Pain
Conditions
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
Interventions
DRUGTT5
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
DRUGPlacebo - TT5 vehicle
Intravenous administration of vehicule, according to the same drug regimen than TT5
Sponsors
Tafalgie Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 Ae%dose measurement | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 | % of drug recovered in urine (Ae%dose) |
| 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) |
| 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 |
| 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) |
Countries
Australia
Contacts
CONTACTOlivier Blin, M.D., PhD
PRINCIPAL_INVESTIGATORGuy Ludbrook, MD
University of Adelaide and Royal Adelaide Hospital.
Outcome results
None listed