Phase I, First-In-Human Study of TT-00920 in Healthy Subjects
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Pilot dose Cohort 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
Tablets
|
| Active Comparator: SAD Dose 1
|
Drug: TT-00920
Tablets
|
| Active Comparator: SAD Dose 2
|
Drug: TT-00920
Tablets
|
| Active Comparator: SAD Dose 3
|
Drug: TT-00920
Tablets
|
| Active Comparator: SAD Dose 4
|
Drug: TT-00920
Tablets
|
| Active Comparator: Food Effect Cohort
|
Drug: TT-00920
Tablets
|
| Placebo Comparator: Placebo
|
Drug: Placebos
Tablets
|
Outcome Measures
Primary Outcome Measures
- Numbers of Treatment Emergent Adverse Events(TEAE) [10 days]
Safety and tolerability of TT-00920
- Number of participants with Abnormal Laboratory Values [10 days]
Safety and tolerability of TT-00920
- Area under the plasma drug concentration versus time curve [10 days]
PK parameters of TT-00920
- Maximum Observed Plasma Concentration (Cmax) [10 days]
PK parameters of TT-00920
- Time of First Occurrence of Cmax （tmax) Time of first Occurance of Cmax（tmax) [10 days]
PK parameters of TT-00920
- Terminal half-life (t1/2) [10 days]
PK parameters of TT-00920
- Elimination rate (λz) [10 days]
PK parameters of TT-00920
- Volume of distribution (Vz/F) [10 days]
PK parameters of TT-00920
- Clearance (CL/F) [10 days]
PK parameters of TT-00920
Secondary Outcome Measures
- Area under the plasma drug concentration versus time curve [10 days]
the effect of food on the PK of TT-00920 following an oral dose
- Maximum Observed Plasma Concentration (Cmax) [10 days]
the effect of food on the PK of TT-00920 following an oral dose
- Time of first Occurance of Cmax（tmax) [10 days]
the effect of food on the PK of TT-00920 following an oral dose
- Terminal half-life (t1/2) [10 days]
the effect of food on the PK of TT-00920 following an oral dose
- Elimination rate (λz) [10 days]
the effect of food on the PK of TT-00920 following an oral dose
- Volume of distribution (Vz/F) [10 days]
the effect of food on the PK of TT-00920 following an oral dose
- Clearance (CL/F) [10 days]
the effect of food on the PK of TT-00920 following an oral dose
Other Outcome Measures
- Metabolite characterization in plasma and estimation of observed drug-related material in plasma to determine the presence of any metabolite >10% [10 days]
Exploratory outcome measures
- Cyclic guanosine monophosphate (cGMP) levels in plasma and urine [10days]
Exploratory outcome measures
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Early Phase Clinical Unit Glendale Adventist Medical Center | Los Angeles | California | United States | 91206 |
Sponsors and Collaborators
- TransThera Sciences (Nanjing), Inc.
Investigators
- Principal Investigator: Gevorkyan Hakop, MD, Early Phase Clinical Unit Glendale Adventist Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TT00920US01