Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TT5 | Experimental |
| |
| TT5 vehicle | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TT5 | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Adverse Events (AEs) and serious adverse events (SAEs) | Number of AEs and SAEs:To investigate the safety and tolerability of TT5 | SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14 |
| Clinically significant changes in physical examinations | % 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. | SAD cohorts: Baseline through Day 8; MAD cohorts: Baseline through Day 14 |
| Clinically significant changes in vital signs | % of participants with clinically significant change from baseline in vital signs by measuring heart rate, blood pressure, temperature, and respiratory rate | SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14 |
| Clinically significant changes in laboratory analysis | Mean and SD of clinically significant changes from baseline in laboratory analysis including hematology, coagulation, biochemistry, and urinalysis | SAD cohorts: Day-1 through Day 8; MAD cohorts: Day-1 through Day 14 |
| Bond and Lader Visual Analog Scale (VAS) | VAS item values: To assess vigilance will using a Visual Analogic Scale namely the Bond-Lader VAS of Mood and Alertness | SAD cohorts: Day 1 through Day 8; MAD cohorts: Day 1 through Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma AUC0-t measurement | Area under the concentration-time curve from time zero until the last observed concentration (AUC0-t) h*ng/ml | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| Plasma AUC0-inf measurement |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarkers | Fluid Biomarkers concentration (pmol/ml) | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
Main inclusion criteria for Parts A and B:
Main exclusion criteria for Parts A and B:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Olivier Blin, M.D., PhD | Contact | +33781637056 | Olivier.blin@tafalgie.fr |
| Name | Affiliation | Role |
|---|---|---|
| Guy Ludbrook, MD | University of Adelaide and Royal Adelaide Hospital. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cmax & PARC | Recruiting | Adelaide | South Australia | 5000 | Australia |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D010146 | Pain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo - TT5 vehicle | Drug | Intravenous administration of vehicule, according to the same drug regimen than TT5 |
|
Area under the concentration-time curve from time zero to infinity (AUC0-inf) h*ng/ml
| SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| Plasma Cmax measurement | Maximum concentration measurement in plasma (ng/ml) | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| Plasma Tmax measurement | Time to maximum observed concentration in plasma (hours) | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| Plasma T½ el measurement | Terminal elimination half-life (T½ el) in plasma (hours) | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| Plasma Kel measurement | Terminal elimination rate constant (Kel) in plasma (fraction/h) | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| Plasma Cl/F measurement | Apparent clearance (Cl/F) in plasma (mL/min) | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| Plasma Vz/F measurement | Apparent volume of distribution (Vz/F) in plasma (liters) | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| Urine CLr measurement | Renal clearance measurement in urine (mL/min) | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| Urine Aet1-t2 measurement | Amount excreted in urine (Aet1-t2) per interval (mL/min) | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| Urine Ae0-t measurement | Cumulative urinary excretion from time zero to time t (Ae0-t) ( (mL/min) | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| Urine Ae%dose measurement | % of drug recovered in urine (Ae%dose) | SAD cohorts: Day 1 through Day 2; MAD cohorts: Day 1 through Day 8 |
| ARCI | Total Score and Sub-scores of Addiction Research Center Inventory questionnaire to investigate subjective effects | SAD cohorts: Day 1 through Day 8; MAD cohorts: Day 1 through Day 14 |