Locations (4)

Quest Research Institute LLC; 🇺🇸 Farmington Hills, Michigan, United States

Collaborative Neuroscience Research, LLC; 🇺🇸 Long Beach, California, United States

Hassman Research Institute; 🇺🇸 Marlton, New Jersey, United States

Velocity Clinical Research; 🇺🇸 Hallandale Beach, Florida, United States