A Study to Assess Single and Multiple Doses of IkT-148009 in Healthy Elderly Participants and Parkinson's Patients
Condition: Healthy Elderly; Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 1

Summary: 
      This study investigates the safety and tolerability of drug IkT-148009 in healthy elderly
      volunteers (55 to 70 years old). It also looks at the movement of IkT-148009 in the body.
      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 capsules.

      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.

      If Part A clinical exposure and PK data through 2 or more cohorts raise no concerns to the
      SRC, Part B may commence at the discretion of the SRC while the remaining Part A cohorts are
      completed.

      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).
    

Intervention name(s): IkT-148009; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oral administration gelatin capsule; Oral administration gelatin capsule
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: 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.
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science