Clinical trial NCT05483998: A Study to Evaluate Single and Multiple Doses of TLC-2716 in Healthy Participants
Official title: A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of TLC-2716 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: OrsoBio, Inc
Sponsor class: INDUSTRY
First posted: 2022-08-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Detailed description: This study is a randomized, placebo-controlled, sponsor-unblinded, and comprised of three parts: Part A (single-ascending dose), Part B (multiple-ascending dose), and Part C (adaptive single- and/or multiple-ascending dose).

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 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
* 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)
* 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/Exclusion criteria may apply.

Primary outcomes:
measure: Number of subjects with treatment-emergent adverse events (TEAEs) in single ascending dose (SAD) compared to placebo
timeFrame: Up to Day 15
measure: Number of subjects with clinically significant change from Baseline in vital signs in SAD
timeFrame: Day 1-Day 4, and Follow-up (after 11 days)
measure: Number of subjects with laboratory abnormalities in SAD
timeFrame: Up to 15 days
measure: Number of subjects with electrocardiogram (ECG) abnormalities in SAD
timeFrame: Up to 15 days
measure: Number of subjects with TEAEs in multiple ascending dose (MAD) compared to placebo
timeFrame: Up to Day 28
measure: Number of subjects with clinically significant change from Baseline in vital signs in MAD
timeFrame: Day 1 - Day 3, Day 5, Day 7, Day 10, Day 14, Day 17, and Follow-up (after 11 days)
measure: Number of subjects with laboratory abnormalities in MAD
timeFrame: Up to 28 days
measure: Number of subjects with ECG abnormalities in MAD
timeFrame: Up to 28 days
Secondary outcomes:
measure: Plasma concentration of each dose of study drug to determine AUClast in SAD
timeFrame: 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
measure: Plasma concentration of each dose of study drug to determine AUCinf in SAD
timeFrame: 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
measure: Plasma concentration of each dose of study drug to determine %AUCexp in SAD
timeFrame: 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
measure: Plasma concentration of each dose of study drug to determine CL/F in SAD
timeFrame: 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
measure: Plasma concentration of each dose of study drug to determine Cmax in SAD
timeFrame: 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
measure: Plasma concentration of each dose of study drug to determine Tmax in SAD
timeFrame: 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
measure: Plasma concentration of each dose of study drug to determine Clast in SAD
timeFrame: 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
measure: Plasma concentration of each dose of study drug to determine Tlast in SAD
timeFrame: 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
measure: Plasma concentration of each dose of study drug to determine t1/2 in SAD
timeFrame: 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
measure: Plasma concentration of each dose of study drug to determine λz in SAD
timeFrame: 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
measure: Plasma concentration of each dose of study drug to determine AUClast in MAD
timeFrame: Day 1, Day 3, Day 7, Day 14
measure: Plasma concentration of each dose of study drug to determine AUCtau in MAD
timeFrame: Day 1, Day 3, Day 7, Day 14
measure: Plasma concentration of each dose of study drug to determine Ctau in MAD
timeFrame: Day 1, Day 3, Day 7, Day 14
measure: Plasma concentration of each dose of study drug to determine CLss/F in MAD
timeFrame: Day 1, Day 3, Day 7, Day 14
measure: Plasma concentration of each dose of study drug to determine Cmax in MAD
timeFrame: Day 1, Day 3, Day 7, Day 14
measure: Plasma concentration of each dose of study drug to determine Tmax in MAD
timeFrame: Day 1, Day 3, Day 7, Day 14
measure: Plasma concentration of each dose of study drug to determine Clast in MAD
timeFrame: Day 1, Day 3, Day 7, Day 14
measure: Plasma concentration of each dose of study drug to determine Tlast in MAD
timeFrame: Day 1, Day 3, Day 7, Day 14
measure: Plasma concentration of each dose of study drug to determine t1/2 in MAD
timeFrame: Day 1, Day 3, Day 7, Day 14
measure: Plasma concentration of each dose of study drug to determine λz in MAD
timeFrame: Day 1, Day 3, Day 7, Day 14
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: OrsoBio Research Site
Study officials:
affiliation: OrsoBio, Inc
name: OrsoBio Study Director
role: STUDY_DIRECTOR
References: