Safety and Tolerability in Healthy Volunteers
Conditions
Keywords
Phase 1, TRT-448, Trotana
Brief summary
Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TRT-448 in Healthy Adult Subjects
Detailed description
This is a randomized, double-blind, placebo-controlled first-in-human (FIH) study of TRT-448 conducted in healthy adult participants. Key safety and tolerability assessments of TRT-448 will be regularly reviewed by an appointed Safety Review Committee (SRC). The study will be conducted in 2 parts: single ascending dose (SAD) and multiple ascending dose (MAD) healthy adult subject cohorts. Eligible subjects will be enrolled into a SAD cohort and will be randomized to receive a single dose of TRT-448 or placebo in a 3:1 ratio, respectively, via oral administration. Eligible participants will be enrolled into MAD cohorts and randomized to receive TRT-448 or placebo in a 3:1 ratio, respectively, once daily (QD) via oral administration from Day 1 and through Day 14 (MAD escalation cohorts) or from Day 1 through Day 28 (MAD expansion cohorts), inclusive. A total of up to 144 participants are planned to be enrolled. Each subject will be assessed for safety, pharmacokinetics and pharmacodynamics of TRT-448.
Interventions
DRUGTRT-448
Investigational drug modulates immune cells for the treatment of inflammatory disease
DRUGPlacebo
Inert placebo utilized as control
Sponsors
Trotana, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Medically healthy , as determined by pre-study medical history, and without clinically significant abnormalities * Adult males and females, 18 to 55 years of age (inclusive) at screening * Body mass index (BMI) between 18 and 32 kg/m2 (inclusive) with body weight: ≥ 70 kg for the SAD 1 cohort; ≥ 50 kg for all other cohorts * Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions
Exclusion criteria
* History of anaphylaxis or other significant allergy which would interfere with the volunteer's ability to participate in the study, including severe Types I-IV hypersensitivity reactions, cytokine release syndrome, or allergic reactions to multiple drugs * History or presence of cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal cholecystectomy, irritable bowel syndrome, inflammatory bowel disease, etc.), esophageal, endocrine, immunologic, autoimmune and/or inflammatory disease, dermatologic, psychiatric, or neurological disease/disorder * History of surgery or hospitalization within 3 months prior to screening, or surgery planned during the study. * Any history of malignant disease in the last 10 years, including leukemia, lymphoma or any significant hematology/oncology disease. Note: Participants with curatively resected non-melanoma skin cancers \>2 years prior to screening or curatively excised cervical carcinoma in situ \> 5 years prior to screening are not excluded. * Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia. * History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death or screening QTcF \> 450 msec in males or \> 470 msec in female) or a known arrhythmia (Note: asymptomatic first-degree heart block is not exclusionary). * Presence or having sequelae of gastrointestinal, liver (including Gilbert's syndrome), kidney, gallbladder, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. * Liver function test results elevated more than 1.3-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), bilirubin (total), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT). * Estimated glomerular filtration rate (eGFR) \< 80 mL/min/1.73m2 using the 2021 CKD-EPI creatinine equation. * Positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of TRT-448 in healthy participants | Day 1 to Day 28 | Incidence of treatment-emergent adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Day 1 to Day 28 | Maximum observed serum concentration |
| Tmax | Day 1 to Day 28 | Time to reach maximum observed serum concentration |
| AUClast | Day 1 to Day 28 | The area under the concentration-time curve from time zero to the time of the last observed quantifiable (non-zero) concentration |
| t1/2 | Day 1 to Day 28 | Apparent first-order terminal elimination half-life |
Contacts
CONTACTClinical Operations
Outcome results
None listed