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

NCT04350177 | Completed Phase 1 FDA Drug

• 1 other identifier: IkT-148009-101
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 4

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.

Conditions

Healthy Elderly; Parkinson Disease

Outcome Measures

Primary Outcomes (13)

• Safety: incidence of abnormal vital sign measurements

  body temperature by mouth, blood pressure, pulse rate, pulse oximetry, respiration rate

  Safety assessments performed from Day 1 through Day 14

• Safety: incidence of abnormal Clinical Laboratory Data

  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 assessments performed from Day 1 through Day 14

• Safety: incidence of abnormal electrocardiogram [ECG]

  An ECG traces the electrical activity of the heart.

  Safety assessments performed from Day 1 through Day 14

• Safety: C-SSRS

  Columbia Suicide Severity Rating Scale questionaire

  Safety assessments performed from Day 1 through Day 14

• Tolerability (adverse event reporting)

  Adverse events reported

  Day 1 through 14 days post last dose

• Pharmacokinetic AUC of IkT-148009

  Area under the concentration-time curve (AUC0-∞)

  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.

• Pharmacokinetic Cmax of IkT-148009

  Maximum plasma concentration (Cmax)

  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.

• Pharmacokinetic AUC to last time point of IkT-148009

  Area under the concentration-time curve from time zero to last time point (AUC0-last)

  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.

• Pharmacokinetic Tmax of IkT-148009

  Time to reach maximum concentration (Tmax)

  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.

• Pharmacokinetic distribution half-life of IkT-148009

  The distributional half-life and terminal half-life (t1/2)

  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.

• Pharmacokinetic trough concentration of IkT-148009

  Exposure (Ctrough)

  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.

• Pharmacokinetic concentration of IkT-148009 steady-state at maximum concentration

  Exposure (Cmax SS)

  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.

• Pharmacokinetic exposure of IkT-148009 steady-state

  Exposure (AUC SS)

  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.

Other Outcomes (10)

• Exploratory Biomarker Screen of protein factors

  Part B and C only, up to 1 year

• Exploratory Biomarker Screen of drug concentration

  Part B and C only, up to 1 year

• Change from Baseline to Final visit in the MDS-UPDRS Motor Subscale (Part III) Score

  Part C only, up to 1 year

Study Arms (3)

Single Ascending Dose (SAD)

ACTIVE COMPARATOR

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.

Drug: IkT-148009; Drug: Placebo

Multiple Ascending Dose (MAD)

ACTIVE COMPARATOR

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.

Drug: IkT-148009; Drug: Placebo

Multiple Ascending Dose (MAD) Parkinson's patients

ACTIVE COMPARATOR

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.

Drug: IkT-148009; Drug: Placebo

Interventions

IkT-148009 DRUG

Oral administration gelatin capsule

Multiple Ascending Dose (MAD); Multiple Ascending Dose (MAD) Parkinson's patients; Single Ascending Dose (SAD)

Placebo DRUG

Oral administration gelatin capsule

Multiple Ascending Dose (MAD); Multiple Ascending Dose (MAD) Parkinson's patients; Single Ascending Dose (SAD)

Eligibility Criteria

• Age: 55 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Subject must have all questions about the study answered and must have signed the informed consent document before any study-specific procedures are performed.
• \. Men or women aged 55 to 70 years (both inclusive) of any race. 3. Subjects must be otherwise healthy and ambulatory, with no history or evidence of clinically relevant medical disorders as determined by the Investigator in consultation with the Sponsor.
• \. Mini Mental State Examination (MMSE) ≥ 28 at Screening (V1) and Baseline (V2).
• \. Physical examination, clinical laboratory values, vital signs (as defined in the CRU standard operating procedure \[SOP\]), and the electrocardiogram (ECGs) are clinically acceptable to the Investigator. Body weight ≥ 45 kg at screening and baseline visits. Body Mass Index (BMI) ≥ 18 and ≤30 kg/m2 at screening.
• \. Female subjects must be postmenopausal (12 months without menses and confirmed by follicle stimulating hormone \[FSH\] \> 40 mIU/mL) or surgically sterile (hysterectomy or bilateral oophorectomy) or sterile for other medical reason (i.e., able to document premature low ovarian reserve, birth defect, other). Women who are several years postmenopausal may be considered for enrollment even with \[FSH\] below this threshold.
• \. Male subjects must agree to practice an acceptable method of highly effective birth control from the Screening visit, while on study and for 7 days after receiving the last dose of study drug. Highly effective methods of birth control include sexual abstinence; vasectomy; or a condom with spermicide (men) in combination with their partner's highly effective method.
• \. 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.
• Part C:
• Participants must be eligible as in Part A and B, with the following differences/additions:
• \. MMSE ≥ 26 at screening (V1) and Baseline (V2) 10. Diagnosis of Parkinson's Disease (consistent with the UK PD Society Brain Bank Criteria for the Diagnosis of PD), with bradykinesia and a clear motor response to levodopa.
• \. Hoehn \& Yahr staging of 3 or less in the ON state. 12. Good clinical response to levodopa as judged by participant and investigator.
• \. Stable doses of all PD medications for at least 4 weeks prior to Screening. 14. Approved by an Enrollment Authorization Committee (EAC).

You may not qualify if:

• \. Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at the screening and admission visits. Abnormalities considered to be non-clinically significant by the Investigator are acceptable.
• \. Significant history (within six months prior to receiving the study drug) and/or presence of clinically significant medical, surgical or psychiatric disorder. Subjects with co-morbid conditions that are stable and controlled may remain eligible (stable defined as no change in the dose or frequency of medications over the prior three months).
• \. For optional lumbar puncture: participants with bleeding disorders, relevant lab abnormalities (Screening INR greater than 1.4, platelets less than 50), relevant blood dyscrasias, prior intolerance of LP, anatomical reasons preventing safe or successful collection of fluid (skin infection at site of puncture, relevant spine surgery, spinal deformity, etc), known intracranial space-occupying lesions with mass effect, posterior fossa masses, or relevant brain malformations (Arnold-Chiari malformation, etc), exam findings suggestive of increased intracranial pressure, or known allergy/sensitivity to lidocaine or its derivatives will not be eligible.
• \. eGFR \< 60 mL/min 6. Creatinine, Amylase and/or Lipase \> ULN 7. Any malignancy in the 5 years prior to screening excluding basal cell carcinoma or squamous cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated.
• \. 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. Subjects considered to be cured for hepatitis C will be eligible. 9. 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 (one glass is approximately equivalent to: beer \[284 mL\], wine \[125 mL/4 ounces\], or distilled spirits \[25 mL/1 ounce\]). Subjects that consume three glasses of alcoholic beverages per day but less than 14 glasses per week may be enrolled at the discretion of the Investigator. Positive screens for alcohol or controlled substances at the screening or admission visits will disqualify a subject from study participation.
• \. Any subject with known hypersensitivity to IkT-148009.
• \. Donation of blood or acute loss of blood within 60 days prior to screening visit.
• \. Any subject who has received treatment with an investigational drug during the 30 days prior to screening.
• \. Investigative site personnel or their immediate families (spouse, parent, child or sibling whether biological or legally adopted).
• \. Any subject unwilling or unable to comply with study procedures.
• and in addition for Part C:
• \. For optional lumbar puncture: participants with bleeding disorders, relevant lab abnormalities (Screening INR greater than 1.4, platelets less than 50), prior intolerance of LP, anatomical reasons preventing safe or successful collection of fluid (skin infection at site of puncture, relevant spine surgery, spinal deformity, etc), known intracranial space-occupying lesions with mass effect, posterior fossa masses, or relevant brain malformations (Arnold-Chiari malformation, etc), exam findings suggestive of increased intracranial pressure, or known allergy/sensitivity to lidocaine or its derivatives will not be eligible.
• \. Diagnosis of secondary or atypical parkinsonism 17. Prior neurosurgery for PD or treatment with DUODOPA or infused apomorphine 18. Concurrent use of neuroleptic medications or other dopamine antagonists. 19. Severe or disabling fluctuations or dyskinesias that would, in the opinion of the investigator, interfere with completion of the study 20. Clinically significant hallucinations or delusions that, in the opinion of the investigator or EAC, may preclude completion of the study 21. Clinically significant orthostatic hypotension that, in the opinion of the investigator, may preclude completion of the study 22. Currently active major depression as determined by BDI-II score of \>19 23. Previous surgical procedure for PD.

Sponsors & Collaborators

• ABLi Therapeutics, Inc.: lead

Study Sites (4)

Collaborative Neuroscience Research, LLC

Long Beach, California, 90806, United States

Location

Velocity Clinical Research

Hallandale, Florida, 33009, United States

Location

Quest Research Institute LLC

Farmington Hills, Michigan, 48334, United States

Location

Hassman Research Institute

Marlton, New Jersey, 08053, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Howard Hassman, MD

  Hassman Research Institute

  PRINCIPAL INVESTIGATOR

• Larry Blob, MD

  Cognitive Research Corporation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sentinel dosing will be employed for each cohort in Part A, with one subject randomized to receive IkT-148009 and the other placebo on the first day. These two subjects in each cohort will be monitored for 48 hours after dosing before deciding to dose the remainder of the cohort. As such, 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 sentinel pair in the next (higher dose) cohort, and each cohort will be dosed at approximately monthly intervals in order to allow adequate time for collection and review of safety and PK data. In Part B, 8 patients will be 3:1 randomized to placebo and dosed once per day for 7 days. In Part C, 8 patients will be 3:1 randomized to placebo and dosed once per day for 7 dayts.

Study Record Dates

• First Submitted: December 26, 2019
• First Posted: April 16, 2020
• Study Start: February 16, 2021
• Primary Completion: October 30, 2022
• Study Completion: January 30, 2023
• Last Updated: March 10, 2025

Record last verified: 2023-02

Locations

US (4)