Phase I, First-In-Human Study of TT-00920 in Healthy Subjects

Study Overview
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Brief Summary
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This is a first-in-human, randomized, double-blind, placebo-controlled study. The primary objectives of the study were to investigate the safety and tolerability and determine the PK profiles of single ascending doses (SAD) of TT-00920 administered to healthy subjects. The secondary objectives of the study were to assess the effect of food on the PK of TT-00920 following an oral dose.

Detailed Description
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There will be 4 single-ascending-dose cohorts and 1 cohort for food effect assessment to assess the safety, tolerability, and PK profile. A pilot dose of 20 mg will be evaluated in 2 subjects (all receiving TT-00920) for safety, tolerability, and PK profile before the initiation of dose escalation. In single-ascending-dose cohorts, 8 subjects per cohort will be enrolled and randomized to assess the safety, tolerability, and PK profile. In food effect cohort, there will be 8 subjects (all receiving TT-00920). Subjects in food effect cohort will receive 2 single dose periods (Fasted/ Fed) in an open-label, crossover design.

Official Title
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A Phase I, First-In-Human, Randomized, Double-blind, Placebo-controlled, Single-Ascending-Dose Study of TT-00920 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: TT-00920
* Drug: Placebos


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 of non-childbearing potential (confirmed with follicle stimulating hormone [FSH] test. A bilateral tubal ligation is acceptable as long as there is no fertility potential). Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and weighs at least 50 kg. No clinically significant findings in medical examination Exclusion Criteria: Any history of clinically serious disease. Hypersensitivity or allergy to any of the study drugs or drugs of similar chemical classes. Impaired cardiac function including clinically significant arrhythmias or clinically significant abnormality in clinical test Subject with a history of severe visual diseases; or visual changes including flushing lights, blurry vision, color changes, or other visual changes; or abnormal finding with visual tests [color discrimination (Ishihara test) and visual acuity (Snellen chart). Subject is unable to complete this study for other reasons or the Investigator believes that he or she should be excluded.

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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pilot dose Cohort<br>A pilot dose of 20 mg will be evaluated in 2 subjects (all receiving TT-00920) for safety, tolerability, and PK profile before the initiation of dose escalation. | Drug: TT-00920<br>* Tablets<br>|
| Active Comparator: SAD Dose 1<br> | Drug: TT-00920<br>* Tablets<br>|
| Active Comparator: SAD Dose 2<br> | Drug: TT-00920<br>* Tablets<br>|
| Active Comparator: SAD Dose 3<br> | Drug: TT-00920<br>* Tablets<br>|
| Active Comparator: SAD Dose 4<br> | Drug: TT-00920<br>* Tablets<br>|
| Active Comparator: Food Effect Cohort<br> | Drug: TT-00920<br>* Tablets<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebos<br>* Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numbers of Treatment Emergent Adverse Events(TEAE) | Safety and tolerability of TT-00920 | 10 days | 
| Number of participants with Abnormal Laboratory Values | Safety and tolerability of TT-00920 | 10 days | 
| Area under the plasma drug concentration versus time curve | PK parameters of TT-00920 | 10 days | 
| Maximum Observed Plasma Concentration (Cmax) | PK parameters of TT-00920 | 10 days | 
| Time of First Occurrence of Cmax （tmax) Time of first Occurance of Cmax（tmax) | PK parameters of TT-00920 | 10 days | 
| Terminal half-life (t1/2) | PK parameters of TT-00920 | 10 days | 
| Elimination rate (λz) | PK parameters of TT-00920 | 10 days | 
| Volume of distribution (Vz/F) | PK parameters of TT-00920 | 10 days | 
| Clearance (CL/F) | PK parameters of TT-00920 | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma drug concentration versus time curve | the effect of food on the PK of TT-00920 following an oral dose | 10 days | 
| Maximum Observed Plasma Concentration (Cmax) | the effect of food on the PK of TT-00920 following an oral dose | 10 days | 
| Time of first Occurance of Cmax（tmax) | the effect of food on the PK of TT-00920 following an oral dose | 10 days | 
| Terminal half-life (t1/2) | the effect of food on the PK of TT-00920 following an oral dose | 10 days | 
| Elimination rate (λz) | the effect of food on the PK of TT-00920 following an oral dose | 10 days | 
| Volume of distribution (Vz/F) | the effect of food on the PK of TT-00920 following an oral dose | 10 days | 
| Clearance (CL/F) | the effect of food on the PK of TT-00920 following an oral dose | 10 days |