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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: TT-00920; Drug: Placebos

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 Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 91206
      • Early Phase Clinical Unit Glendale Adventist Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebos; Tablets
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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	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	Exploratory outcome measures	10days

Collaborators and Investigators

• Sponsor: TransThera Sciences (Nanjing), Inc.
• Investigators: Principal Investigator: Gevorkyan Hakop, MD, Early Phase Clinical Unit Glendale Adventist Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2020
• Primary Completion (Actual): June 18, 2021
• Study Completion (Actual): March 17, 2022

Study Registration Dates

• First Submitted: April 21, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 24, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: TT00920US01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No