Clinical trial NCT05227768: Safety and Pharmacokinetics Study of Single Ascending Doses of VV116 in Healthy Volunteers
Official title: A Dose-escalation, Single-center, Randomized, Double-blinded, Placebo-controlled, Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profiles of VV116 Administered Orally to Chinese Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: VV116
Phase I
dose-escalation
Tolerability
Pharmacokinetic
Lead sponsor: Vigonvita Life Sciences
Sponsor class: INDUSTRY
First posted: 2022-02-07
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The study consists of 5 dose groups, starting at 25 mg, 6 subjects in 25 mg group, and 8 subjects in each other group (male or female), randomly assigned to study drug or placebo group to evaluate the safety, tolerability and PK characteristics. The subject number of single dose group may increase or decrease depending on the safety and PK data obtained. The dose levels are planned at 25 mg, 200 mg, 400 mg, 800 mg and 1200 mg. Based on observed tolerability and safety data or obtained PK data, adjustments are allowed at all dose levels in the clinical trial.

Detailed description: 4 subjects in the 25 mg dose group will receive VV116 tablets and the other 2 subjects will receive placebo. In other dose groups, 6 subjects in each group will receive VV116 tablets and 2 subjects will receive placebo. 25mg,800mg and 1200 mg dose group will be given by sentinel administration (i.e. 1 study drug, 1 placebo). Subjects who receive sentinel administration will be observed for 48 hours and investigator will evaluate the safety parameters (including symptoms, vital signs, physical examination, etc.).

Eligibility criteria: Inclusion Criteria:

1. Healthy subjects between the ages of 18 and 45 years;
2. Body weight no less than 50 kg for male, no less than 45 kg for female; Body Mass Index of 19 to 26kg/m2;
3. Physical examination, vital signs examination, laboratory examination, ECG, B-ultrasound and fundus examination results were normal or abnormal without clinical significant;
4. Subjects who are willing to take proper contraceptive during the study and within 3 months after the study completed;
5. Subjects who are able to understand and follow study plans and instructions; Subjects who have voluntarily decided to participate in this study, and signed the informed consent form;

Exclusion Criteria:

1. Subjects with hypersensitivity to VV116 or any of the excipients;
2. Subjects with allergic diseases or allergic constitution;
3. Subjects with central nervous system,cardiovascular system,gastrointestinal, respiratory system,urinary,Hematologic System,metabolic disorders that require medical intervention or other diseases (such as psychiatric history) that are not suitable for clinical trials;
4. Blood donation or blood loss ≥ 400 mL within 3 months prior to inclusion, or have a history of blood product use history;
5. Participated in a clinical study involving another investigational drug within 3 month before the screening visit;
6. Taken any prescription drugs, non-prescription drugs, Chinese herbal medicine or health care products within 2 weeks prior to screening;
7. Drug or alcohol addicts within 1 year prior to screening, who drink at least twice a day or more than 14 units per week, or who are addicted to alcohol (1 unit ≈200 mL beer with 5% alcohol content, 25 mL spirits with 40% alcohol content or 85 mL wine with 12% alcohol content) ;
8. Those who smoke more than 10 cigarettes per day and do not agree to avoid using any tobacco products during the trial period;
9. Those who cannot quit smoking or drinking during the trial;
10. Those who are positive for hepatitis B surface antigen (HBsAg), HCV antibody, syphilis antibody and HIV antibody;
11. Abnormal and clinically significant chest radiographs (anteroposterior);
12. B ultrasound examination showed moderate to severe fatty liver;
13. Pregnant or lactating women or male subjects whose spouse has a child care plan within 3 months;
14. The investigator believes that there are other factors that are not suitable for participating in this trial.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 7 days after treatment
measure: Tmax
timeFrame: From time zero up to 48 hours post-dose following oral administration of VV116
measure: Cmax
timeFrame: From time zero up to 48 hours post-dose following oral administration of VV116
measure: AUC0~t
timeFrame: From time zero up to 48 hours post-dose following oral administration of VV116
measure: AUC0-∞
timeFrame: From time zero up to 48 hours post-dose following oral administration of VV116
Secondary outcomes:
measure: structural of metabolites
timeFrame: From time zero up to 72 hours post-dose following oral administration of VV116
measure: Ae(total excretion of kidney)
timeFrame: From time zero up to 72 hours post-dose following oral administration of VV116
measure: Ae%(proportion of excretion of kidney)
timeFrame: From time zero up to 72 hours post-dose following oral administration of VV116
measure: CLr(renal clearance rate)
timeFrame: From time zero up to 72 hours post-dose following oral administration of VV116
measure: Cumulative excretion and percentage of VV116 and major metabolites in feces.
timeFrame: From time zero up to 72 hours post-dose following oral administration of VV116
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Xuhui Central Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Xuhui Central Hospital
name: Gangyi Liu
role: PRINCIPAL_INVESTIGATOR
References: