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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05483998




Registration number
NCT05483998
Ethics application status
Date submitted
27/07/2022
Date registered
2/08/2022
Date last updated
20/05/2024

Titles & IDs
Public title
A Study to Evaluate Single and Multiple Doses of TLC-2716 in Healthy Participants
Scientific 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
Secondary ID [1] 0 0
2716-CL-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Subjects 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TLC-2716
Other interventions - Placebo

Experimental: Part A: Single Ascending Dose (SAD) - 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).

Experimental: Part B: Multiple Ascending Dose (MAD) - 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).

Experimental: Part C: Adaptive SAD and/or MAD - 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).


Treatment: Drugs: TLC-2716
TLC-2716

Other interventions: Placebo
Placebo to match
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects with treatment-emergent adverse events (TEAEs) in single ascending dose (SAD) compared to placebo
Timepoint [1] 0 0
Up to Day 15
Primary outcome [2] 0 0
Number of subjects with clinically significant change from Baseline in vital signs in SAD
Timepoint [2] 0 0
Day 1-Day 4, and Follow-up (after 11 days)
Primary outcome [3] 0 0
Number of subjects with laboratory abnormalities in SAD
Timepoint [3] 0 0
Up to 15 days
Primary outcome [4] 0 0
Number of subjects with electrocardiogram (ECG) abnormalities in SAD
Timepoint [4] 0 0
Up to 15 days
Primary outcome [5] 0 0
Number of subjects with TEAEs in multiple ascending dose (MAD) compared to placebo
Timepoint [5] 0 0
Up to Day 28
Primary outcome [6] 0 0
Number of subjects with clinically significant change from Baseline in vital signs in MAD
Timepoint [6] 0 0
Day 1 - Day 3, Day 5, Day 7, Day 10, Day 14, Day 17, and Follow-up (after 11 days)
Primary outcome [7] 0 0
Number of subjects with laboratory abnormalities in MAD
Timepoint [7] 0 0
Up to 28 days
Primary outcome [8] 0 0
Number of subjects with ECG abnormalities in MAD
Timepoint [8] 0 0
Up to 28 days
Secondary outcome [1] 0 0
Plasma concentration of each dose of study drug to determine AUClast in SAD
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Plasma concentration of each dose of study drug to determine AUCinf in SAD
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Plasma concentration of each dose of study drug to determine %AUCexp in SAD
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Plasma concentration of each dose of study drug to determine CL/F in SAD
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Plasma concentration of each dose of study drug to determine Cmax in SAD
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Plasma concentration of each dose of study drug to determine Tmax in SAD
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Plasma concentration of each dose of study drug to determine Clast in SAD
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
Plasma concentration of each dose of study drug to determine Tlast in SAD
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
Plasma concentration of each dose of study drug to determine t1/2 in SAD
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
Plasma concentration of each dose of study drug to determine ?z in SAD
Timepoint [10] 0 0
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
Secondary outcome [11] 0 0
Plasma concentration of each dose of study drug to determine AUClast in MAD
Timepoint [11] 0 0
Day 1, Day 3, Day 7, Day 14
Secondary outcome [12] 0 0
Plasma concentration of each dose of study drug to determine AUCtau in MAD
Timepoint [12] 0 0
Day 1, Day 3, Day 7, Day 14
Secondary outcome [13] 0 0
Plasma concentration of each dose of study drug to determine Ctau in MAD
Timepoint [13] 0 0
Day 1, Day 3, Day 7, Day 14
Secondary outcome [14] 0 0
Plasma concentration of each dose of study drug to determine CLss/F in MAD
Timepoint [14] 0 0
Day 1, Day 3, Day 7, Day 14
Secondary outcome [15] 0 0
Plasma concentration of each dose of study drug to determine Cmax in MAD
Timepoint [15] 0 0
Day 1, Day 3, Day 7, Day 14
Secondary outcome [16] 0 0
Plasma concentration of each dose of study drug to determine Tmax in MAD
Timepoint [16] 0 0
Day 1, Day 3, Day 7, Day 14
Secondary outcome [17] 0 0
Plasma concentration of each dose of study drug to determine Clast in MAD
Timepoint [17] 0 0
Day 1, Day 3, Day 7, Day 14
Secondary outcome [18] 0 0
Plasma concentration of each dose of study drug to determine Tlast in MAD
Timepoint [18] 0 0
Day 1, Day 3, Day 7, Day 14
Secondary outcome [19] 0 0
Plasma concentration of each dose of study drug to determine t1/2 in MAD
Timepoint [19] 0 0
Day 1, Day 3, Day 7, Day 14
Secondary outcome [20] 0 0
Plasma concentration of each dose of study drug to determine ?z in MAD
Timepoint [20] 0 0
Day 1, Day 3, Day 7, Day 14

Eligibility
Key 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
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/09/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/06/2023
Sample size
Target
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
OrsoBio, Inc
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05483998
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
OrsoBio Study Director
Address 0 0
OrsoBio, Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries