Clinical trial NCT06789861: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pain
Lead sponsor: Tafalgie Therapeutics
Sponsor class: INDUSTRY
First posted: 2025-01-23
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Primary outcomes:
measure: Incidence of Adverse Events (AEs) and serious adverse events (SAEs)
timeFrame: SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14
measure: Clinically significant changes in physical examinations
timeFrame: SAD cohorts: Baseline through Day 8; MAD cohorts: Baseline through Day 14
measure: Clinically significant changes in vital signs
timeFrame: SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14
measure: Clinically significant changes in laboratory analysis
timeFrame: SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14
measure: Bond and Lader Visual Analog Scale (VAS)
timeFrame: SAD cohorts: Day 1 through Day 8; MAD cohorts: Day 1 through Day 14
Secondary outcomes:
measure: Plasma AUC0-t measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: Plasma AUC0-inf measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: Plasma Cmax measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: Plasma Tmax measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: Plasma T½ el measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: Plasma Kel measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: Plasma Cl/F measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: Plasma Vz/F measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: Urine CLr measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: Urine Aet1-t2 measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: Urine Ae0-t measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: Urine Ae%dose measurement
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
measure: ARCI
timeFrame: SAD cohorts: Day 1 through Day 8; MAD cohorts: Day 1 through Day 14
Other outcomes:
measure: Biomarkers
timeFrame: SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8
Locations:
city: Adelaide
country: Australia
facility: Cmax & PARC
state: South Australia
Study officials:
affiliation: University of Adelaide and Royal Adelaide Hospital.
name: Guy Ludbrook, MD
role: PRINCIPAL_INVESTIGATOR
References: