A Phase I Clinical Trial to Investigate the Safety, Tolerability, and Pharmacokinetic Characteristics of TT-01025-CL in Healthy Subjects

Study Overview
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Brief Summary
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To assess the safety, tolerability and pharmacokinetic characteristics of TT-01025 in healthy male subjects

Official Title
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A Phase I, First-In-Human, Randomized, Double Blind, Placebo Controlled, Single Ascending-Dose and Multi Ascending Dose Study of TT-01025-CL in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: TT-01025-CL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Age ≥ 18 years and ≤ 55 years, male or female. Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and weighs at least 50 kg. No clinically significant findings in medical examination, including physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory tests. Male participant and his female spouse/partner who is of childbearing potential agree to use highly effective contraception* consisting of two forms of birth control (at least one of which must be a barrier method) from signing of informed consent throughout the study period and for 90 days after final study drug administration. A female subject of childbearing potential who is sexually active agrees to use highly effective contraception* consisting of two forms of birth control (at least one of which must be a barrier method) from signing of informed consent throughout the duration of the study period and for 90 days after last study drug administration. If the next menstrual period is delayed, a pregnancy test will be required for exclusion of pregnancy. Highly effective contraception is defined as: Established use of oral, injected, or implanted hormonal methods of contraception Placement of an intrauterine device or intrauterine system Barrier methods of contraception: condom with spermicidal foam, gel, film, cream, suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, cream, or suppository Able to understand and sign informed consent and to comply with the protocol Exclusion Criteria: Any history of clinically serious disease. Any active or unstable clinically significant medical condition as judged by the investigator. Subject has abnormal Screening findings or Day -2 laboratory value that suggest a clinically significant underlying disease. Hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes. Received any investigational drug within 30 days or 5x T1/2 whichever is longer before the Screening. Participants who have undergone major surgery ≤ 2 months prior to start study drug. Impaired cardiac function including clinically significant arrhythmias or clinically significant abnormality in clinical test, including but not limited to any of the following at Screening and Check-in, repeat testing is allowed for verification, at the discretion of the Investigator: Heart rate < 45 beats per minute (bpm) or > 90 bpm (taken during blood pressure measurement). Systolic blood pressure (SBP) < 90 mmHg or > 140 mmHg; diastolic blood pressure (DBP) < 50 mmHg or > 90 mmHg. Average of the 3 QT intervals corrected using Fridericia's formula (QTcF) > 450 milliseconds. Second degree or higher Atrioventricular block on ECG Estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2 Impaired renal function or abnormal liver enzymes at baseline, including but not limited to: Alanine aminotransferase (ALT) > upper limit of normal (ULN) Aspartate aminotransferase (AST) > ULN Estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2 Women who are pregnant or lactating, or intending to become pregnant before, during or within 90 days after exit from this study. Women with baseline FSH ≥40mIU/ml Participant who has had a loss of more than 100 mL blood (e.g., a blood donation) within 2 months before study drug administration, or has received any blood, plasma, or platelet transfusions within 3 months before Check-in, or plans to donate blood, ova or sperm during the study or within 3 months after the study. Participant who has a known history of, or a positive test result for, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) types 1 or 2 at screening. Participant who has used prescription or over-the-counter (OTC) medication (other than ≤2 g/day paracetamol [acetaminophen] or ≤800 mg/day ibuprofen), vitamins, or herbal remedies, within 7 days or 5 half-lives before study drug administration, whichever is longer. Participant who has a history of alcohol abuse (defined as an alcohol intake more than 21 units per week) or a history of drug abuse within the 6 months before study drug administration, or a history of substance abuse deemed significant by the investigator. A unit of alcohol is defined as 240 mL of beer, 120 mL of wine, or 20 mL of spirits. Participant who smokes cigarettes or uses other nicotine-containing products (e.g., vape, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers), has done so in the 3 months prior to screening. Consumption of caffeine or xanthine-containing food or beverages from at least 72 hours prior to Check-in to the clinical research unit until at least 24 hours after last drug administration Participant who has a positive test for alcohol or drugs of abuse (amphetamines, barbiturates, benzodiazepines, MDMA, oxycodone, phencyclidine, methamphetamine, tricyclic antidepressants, opiates, methadone, cocaine, cannabinoids, amphetamines, or cotinine) at Screening or Check-in. Subject is unable to complete this study for other reasons or the Investigator believes that he or she should be excluded. Participant who has a positive swab test of COVID-19 from Screening or Check-in testing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug: TT-01025-CL<br>TT-01025-CL | Drug: TT-01025-CL<br>* Oral tablet<br>|
| Placebo Comparator: Drug: Placebo<br>Placebo of TT-01025-CL | Drug: TT-01025-CL<br>* Oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax |  | up to 7 days post-dose | 
| AUC |  | up to 7 days post-dose | 
| Terminal half-life |  | up to 7 days post-dose |