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

Phase 1

Recruiting

• Conditions: Pain
• Interventions: Drug: Placebo - TT5 vehicle; Drug: TT5

• Registration Number: NCT06789861
• Lead Sponsor: Tafalgie Therapeutics

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

Study Timeline

• Study First Submitted: 2025-01-09
• Study First Submitted QC: 2025-01-16
• Study First Posted: 2025-01-23
• Study Start: 2025-05-23
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-02
• Last Update Posted: 2025-06-03
• Primary Completion: 2025-09-29
• Study Completion: 2025-09-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 94

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TT5 vehicle	Placebo - TT5 vehicle	-
TT5	TT5	-

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse Events (AEs) and serious adverse events (SAEs)	SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14	Number of AEs and SAEs:To investigate the safety and tolerability of TT5
Clinically significant changes in physical examinations	SAD cohorts: Baseline through Day 8; MAD cohorts: Baseline through Day 14	% of participants with clinically significant changes from baseline in physical examinations by measuring general appearance, head, eyes, ears, nose, throat (HEENT), neck (including thyroid and nodes), cardiovascular, respiratory, gastrointestinal, renal, neurological, musculoskeletal, and skin.
Clinically significant changes in vital signs	SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14	% of participants with clinically significant change from baseline in vital signs by measuring heart rate, blood pressure, temperature, and respiratory rate
Clinically significant changes in laboratory analysis	SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14	Mean and SD of clinically significant changes from baseline in laboratory analysis including hematology, coagulation, biochemistry, and urinalysis
Bond and Lader Visual Analog Scale (VAS)	SAD cohorts: Day 1 through Day 8; MAD cohorts: Day 1 through Day 14	VAS item values: To assess vigilance will using a Visual Analogic Scale namely the Bond-Lader VAS of Mood and Alertness

Secondary Outcome Measures

Name	Time	Method
Plasma AUC0-t measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	Area under the concentration-time curve from time zero until the last observed concentration (AUC0-t) h\*ng/ml
Plasma AUC0-inf measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	Area under the concentration-time curve from time zero to infinity (AUC0-inf) h\*ng/ml
Plasma Cmax measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	Maximum concentration measurement in plasma (ng/ml)
Plasma Tmax measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	Time to maximum observed concentration in plasma (hours)
Plasma T½ el measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	Terminal elimination half-life (T½ el) in plasma (hours)
Plasma Kel measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	Terminal elimination rate constant (Kel) in plasma (fraction/h)
Plasma Cl/F measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	Apparent clearance (Cl/F) in plasma (mL/min)
Plasma Vz/F measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	Apparent volume of distribution (Vz/F) in plasma (liters)
Urine CLr measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	Renal clearance measurement in urine (mL/min)
Urine Aet1-t2 measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	Amount excreted in urine (Aet1-t2) per interval (mL/min)
Urine Ae0-t measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	Cumulative urinary excretion from time zero to time t (Ae0-t) ( (mL/min)
Urine Ae%dose measurement	SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8	% of drug recovered in urine (Ae%dose)
ARCI	SAD cohorts: Day 1 through Day 8; MAD cohorts: Day 1 through Day 14	Total Score and Sub-scores of Addiction Research Center Inventory questionnaire to investigate subjective effects

Trial Locations

Locations (1)

Cmax & PARC; 🇦🇺 Adelaide, South Australia, Australia