Healhty
Conditions
Keywords
G01 Eye Drops, phase I
Brief summary
The primary objective of this study is to assess the safety and tolerability of single and multiple ascending doses of G01 when administered as eye drops in healthy subjects.
Detailed description
This is a Phase I, randomised, double-masked, placebo-controlled study of G01 Eye Drops in healthy male and female subjects. This study comprises a single ascending dose part (single ocular application of two drop) and a multiple ascending dose part (two drop three times daily for seven consecutive days). Three ascending dose levels will be included in both parts. In both the single and multiple ascending dose parts, each ascending cohort will enroll 6 subjects receiving G01 Eye Drops and 2 subjects receiving placebo.
Interventions
DRUGG01 Eye Drops 100 µg/mL SAD
all subjects received two 33-μL drops of G01 Eye Drops at an appropriate concentration in the study eye according to the randomisation list to achieve the required dose level
DRUGG01 Eye Drops 200 µg/mL SAD
All subjects received two 33-μL drops of G01 Eye Drops at an appropriate concentration in the study eye according to the randomisation list to achieve the required dose level
DRUGG01 Eye Drops 400 µg/mL SAD
All subjects received two 33-μL drops of G01 Eye Drops at an appropriate concentration in the study eye according to the randomisation list to achieve the required dose level
DRUGG01 Eye Drops 100 µg/mL MAD
All subjects receive two 33-μL drops of G01 Eye Drops at the predefined concentration in the study eye according to the randomisation list to achieve the required dose level, which is administered three times daily (morning, midday, and bedtime) for six consecutive days from Day 1 to Day 6, with only one single morning instillation on Day 7.
DRUGG01 Eye Drops 200 µg/mL MAD
All subjects receive two 33-μL drops of G01 Eye Drops at the predefined concentration in the study eye according to the randomisation list to achieve the required dose level, which is administered three times daily (morning, midday, and bedtime) for six consecutive days from Day 1 to Day 6, with only one single morning instillation on Day 7.
DRUGG01 Eye Drops 400 µg/mL MAD
All subjects receive two 33-μL drops of G01 Eye Drops at the predefined concentration in the study eye according to the randomisation list to achieve the required dose level, which is administered three times daily (morning, midday, and bedtime) for six consecutive days from Day 1 to Day 6, with only one single morning instillation on Day 7.
DRUGPlacebo of G01 Eye Drops SAD
All subjects receive two 33-μL drops of G01 Eye Drops Placebo in the study eye according to the randomisation list
DRUGPlacebo of G01 Eye Drops MAD
All subjects receive two 33-μL drops of G01 Eye Drops Placebo in the study eye according to the randomisation list , which is administered three times daily (morning, midday, and bedtime) for six consecutive days from Day 1 to Day 6, with only one single morning instillation on Day 7.
Sponsors
Qingdao WanMing BioCell Pharmaceutics Co.,Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double-masked study. All participants, care providers, investigators and outcome assessors are masked to the treatment assignment throughout the study period to avoid assessment bias. The investigational product and placebo are identical in appearance, color and packaging
Intervention model description
This is a single-center, sequential dose-escalation study consisting of single ascending dose (SAD) and multiple ascending dose (MAD) parts. Eligible healthy subjects are enrolled in sequential dose cohorts with fixed drug-placebo allocation ratio to evaluate safety, tolerability and pharmacokinetics of G01 Eye Drops.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults aged 18 to 50 years (inclusive) at the time of signing the informed consent form, of either sex. * Body weight ≥50 kg for males and ≥45 kg for females at screening; body mass index (BMI) within the range of 19.0 to 28.0 kg/m² (inclusive), calculated as body weight (kg) / height² (m²); vital signs, laboratory tests, and physical examination findings are either within normal limits or deemed clinically insignificant (abnormal without clinical relevance). * Best-corrected visual acuity (BCVA) ≥83 letters in both eyes (with refractive error ≤ -6.0 D); intraocular pressure (IOP) between 10 and 21 mmHg (inclusive) in both eyes, with an interocular IOP difference \<5 mmHg; ophthalmic examinations in both eyes (including BCVA, IOP, pupillary function, extraocular muscle motility, slit-lamp biomicroscopy, corneal fluorescein staining, and funduscopy after mydriasis) show no abnormalities, or any abnormalities present are clinically insignificant. * Ability and willingness to provide written informed consent, dated and signed personally, and to comprehend the study procedures and comply with all protocol requirements. * Agreement to practice effective contraception from the time of signing informed consent through 3 months after the last dose of study drug, and no plan to donate sperm or ova during this period.
Exclusion criteria
* Women who are pregnant or lactating. * History or presence of severe disorders of the cardiovascular, respiratory, hepatobiliary, digestive, urinary, renal, endocrine, immune, metabolic, or neuropsychiatric systems, or history of malignancy. * Anatomical abnormality in either eye or monocular vision; or any eyelid, ocular surface, or lacrimal drainage system abnormality deemed by the investigator to potentially affect drug absorption. * History of ocular disease in either eye that could affect visual function (e.g., glaucoma, retinal detachment, etc.), and considered by the investigator as unsuitable for trial participation. * Infectious, immune-mediated, or inflammatory ocular disease, or ocular trauma affecting either eye within 3 months prior to the first dose. * Clinically significant findings on ophthalmic examination at screening (e.g., conjunctival hyperemia grade ≥1, \>2 punctate corneal fluorescein staining spots, tear film break-up time \[TBUT\] \<10 seconds in both eyes, or other chronic or acute ocular pathologies). * History of intraocular surgery or ocular laser therapy. * Use of any ophthalmic medication (including eye drops or ophthalmic gels, etc.) within 1 month prior to screening. * Contact lens wear within 14 days prior to screening or during the clinical study period. * Positive test results at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus (HIV) antibody/antigen, or syphilis serology. * History of drug allergy, particularly known allergy or idiosyncratic reaction to the investigational product or to any concomitant medications used during the study procedures. * Inability to tolerate venipuncture and/or history of vasovagal syncope (hemophobia or trypanophobia). * Prior treatment with any other nerve growth factor (NGF)-class agents; use of immunosuppressants or any other prescription medications within 4 weeks prior to the start of the study; use of traditional Chinese medicines, Chinese patent medicines, over-the-counter drugs, or dietary supplements within 2 weeks prior to the start of the study. (For drugs with a long half-life, a washout period of at least 5 half-lives is required.) * Participation in any other interventional clinical trial within 3 months prior to screening. * Vaccination within 1 month prior to screening, or planned vaccination during the study period. * Major surgery within 6 months prior to screening, or planned surgery during the study period. * History of drug abuse, positive urine drug screen, or current substance dependence. * Non-physiological blood loss ≥400 mL (including trauma, phlebotomy, or blood donation) within 3 months prior to the study, or receipt of any blood product transfusion; or blood donation within 3 months or planned blood donation during the study period; or blood sampling as a subject in another study within 3 months. * Average daily cigarette consumption \>5 cigarettes per day within 3 months prior to screening, or inability to refrain from smoking throughout the entire study period. * Suspected or confirmed alcohol dependence; average daily alcohol intake exceeding 2 units per day within 3 months (1 unit = 10 mL of pure ethanol, equivalent to 200 mL of beer at 5% alcohol, 25 mL of spirits at 40% alcohol, or 83 mL of wine at 12% alcohol); or positive alcohol breath test; or inability to abstain from alcohol during the study period. * Vital signs outside the following ranges: systolic blood pressure \<90 mmHg or ≥140 mmHg; diastolic blood pressure \<50 mmHg or ≥90 mmHg; pulse rate \<50 bpm or \>100 bpm. * Any other condition that, in the opinion of the investigator, would render the subject unsuitable for participation in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From informed consent through post-study visit, up to Day 14 for single-administration cohorts and multiple-administration cohorts | The number and percentage of participants with adverse events will be summarized by treatment group. Adverse events will be evaluated for seriousness, severity, relationship to study drug, action taken, outcome, and classification as treatment-emergent adverse events (TEAEs). |
| Number of Participants With Clinically Significant Abnormalities in Safety Assessments | From baseline through post-study visit, up to Day 14 for single-administration cohorts and multiple-administration cohorts | Safety assessments include vital signs, physical examinations, 12-lead electrocardiograms, clinical laboratory tests, ocular symptom assessments, and ophthalmic examinations. The number and percentage of participants with clinically significant abnormali |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentration of G01 Eye Drops | Day 1, Day 2, Day 3 for single-administration cohorts; Day 1, Day 5, Day 6, Day 7, Day 8, Day 9 for multiple-administration cohorts | Serum drug concentrations of G01 Eye Drops will be measured and analyzed to characterize the serum concentration profiles in single-administration and multiple-administration cohorts. Blood samples for concentration analysis will be collected at scheduled time points throughout the study period. The scheduled sampling time points may be adjusted appropriately according to the actual detection results during the study. |
| Number of Participants With Positive Anti-Drug Antibody (ADA) | Day 1, Day 3, Day 14 for single-administration cohorts; Day 1, Day 8, Day 14 for multiple-administration cohorts | Blood samples will be collected at scheduled time points to detect anti-drug antibody (ADA) against G01 Eye Drops. The number and percentage of participants with positive ADA results will be summarized in single-administration and multiple-administration cohorts to evaluate the immunogenicity of G01 Eye Drops. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYuzhong Wang
Affiliated Hospital of Jining Medical University
Outcome results
None listed