Clinical trial NCT04364789: Phase I, First-In-Human Study of TT-00920 in Healthy Subjects
Official title: A Phase I, First-In-Human, Randomized, Double-blind, Placebo-controlled, Single-Ascending-Dose Study of TT-00920 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: TransThera Sciences (Nanjing), Inc.
Sponsor class: INDUSTRY
First posted: 2020-04-28
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Numbers of Treatment Emergent Adverse Events(TEAE)
timeFrame: 10 days
measure: Number of participants with Abnormal Laboratory Values
timeFrame: 10 days
measure: Area under the plasma drug concentration versus time curve
timeFrame: 10 days
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 10 days
measure: Time of First Occurrence of Cmax （tmax) Time of first Occurance of Cmax（tmax)
timeFrame: 10 days
measure: Terminal half-life (t1/2)
timeFrame: 10 days
measure: Elimination rate (λz)
timeFrame: 10 days
measure: Volume of distribution (Vz/F)
timeFrame: 10 days
measure: Clearance (CL/F)
timeFrame: 10 days
Secondary outcomes:
measure: Area under the plasma drug concentration versus time curve
timeFrame: 10 days
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 10 days
measure: Time of first Occurance of Cmax（tmax)
timeFrame: 10 days
measure: Terminal half-life (t1/2)
timeFrame: 10 days
measure: Elimination rate (λz)
timeFrame: 10 days
measure: Volume of distribution (Vz/F)
timeFrame: 10 days
measure: Clearance (CL/F)
timeFrame: 10 days
Other outcomes:
measure: Metabolite characterization in plasma and estimation of observed drug-related material in plasma to determine the presence of any metabolite >10%
timeFrame: 10 days
measure: Cyclic guanosine monophosphate (cGMP) levels in plasma and urine
timeFrame: 10days
Locations:
city: Los Angeles
country: United States
facility: Early Phase Clinical Unit Glendale Adventist Medical Center
state: California
Study officials:
affiliation: Early Phase Clinical Unit Glendale Adventist Medical Center
name: Gevorkyan Hakop, MD
role: PRINCIPAL_INVESTIGATOR
References: