Healthy Participants
Conditions
Brief summary
This phase 1 study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TLC-1180 after single- and multiple-ascending doses in healthy subjects.
Detailed description
The primary objectives are to assess the safety, tolerability, and plasma PK of TLC-1180 in healthy subjects. The exploratory objective is to evaluate the PD of TLC-1180 in healthy subjects. This study is comprised of four parts: Part A (single-ascending dose), Part B (multiple-ascending dose), optional Part C (adaptive single- and/or multiple-ascending dose), and Part D (relative bioavailability of a tablet formulation of TLC-1180). Up to 72, 100, 100, and 8 healthy subjects will be recruited in Parts A, B, C, and D, respectively. The effect of food on TLC-1180 PK will also be evaluated in this study.
Interventions
DRUGTLC-1180 Oral Solution
Oral solution of TLC-1180
DRUGTLC-1180 Tablet
Tablet formulation of TLC-1180
Placebo-to-match oral solution TLC-1180
OTHERPlacebo Tablet
Placebo-to-match tablet formulation of TLC-1180
Sponsors
OrsoBio, Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Non-smoking, healthy male or female subject between 18 and 55 years of age, inclusive * Body mass index from 19 to 35 kg/m2, inclusive * Estimated glomerular filtration rate ≥ 80 mL/min * Normal liver biochemistry tests * Screening laboratory evaluations (hematology, chemistry, and urinalysis) must fall within the normal range of the local laboratory's reference ranges unless the results have been determined by the investigator to have no clinical significance * Subject must have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator * Females of childbearing potential must have a negative pregnancy test at Screening and clinic admission * Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception * Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs
Exclusion criteria
* Pregnant or lactating subjects * Subjects who have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with the subject's treatment, assessment, or compliance with the protocol * Subjects who have received any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to study drug dosing * Current alcohol abuse that is judged by the investigator to potentially interfere with the subject's compliance or safety * Current substance abuse that is judged by the investigator to potentially interfere with the subject's compliance or safety * A positive test result for human immunodeficiency virus (HIV-1) antibody, hepatitis B (HBV) surface antigen, or hepatitis C (HCV) antibody * Subjects who have taken any prescription medications or over-the-counter medications, including herbal products, within 28 days prior to start of study drug dosing, with the exception of vitamins, acetaminophen (paracetamol), ibuprofen, and/or hormonal contraceptive medications * Subjects who have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to Screening or expected to receive these agents during the study (e.g., corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) * Medical history of serious skin disease in the opinion of the investigator, such as but not limited to rash, food allergy, eczema, psoriasis, or urticaria * Medical history of drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity) * Presence or history of cardiovascular disease, including significant cardiovascular disease (including a history of myocardial infarction based on ECG and/or clinical history), history of cardiac conduction abnormalities (including any history of ventricular tachycardia), congestive heart failure, cardiomyopathy with left ventricular ejection fraction \< 40%, a family history of Long QT Syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years * Syncope, palpitations, or unexplained dizziness * Implanted defibrillator or pacemaker * Medical history of liver disease, including but not limited to alcoholic liver disease, autoimmune disorders (e.g., primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency) * History of rhabdomyolysis * Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions * History of medical or surgical treatment that permanently alters intestinal absorption (e.g., gastric or intestinal surgery) * Subjects who have received vaccination for COVID-19 within 14 days of Admission Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of TLC-1180 treatment-emergent adverse events | Through study completion: Day 57 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study | Adverse events (AEs) - severity of the AEs will be graded using the Common Terminology Criteria for AE (CTCAE) (v5.0). The relationship between AEs and the study drug will be indicated as related or not related. |
| PK of TLC-1180 AUC | Through study completion: Day 57 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study | Area under the concentration-time curve |
| PK of TLC-1180 Cmax | Through study completion: Day 57 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study | Maximum plasma concentration |
| PK of TLC-1180 tmax | Through study completion: Day 57 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study | Time to reach Cmax |
| PK of TLC-1180 t1/2 | Through study completion: Day 57 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study | Half-life |
| PK of TLC-1180 CL/F | Through study completion: Day 57 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study | Apparent clearance, calculated as dose/AUC0-inf |
Countries
New Zealand
Contacts
CONTACTRyan Huss, MD
Outcome results
None listed