A First in Human Study of TT5 in Single and Multiple Ascending Doses in Healthy Volunteers and Surgical Patients

Official title

A First in Human, Three-part, Double Blind, Randomized, Placebo-controlled, Single and Multiple Ascending Dose Study to Investigate Safety and Pharmacokinetics of TT5 in Healthy Participants and Surgical Patients

Overview

This study is a First in Human, three-parts, double-blind, randomized, placebo-controlled, single and multiple ascending dose study. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TT5 at different doses in healthy and surgical participants.

Detailed description

The study will be divided into three parts:

Part A: Single Ascending Dose - healthy participants cohorts with up to 5 dose levels.

Part B: Multiple Ascending Doses - healthy participants cohorts with up to 3 dose levels.

Part C: Surgical patients cohorts with up to 3 dose levels.

The primary Objective is to investigate the safety and tolerability of TT5 in single and multiple ascending intravenous doses in healthy participants and in surgical patients.

The Secondary Objectives are To investigate the pharmacokinetics (PK) of TT5 after single and multiple ascending intravenous doses in healthy participants and after intravenous doses in surgical patients.

* To investigate the acute and chronic psychological subjective response of the healthy participants and surgical patients to TT5 * To assess the pharmacodynamics (PD) of TT5 after intravenous doses in surgical patients. Exploratory Objectives areto explore potential fluid biomarkers for TT5

Interventions

• Drug TT5
  Direct Intravenous administration of TT5 (5 ascending doses in Single Ascending Dose Part and 3 ascending doses administered during 7 days in Multiple Ascending Dose Part in healthy volunteers) Direct Intravenous administration of TT5 in surgical patients (4 doses administered on the same day) in surgical patients
• Drug Placebo - TT5 vehicle
  Intravenous administration of vehicule, according to the same drug regimen than TT5

Primary outcome measures

• Incidence of Adverse Events (AEs) and serious adverse events (SAEs) [Time frame: SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14]
• Clinically significant changes in physical examinations [Time frame: SAD cohorts: Baseline through Day 8; MAD cohorts: Baseline through Day 14]
• Clinically significant changes in vital signs [Time frame: SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14]
• Clinically significant changes in laboratory analysis [Time frame: SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14]
• Bond and Lader Visual Analog Scale (VAS) [Time frame: SAD cohorts: Day 1 through Day 8; MAD cohorts: Day 1 through Day 14]

Secondary outcome measures (12)

• Plasma AUC0-t measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]
• Plasma AUC0-inf measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]
• Plasma Cmax measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]
• Plasma Tmax measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]
• Plasma T½ el measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]
• Plasma Kel measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]
• Plasma Cl/F measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]
• Plasma Vz/F measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]
• Urine CLr measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]
• Urine Aet1-t2 measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]
• Urine Ae0-t measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]
• Urine Ae%dose measurement [Time frame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8]

Eligibility criteria

Main inclusion criteria for Parts A and B:

• Non-smoker for the confinement period of the study.
• Medically healthy and without clinically significant abnormalities.
• Negative screen for alcohol and drugs of abuse.
• No history of psychiatric disorders.
• Female participants of non-childbearing potential must be post-menopausal or surgically sterile at least 3 months prior to dosing.
• Sexually active females of childbearing potential and non-sterile males must be willing to use an acceptable contraceptive method throughout the study.
• Able to understand the study procedures and provide signed informed consent to participate in the study in English.

Main exclusion criteria for Parts A and B:

• History of clinically significant asthma, anaphylaxis, major medical, psychiatric illness or surgery.
• Acute or chronic clinically relevant systemic disease or disorder.
• Renal insufficiency
• History of drug or alcohol consumption abuse.
• Drinking excessive amounts of tea, coffee, chocolate and/or beverage containing caffeine.
• Have used any investigational drug or participated in any clinical trial within 4 weeks prior to screening.
• Unable to refrain from strenuous exercise.
• Participant who has received blood or plasma derivatives, who had a surgery or who has given blood within 4 weeks prior to the screening visit or has planned to give blood or sperm within the 90 days following the study.
• Pregnant or lactating female participant.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Australia · 1 center

• Cmax & PARC — Adelaide

Identifiers

NCT: NCT06789861 · P-TT5-PH1-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗