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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pilot dose Cohort | Active Comparator | 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. |
|
| SAD Dose 1 | Active Comparator |
| |
| SAD Dose 2 | Active Comparator |
| |
| SAD Dose 3 | Active Comparator |
| |
| SAD Dose 4 | Active Comparator |
| |
| Food Effect Cohort | Active Comparator |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TT-00920 | Drug | Tablets |
|
| 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) |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Metabolite characterization in plasma and estimation of observed drug-related material in plasma to determine the presence of any metabolite >10% | Exploratory outcome measures | 10 days |
| Cyclic guanosine monophosphate (cGMP) levels in plasma and urine |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gevorkyan Hakop, MD | Early Phase Clinical Unit Glendale Adventist Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Early Phase Clinical Unit Glendale Adventist Medical Center | Los Angeles | California | 91206 | United States |
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Double (Paticipant, Investigator)
| Placebos | Drug | Tablets |
|
PK parameters of TT-00920
| 10 days |
| 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 |
Exploratory outcome measures
| 10days |