A Phase I Study of Single and Multiple Doses of VG290131 in Healthy Subjects

NCT06081465 | Recruiting Phase 1

• 1 other identifier: VG290131-AU-001
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled phase I study to evaluate the safety, tolerability and PK profiles of orally administered VG290131 in healthy subjects. The main questions it aims to answer are:

1. 1.The safety and tolerability of VG290131 when administered orally as a single dose and multiple doses in healthy subjects.
2. 2.The pharmacokinetic (PK) profiles of VG290131 and the food effect on the PK profiles of VG290131 in healthy subjects.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (5)

• To evaluate the safety and tolerability of VG290131 by TEAEs

  To evaluate the safety and tolerability of VG290131 after SAD and MAD doses to healthy volunteers by assessing the incidence, severity, and causality of treatment-emergent adverse events (TEAEs).

  From admission to discharge, up to 12 days.

• To evaluate the safety and tolerability of VG290131 by 12-Lead ECG

  To evaluate the safety and tolerability of VG290131 after SAD and MAD doses to healthy volunteers by assessing the number and percentage of subjects with clinically significant changes in 12-Lead ECG (RR, PR, QRSD, QT, and QTc).

  From admission to discharge, up to 12 days.

• To evaluate the safety and tolerability of VG290131 by vital signs

  To evaluate the safety and tolerability of VG290131 after SAD and MAD doses to healthy volunteers by assessing the number and percentage of subjects with clinically significant changes in vital signs (Blood pressure, heart rate, body temperature, and respiration rate).

  From admission to discharge, up to 12 days.

• To evaluate the safety and tolerability of VG290131 by physical examinations

  To evaluate the safety and tolerability of VG290131 after SAD and MAD doses to healthy volunteers by assessing the number and percentage of subjects with clinically significant changes in physical examinations (Skin and mucosa, lymph nodes, head, eyes, ears, nose, and throat (HEENT), chest, abdomen, spine and limbs, musculoskeletal system, and nervous system).

  From admission to discharge, up to 12 days.

• To evaluate the safety and tolerability of VG290131 by clinical laboratory tests

  To evaluate the safety and tolerability of VG290131 after SAD and MAD doses to healthy volunteers by assessing the number and percentage of subjects with clinically significant changes in clinical laboratory tests (hematology, coagulation, biochemistry and urine analysis).

  From admission to discharge, up to 12 days.

Secondary Outcomes (14)

• To evaluate PK parameter Cmax of VG290131 after a single dose

  From admission to discharge, up to 12 days.

• To evaluate PK parameter Tmax of VG290131 after a single dose

  From admission to discharge, up to 12 days.

• To evaluate PK parameter AUC0-t of VG290131 after a single dose

  From admission to discharge, up to 12 days.

• To evaluate PK parameter AUC0-inf of VG290131 after a single dose

  From admission to discharge, up to 12 days.

• To evaluate PK parameter t1/2 of VG290131 after a single dose

  From admission to discharge, up to 12 days.

Study Arms (10)

SAD Cohort 1

EXPERIMENTAL

In SAD Cohort 1, 8 subjects will be randomized to receive a single dose of VG290131 (1 mg) (n=6) or matching placebo (n=2), respectively. To ensure the safety of the subjects, two sentinel subjects will be enrolled first: one subject will be randomized to receive VG290131, and the other subject will be randomized to receive a placebo. After the investigator reviews safety/tolerability information available on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in the cohort will be randomized to receive VG290131 (n=5) and placebo (n=1).

Drug: VG290131

SAD Cohort 2 (FE Study)

EXPERIMENTAL

SAD Cohort 2 (FE study) is a two-sequence, two-period crossover study. A total of 14 healthy subjects will be randomized to two dosing sequences in a 1:1 ratio. Subjects in sequence 1 will receive a single dose of VG290131 (5 mg) or placebo under fasted condition in Period 1 and under fed condition in Period 2. Subjects in sequence 2 will be administered under fed condition in Period 1 and under fasted condition in Period 2. There will be a 7-day washout between the two dosing periods. Two sentinel subjects will be enrolled in the two dosing sequences of Period 1, respectively: one subject will be randomized to receive VG290131 (5 mg), and the other subject will be randomized to receive placebo. After the investigator reviews safety/tolerability information on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in that sequences will be randomized to receive VG290131 (n=4) and placebo (n=1). No sentinel subjects in Period 2.

Drug: VG290131

SAD Cohort 3

EXPERIMENTAL

In SAD Cohort 3, 8 subjects will be randomized to receive a single dose of VG290131 (25 mg) (n=6) or matching placebo (n=2), respectively. To ensure the safety of the subjects, two sentinel subjects will be enrolled first: one subject will be randomized to receive VG290131, and the other subject will be randomized to receive a placebo. After the investigator reviews safety/tolerability information available on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in the cohort will be randomized to receive VG290131 (n=5) and placebo (n=1).

Drug: VG290131

SAD Cohort 4

EXPERIMENTAL

In SAD Cohort 4, 8 subjects will be randomized to receive a single dose of VG290131 (50 mg) (n=6) or matching placebo (n=2), respectively. To ensure the safety of the subjects, two sentinel subjects will be enrolled first: one subject will be randomized to receive VG290131, and the other subject will be randomized to receive a placebo. After the investigator reviews safety/tolerability information available on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in the cohort will be randomized to receive VG290131 (n=5) and placebo (n=1).

Drug: VG290131

SAD Cohort 5

EXPERIMENTAL

In SAD Cohort 5, 8 subjects will be randomized to receive a single dose of VG290131 (100 mg) (n=6) or matching placebo (n=2), respectively. To ensure the safety of the subjects, two sentinel subjects will be enrolled first: one subject will be randomized to receive VG290131, and the other subject will be randomized to receive a placebo. After the investigator reviews safety/tolerability information available on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in the cohort will be randomized to receive VG290131 (n=5) and placebo (n=1).

Drug: VG290131

SAD Cohort 6

EXPERIMENTAL

In SAD Cohort 6, 8 subjects will be randomized to receive a single dose of VG290131 (200 mg) (n=6) or matching placebo (n=2), respectively. To ensure the safety of the subjects, two sentinel subjects will be enrolled first: one subject will be randomized to receive VG290131, and the other subject will be randomized to receive a placebo. After the investigator reviews safety/tolerability information available on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in the cohort will be randomized to receive VG290131 (n=5) and placebo (n=1).

Drug: VG290131

MAD Cohort 1

EXPERIMENTAL

In MAD Cohort 1, 8 subjects will be randomized 3:1 to receive a once or twice daily dose of VG290131 (1 mg) (n=6) or matching placebo (n=2) for 7 consecutive days depending on the PK profiles of the SAD study, respectively.

Drug: VG290131

MAD Cohort 2

EXPERIMENTAL

In MAD Cohort 1, 8 subjects will be randomized 3:1 to receive a once or twice daily dose of VG290131 (5 mg) (n=6) or matching placebo (n=2) for 7 consecutive days depending on the PK profiles of the SAD study, respectively.

Drug: VG290131

MAD Cohort 3

EXPERIMENTAL

In MAD Cohort 1, 8 subjects will be randomized 3:1 to receive a once or twice daily dose of VG290131 (25 mg) (n=6) or matching placebo (n=2) for 7 consecutive days depending on the PK profiles of the SAD study, respectively.

Drug: VG290131

MAD Cohort 4

EXPERIMENTAL

In MAD Cohort 1, 8 subjects will be randomized 3:1 to receive a once or twice daily dose of VG290131 (100 mg) (n=6) or matching placebo (n=2) for 7 consecutive days depending on the PK profiles of the SAD study, respectively.

Drug: VG290131

Interventions

VG290131 DRUG

The study drug and matching placebo will be administered orally.

MAD Cohort 1; MAD Cohort 2; MAD Cohort 3; MAD Cohort 4; SAD Cohort 1; SAD Cohort 2 (FE Study); SAD Cohort 3; SAD Cohort 4; SAD Cohort 5; SAD Cohort 6

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing to comply with protocol required visit schedule and visit requirements and provide written ICF;
• Healthy adult male and female subjects, aged 18 to 45 years of age (inclusive) at the time of signing the ICF;
• Body mass index between 18.0 and 32.0 kg/m2, inclusive;
• Considered medically healthy as determined by the investigator, based on medical history and clinical evaluations including physical examination, clinical laboratory tests, vital sign measurements, and 12-Lead ECG;
• Male subjects must agree to practice true abstinence; be surgically sterilized (performed at least 6 months prior to screening and documented to no longer produce sperm - verbal confirmation through medical history review acceptable); or agree to use a condom plus effective contraception methods for their female partner, if of childbearing potential, from the signing of ICF to 3 months after the last dose of IMPs and refrain from donating sperm during this period. These contraception requirements do not apply if the male subject is in an exclusively same sex relationship;
• Female subjects are eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
• Women of non-childbearing potential (WONCBP), defined as surgically sterile (hysterectomy, bilateral salpingectomy, bilateral tubal ligation or bilateral oophorectomy - verbal confirmation through medical history review acceptable) or postmenopausal (no menses for 12 months and confirmed by follicle stimulating hormone \[FSH\] level ≥40 mlU/mL);
• WOCBP and agree to practice true abstinence or agrees to use a highly effective method of contraceptions consistently from the signing of ICF to 3 months after the last dose of investigational medicinal products \[IMPs\] and refrain from donating eggs during this period. And WOCBP must have a negative serum and/or urine pregnancy test result within 7 days prior to the first dose of IMPs.
• Subject is in an exclusively same-sex relationship.

You may not qualify if:

• Ascertained or presumptive hypersensitivity (including allergies) to any ingredient of the VG290131; history of other significant allergies or anaphylaxis, as determined by the investigator;
• Considered by the investigator to be ineligible for the study due to a history of or current condition of significant metabolic or endocrine, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, immunological, neurological, or psychiatric disorders with clinical manifestations;
• Active or history of serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression, which require current pharmacological intervention;
• History of stomach or intestinal surgery or resection diseases including but not limited to, gastric band/gastric resection and/or intestinal resection and/or duodenal disease (i.e. celiac disease) which may potentially alter absorption and/or excretion of VG290131 (except for an appendectomy);
• Used drugs or substances known to be inducers or inhibitors of cytochrome P450 enzymes or P-glycoprotein (P-gp) substrates within 28 days or 5 half-lives (whichever is longer) prior to the first dose of IMPs;
• Used prescription or over-the-counter (OTC) drugs (with the exception of hormonal contraception, menopausal hormone replacement therapy or occasional analgesics such as Paracetamol \[1 g per dose and maximum 2-4 g per day\], Ibuprofen and standard daily vitamins etc. in short term at the Investigator's discretion), within 14 days or 5 half-lives (whichever is longer) prior to the first dose of IMPs;
• Participated in any other investigational trials or has been exposed to other investigational drugs within 28 days or 5 half-lives of the previously administered investigational drug, whichever is longer, prior to the first dose of IMPs;
• Smoking ≥ 5 cigarettes per day (or an equivalent amount of any other nicotine-containing products) within 6 months before screening or unable to stop smoking during the study;
• Alcohol consumption of \> 21 units per week for males and \> 14 units per week for females within the 6 months before screening (1 unit=360 mL of beer or 45 mL of spirits with an alcohol content of ≥ 40% or 150 mL of wine) or a positive result of alcohol breath test on admission or unable to abstain from consuming alcohol from 24 h prior to admission, until completion of the end of study (EOS) visit;
• History of drug abuse within the 12 months before screening or a positive result of drug abuse test at screening;
• Consumption of any nutrients known to modulate cytochrome P450 enzymes or P-gp substrates activity (eg, grapefruit, pomelo, mango, star fruit, Seville \[blood\] orange products, caffeine or xanthine-containing food or beverages) within 72 h before the first dose of IMPs;
• Clinically significant laboratory abnormalities, as determined by the Investigator, including but not limited to (If the results are beyond the normal range or significantly changed, the investigator deems it necessary to repeat the measurement, vital signs and 12-Lead ECG may be repeated twice, clinical laboratory tests \[hematology, urinalysis, biochemistry and coagulation function test\] may be repeated once):
• Systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg after 5 minutes of supine rest;
• Supine resting bradycardia (pulse heart rate \[HR\] \<40 bpm) or a supine resting tachycardia (HR \>100 bpm);
• A corrected QT (QTc) interval of \> 450 ms for males and \> 470 ms for females (Fridericia's method);

Sponsors & Collaborators

• Zhejiang Vimgreen Pharmaceuticals, Ltd.: lead
• Tigermed Consulting Co., Ltd: collaborator

Study Sites (1)

Linear Clinical Research Ltd

Nedlands, Western Australia, 6009, Australia

RECRUITING

Central Study Contacts

Dr. Ana Liza Sun

CONTACT

+61 8 6382 5100; asun@linear.org.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Eligible subjects will be sequentially enrolled cohort by cohort. In each cohort, subjects will be randomized to receive VG290131 or matching placebo, respectively.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of three parts: a single ascending dose (SAD) part, a multiple ascending dose (MAD) part and a food effect (FE) part. The FE study is incorporated as part of the SAD study. Approximately 86 subjects will be enrolled in the study. SAD+FE study: 6 cohorts (1, 5, 25, 50, 100, and 200 mg), 8 subjects in each cohort, except that there are 14 subjects in the 5 mg cohort, which is the FE study cohort. MAD study: 4 cohorts (1, 5, 25, and 100 mg), 8 subjects in each cohort.

Study Record Dates

• First Submitted: September 30, 2023
• First Posted: October 13, 2023
• Study Start: October 20, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: July 26, 2024

Record last verified: 2024-07

Locations

AU (1)