A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of TLC-1180 in Healthy Subjects and an Open-Label Assessment of the Relative Bioavailability of, and Effect of Food on, a Tablet Formulation of TLC-1180
Overview
- Phase
- Phase 1
- Intervention
- TLC-1180 Oral Solution
- Conditions
- Not specified
- Sponsor
- OrsoBio, Inc
- Enrollment
- 288
- Locations
- 1
- Primary Endpoint
- Incidence of TLC-1180 treatment-emergent adverse events
- Status
- Recruiting
- Last Updated
- 18 days ago
Overview
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.
Investigators
Eligibility Criteria
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)
Arms & Interventions
Oral Solution
Oral solution of TLC-1180
Intervention: TLC-1180 Oral Solution
Oral Solution
Oral solution of TLC-1180
Intervention: Placebo Oral Solution
Tablet
Tablet formulation of TLC-1180
Intervention: Placebo Tablet
Tablet
Tablet formulation of TLC-1180
Intervention: TLC-1180 Tablet
Outcomes
Primary Outcomes
Incidence of TLC-1180 treatment-emergent adverse events
Time Frame: Through study completion: Day 365 (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
Time Frame: Through study completion: Day 365 (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
Time Frame: Through study completion: Day 365 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study
Maximum plasma concentration
PK of TLC-1180 tmax
Time Frame: Through study completion: Day 365 (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
Time Frame: Through study completion: Day 365 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study
Half-life
PK of TLC-1180 CL/F
Time Frame: Through study completion: Day 365 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study
Apparent clearance, calculated as dose/AUC0-inf
Incidence of TLC-1180 treatment-emergent adverse events
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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