Study to Assess the Safety and Pharmacokinetics of ATL-001 (Ciclopirox Olamine) in Healthy Volunteers

Study Overview
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Brief Summary
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The goal of this clinical trial is to assess the safety, tolerability and pharmacokinetics of ATL-001 (ciclopirox olamine) in healthy volunteers

Detailed Description
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Participants will receive either the investigational drug (ATL-001) or Placebo (inactive substance). Neither the participant nor the Investigator will know to which of these study drug groups each participant has been assigned. In case of an emergency, however, the Investigator can get this information. After a 30-day Screening period to confirm the eligibility, the prticipants will be treated for 5 days (the treatment period) and followed by 30 days of observation and assessment of treatment outcomes (the follow-up period).

Official Title
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A Phase I, Double-blind, Randomized, Placebo-controlled Study to Assess the Safety and Pharmacokinetics of ATL-001 (Ciclopirox Olamine) in Healthy Volunteers

Conditions
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Adverse Effect of Drugs and Medicaments in Therapeutic Use

Intervention / Treatment
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* Drug: Ciclopirox Olamine Oral
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects 18 to 65 years of age, inclusive Body mass index (BMI) within the range of 18.0 to 33.0 kg/m2, inclusive, and a minimum weight of at least 50.0 and maximum weight of 100.0 kg at Screening Estimated Glomerular Filtration Rate (eGFR) > 90 mL/min/1.73 m2 at Screening Female subjects of childbearing potential must be using and willing to continue using two medically acceptable contraceptive precautions from Screening and for at least 1 month after the last study drug administration. Medically acceptable forms of contraception include sexual abstinence [periodic abstinence (e.g., calendar, ovulation, symptothermal and post-ovulation methods) are not acceptable], combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), intrauterine devices (IUD), intrauterine hormone-releasing systems, and bilateral tubal ligation for subjects Female subjects of non-childbearing potential must be amenorrhoeic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy/salpingo-oophorectomy (as determined by subject medical history) Male subjects of reproductive potential with a partner(s) of childbearing potential must be using and willing to continue using two medically acceptable contraceptive precautions from Screening and for at least 1 month after the last study drug administration. Medically acceptable forms of contraception include abstinence, vasectomy, or male condom for subjects Female subjects must have a negative pregnancy test Must understand and provide written informed consent prior to the initiation of any protocol-specific procedures Must be willing and able to abide by all study requirements and restrictions Exclusion Criteria: Current drug or alcohol dependence (excluding caffeine), based on self-report, including subjects who have been in a drug rehabilitation program Current smoker or a history of using tobacco products within 3 months prior to Screening Clinically significant abnormalities on physical examination, medical history, 12-lead ECG (i.e., QTc > 440 ms for male subjects and > 450 ms for female subjects), vital signs, or laboratory values, as judged by the investigator or designee History or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results Use of a non-prescription drug within 14 days prior to the first drug administration. Subjects who have taken over-the-counter medication may still be entered into the study, if in the opinion of the investigator or designee, the medication received will not interfere with the study procedures or data integrity or compromise the safety of the subject Use of any prescription medications, recreational drugs, or natural health products (except vitamin or mineral supplements, acceptable forms of birth control, and hormone replacement) within 14 days prior to first drug administration or throughout the study, unless in the opinion of the investigator or designee, the product will not interfere with the study procedures or data integrity or compromise the safety of the subject Use of any medication that interfere with the glucuronidation metabolic pathway within 14 days prior to first drug administration Positive urine drug screen Positive breath alcohol test. If a subject presents with positive breath alcohol test, the subject may be rescheduled at the discretion of the investigator or designee Female subjects who are currently pregnant or lactating or who are planning to become pregnant within 60 days of last study drug administration Known history of allergy or hypersensitivity to any component of the active drug or placebo Positive for Hepatitis B, Hepatitis C, HIV or COVID-19 Treatment with any investigational drug within 30 days prior to first drug administration in the treatment phase A subject who, in the opinion of the investigator or designee, is not considered to be suitable and is unlikely to comply with the study protocol for any reason

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATL-001 0.2 mg/kg vs Placebo<br> | Drug: Ciclopirox Olamine Oral<br>* On the morning of Day 1 to Day 5, each participant will receive a single oral dose of ATL-001 or placebo<br>Other: Placebo<br>* On the morning of Day 1 to Day 5, each participant will receive a single oral dose of ATL-001 or placebo<br>|
| Experimental: ATL-001 0.5 mg/kg vs Placebo<br> | Drug: Ciclopirox Olamine Oral<br>* On the morning of Day 1 to Day 5, each participant will receive a single oral dose of ATL-001 or placebo<br>Other: Placebo<br>* On the morning of Day 1 to Day 5, each participant will receive a single oral dose of ATL-001 or placebo<br>|
| Experimental: ATL-001 1 mg/kg vs Placebo<br> | Drug: Ciclopirox Olamine Oral<br>* On the morning of Day 1 to Day 5, each participant will receive a single oral dose of ATL-001 or placebo<br>Other: Placebo<br>* On the morning of Day 1 to Day 5, each participant will receive a single oral dose of ATL-001 or placebo<br>|
| Experimental: ATL-001 2 mg/kg vs Placebo<br> | Drug: Ciclopirox Olamine Oral<br>* On the morning of Day 1 to Day 5, each participant will receive a single oral dose of ATL-001 or placebo<br>Other: Placebo<br>* On the morning of Day 1 to Day 5, each participant will receive a single oral dose of ATL-001 or placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | Incidence of adverse events (AEs) and of clinically relevant changes in vital signs values, electrocardiogram (ECG) data, physical examination and laboratory safety data for four different doses of ATL-001 | 3.5 months, with up to 66 days per participant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Derived pharmacokinetic parameters for ATL-001 | Area under the plasma drug concentration | 6 days per participant | 
| Derived pharmacokinetic parameters for ATL-001 | Time curve (AUC(0-last), AUC(0-12), AUC(0-24)) | 6 days per participant | 
| Derived pharmacokinetic parameters for ATL-001 | Maximum observed plasma drug concentration (Cmax) | 6 days per participant | 
| Derived pharmacokinetic parameters for ATL-001 | Time to maximum observed plasma drug concentration (tmax) | 6 days per participant | 
| Derived pharmacokinetic parameters for ATL-001 | Apparent terminal half-life (t1/2) | 6 days per participant | 
| Derived pharmacokinetic parameters for ATL-001 | Apparent total body clearance (CL/F) | 6 days per participant | 
| Derived pharmacokinetic parameters for ATL-001 | Apparent volume of distribution (Vz/F) | 6 days per participant |