A Study to Evaluate Single and Multiple Doses of TLC-2716 in Healthy Participants

NCT05483998 | Completed Phase 1

• 1 other identifier: 2716-CL-101
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1 study is designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TLC-2716 after single- and multiple-ascending doses in healthy subjects.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (8)

• Number of subjects with treatment-emergent adverse events (TEAEs) in single ascending dose (SAD) compared to placebo

  TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment.

  Up to Day 15

• Number of subjects with clinically significant change from Baseline in vital signs in SAD

  Vital signs include blood pressure, heart rate, respiratory rate, and temperature.

  Day 1-Day 4, and Follow-up (after 11 days)

• Number of subjects with laboratory abnormalities in SAD

  Hematology and serum chemistry.

  Up to 15 days

• Number of subjects with electrocardiogram (ECG) abnormalities in SAD

  12-lead ECG.

  Up to 15 days

• Number of subjects with TEAEs in multiple ascending dose (MAD) compared to placebo

  TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment.

  Up to Day 28

• Number of subjects with clinically significant change from Baseline in vital signs in MAD

  Vital signs include blood pressure, heart rate, respiratory rate, and temperature.

  Day 1 - Day 3, Day 5, Day 7, Day 10, Day 14, Day 17, and Follow-up (after 11 days)

• Number of subjects with laboratory abnormalities in MAD

  Hematology and serum chemistry.

  Up to 28 days

• Number of subjects with ECG abnormalities in MAD

  12-lead ECG

  Up to 28 days

Secondary Outcomes (20)

• Plasma concentration of each dose of study drug to determine AUClast in SAD

  Day 1: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 12, 24, 48, and 72 hours post-dose

• Plasma concentration of each dose of study drug to determine AUCinf in SAD

  Day 1: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 12, 24, 48, and 72 hours post-dose

• Plasma concentration of each dose of study drug to determine %AUCexp in SAD

  Day 1: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 12, 24, 48, and 72 hours post-dose

• Plasma concentration of each dose of study drug to determine CL/F in SAD

  Day 1: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 12, 24, 48, and 72 hours post-dose

• Plasma concentration of each dose of study drug to determine Cmax in SAD

  Day 1: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 12, 24, 48, and 72 hours post-dose

Study Arms (3)

Part A: Single Ascending Dose (SAD)

EXPERIMENTAL

Part A will be comprised of up to 50 participants over 5 cohorts of 10. Each participant will receive a single oral dose of TLC-2716 or placebo at different dose levels (1 cohort per dose level).

Drug: TLC-2716; Other: Placebo

Part B: Multiple Ascending Dose (MAD)

EXPERIMENTAL

Part B will be comprised of up to 50 healthy participants over 5 cohorts of 10. Each participant will receive 14 oral doses of TLC-2716 or placebo over 14 days (given once daily) at different dose levels (1 cohort per dose level).

Drug: TLC-2716; Other: Placebo

Part C: Adaptive SAD and/or MAD

EXPERIMENTAL

Part C is an adaptive style where the dosing level is a single- or multiple-ascending dose design. Based on safety and pharmacokinetic data from Parts A and B, doses for Part C will be chosen. Part C will be comprised of up to 50 participants over 5 cohorts of 10. Each participant will receive an oral dose of TLC-2716 or placebo at different dose levels (1 cohort per dose level).

Drug: TLC-2716; Other: Placebo

Interventions

TLC-2716 DRUG

TLC-2716

Part A: Single Ascending Dose (SAD); Part B: Multiple Ascending Dose (MAD); Part C: Adaptive SAD and/or MAD

Placebo OTHER

Placebo to match

Part A: Single Ascending Dose (SAD); Part B: Multiple Ascending Dose (MAD); Part C: Adaptive SAD and/or MAD

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Pregnant or lactating subjects
• Subjects with triglycerides ≥ 500 mg/dL
• Subjects with low-density lipoprotein ≥ 190 mg/dL
• 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

Sponsors & Collaborators

• OrsoBio, Inc: lead

Study Sites (1)

OrsoBio Research Site

Auckland, New Zealand

Location

Related Publications (1)

• Li X, Benegiamo G, Vijayakumar A, Sroda N, Kimura M, Huss RS, Weng S, Murakami E, Kirby BJ, von Alvensleben GVG, Kremoser C, Gane EJ, Takebe T, Myers RP, Subramanian GM, Auwerx J. An oral, liver-restricted LXR inverse agonist for dyslipidemia: preclinical development and phase 1 trial. Nat Med. 2026 Jan 16. doi: 10.1038/s41591-025-04169-6. Online ahead of print.

  PMID: 41545590 DERIVED

Study Officials

• OrsoBio Study Director

  OrsoBio, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Open to Sponsor
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: August 2, 2022
• Study Start: September 9, 2022
• Primary Completion: April 13, 2023
• Study Completion: June 18, 2023
• Last Updated: May 20, 2024

Record last verified: 2024-05

Locations

NZ (1)